Chorismate pathway metabolite compositions and methods of use thereof

Abstract

Disclosed herein are compositions (e.g., pharmaceutical compositions, nutraceutical compositions) and methods useful for, inter alia, modulating levels of certain chorismate metabolites in a subject (e.g., in the gut of a subject). Modulation of levels of certain chorismate metabolites in a subject (e.g., levels of the chorismate metabolites in the gut) may have beneficial effects, prophylactic, and / or therapeutic effects for the subject, for example, in enhancing cognitive function or treating one or more signs or symptoms of a neurological disorder.

Description

[0001] PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0002] CHORISMATE PATHWAY METABOLITE COMPOSITIONS AND METHODS OF USE THEREOF

[0003] RELATED APPLICATIONS

[0004] This application claims the benefit under 35 U.S.C. § 119(e) of US Provisional Application No. 63 / 686,692, filed August 23, 2024 entitled “CHORISMATE PATHWAY METABOLITE COMPOSITIONS AND METHODS OF USE THEREOF”, the content of which is hereby incorporated by reference herein in its entirety for all purposes.

[0005] BACKGROUND

[0006] The gut-brain axis , a term referring to bidirectional communication between the gastrointestinal (GI) tract and the central nervous system (CNS), has been increasingly implicated in a wide range of diseases and disorders in humans, including both GI disorders and CNS disorders. Similarly, the gut microbiome, an important contributor to GI function, may have a role in neurological function (e.g., neurological disorders, cognitive functions) via its interactions with the gut-brain axis. Accordingly, compositions and methods targeting the gut and / or gut microbiome of a subject may have beneficial effects on numerous neurological functions and / or be useful for preventing or treating a disease (e.g., a neurological disease).

[0007] SUMMARY

[0008] Systematic meta-analyses of studies profiling the gut microbiome of individuals with autism spectrum disorder (ASD) have revealed that certain metabolites of chorismate-associated pathways in the gut microbiome are commonly deficient in individuals with ASD relative to neurotypical individuals. Modulation of levels of these chorismate metabolites in a subject (e.g., levels of the chorismate metabolites in the gut) and, optionally, additional active ingredients, may have beneficial effects and / or therapeutic effects for the subject, for example, in improving socialization capabilities, reducing anxiety, reducing repetitive behaviors, improving cognitive function, and / or treating one or more signs or symptoms of ASD. Described herein are compositions (e.g., pharmaceutical compositions) and formulations comprising chorismate metabolites, and methods of use thereof.

[0009] Aspects of the disclosure relate to compositions (e.g., pharmaceutical compositions, nutraceutical compositions) comprising one or more molecules associated with a chorismate metabolic pathway. In some aspects, provided herein are compositions (e.g., pharmaceutical PCT / US25 / 43182 22 August 2025 (22.08.2025) compositions, nutraceutical compositions) comprising a predetermined amount of two or more metabolites of a chorismate pathway. In some embodiments, the predetermined amount is an effective amount. In some embodiments, a composition (e.g., pharmaceutical composition, nutraceutical composition) comprises an additional active ingredient.

[0010] Aspects of the disclosure relate to compositions (e.g., pharmaceutical compositions, nutraceutical compositions) comprising a predetermined amount (e.g., an effective amount) of at least one chorismate metabolite and an effective amount of an additional active ingredient.

[0011] In some embodiments, the at least one chorismate metabolite is Vitamin K2, L- tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, choline, folinic acid (5- MFHP), or a combination thereof. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises 2 or more chorismate metabolites. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises 3 or more chorismate metabolites. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises 4 or more chorismate metabolites. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises 5 or more chorismate metabolites. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP). In some embodiments, the chorismate metabolites (e.g., the Vitamin K2, L-tryptophan, 5-HTP, L-tyrosine, L-phenylalanine, and 5-MFHP) are present in the composition (e.g., pharmaceutical composition, nutraceutical composition) in a pre-determined molar ratio.

[0012] In some embodiments, the at least one chorismate metabolite is one or more aromatic amino acids. In some embodiments, the one or more aromatic amino acids are L-tryptophan, L- tyrosine, L-phenylalanine, or a combination thereof. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises 2 or more aromatic amino acids, e.g., L-tryptophan and L-tyrosine; L-tryptophan and L-phenylalanine; or L-tyrosine and L-phenylalanine. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises L-tryptophan, L-tyrosine, and L-phenylalanine. In some embodiments, the aromatic amino acids are present in the composition (e.g., pharmaceutical composition, nutraceutical composition) in a pre-determined molar ratio.

[0013] In some embodiments, the at least one chorismate metabolite is one or more aromatic amino acids, and does not comprise another amino acid. In some embodiments, the one or more aromatic amino acids are L-tryptophan, L-tyrosine, L-phenylalanine, or a combination thereof, PCT / US25 / 43182 22 August 2025 (22.08.2025) and does not compnse another amino acid. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises 2 or more aromatic amino acids, e.g., L-tryptophan and L-tyrosine; L-tryptophan and L-phenylalanine; or L-tyrosine and L-phenylalanine, and does not comprise another amino acid. In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises L- tryptophan, L-tyrosine, and L-phenylalanine, and does not comprise another amino acid. In some embodiments, the aromatic amino acids are present in the composition (e.g., pharmaceutical composition, nutraceutical composition) in a pre-determined molar ratio, and no other amino acids are present.

[0014] In some embodiments, the additional active ingredient is a therapeutic agent.

[0015] In some embodiments, the additional active ingredient comprises an amino acid (e.g., a non-aromatic amino acid). In some embodiments, the amino acid is L-carnosine. In some embodiments, the additional active ingredient comprises riboflavin (e.g., Vitamin B2). In some embodiments, the additional active ingredient comprises Vitamin D3.

[0016] In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises a carrier. In some embodiments, the carrier comprises a polymer that is not absorbed in a gastrointestinal tract. In some embodiments, the carrier comprises polyvinylpyrrolidone. In some embodiments, the chorismate metabolite and additional active ingredient are loaded into the carrier.

[0017] In some embodiments, the composition (e.g., pharmaceutical composition, nutraceutical composition) comprises a substance that facilitates a targeted delivery of the chorismate metabolite, the additional therapeutic agent, and the carrier to an intestinal location. In some embodiments, the substance comprises a first material that dissolves at a pH between about 6.0 and about pH 7.6. In some embodiments, the first material dissolves at a pH 7.5. In some embodiments, the substance comprises a second material that is susceptible to degradation by a microbial organism. In some embodiments, the second material is susceptible to degradation by a microbial organism present in a large intestine of a subject. In some embodiments, the second material is susceptible to degradation by a microbial organism present in a colon of a subject. In some embodiments, the substance comprises a first material that dissolves at a pH between about pH 6.0 and about pH 7.6 and a second material that is susceptible to degradation by a microbial organism present in a large intestine of a subject.

[0018] In some embodiments, the substance comprises a scaffold. In some embodiments, the scaffold comprises a first material that dissolves at a pH between about 6.0 and about pH 7.6. PCT / US25 / 43182 22 August 2025 (22.08.2025) and a second material of the substance comprises a second material that is susceptible to degradation by a microbial organism.

[0019] In some embodiments, the substance comprises one or more layers. In some embodiments, a first layer of the substance comprises a first material that dissolves at a pH between about 6.0 and about pH 7.6. and a second layer of the substance comprises a second material that is susceptible to degradation by a microbial organism.

[0020] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition) comprising a core comprising an effective amount of at least one chorismate metabolite; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered. In some embodiments, the at least one chorismate metabolite comprises one or more aromatic amino acids (e.g., L- tryptophan, L-tyrosine, L-phenylalanine).

[0021] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition) comprising: a core comprising an effective amount of at least one chorismate metabolite and an effective amount additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered. In some embodiments, the at least one chorismate metabolite comprises one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L-phenylalanine).

[0022] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition) comprising: a core comprising an effective amount of two or more chorismate metabolites; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered. In some embodiments, the two or more chorismate metabolites comprise one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L-phenylalanine).

[0023] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of L-carnosine; and an effective amount of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, or folinic acid (5-MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is PCT / US25 / 43182 22 August 2025 (22.08.2025) configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0024] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of L-carnosine; and an effective amount of one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L- phenylalanine); and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0025] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of riboflavin; and an effective amount of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, or folinic acid (5-MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0026] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of riboflavin; and an effective amount of one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L- phenylalanine); and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0027] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of Vitamin B2; and an effective amount of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, or folinic acid (5-MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0028] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of Vitamin B2; and an effective amount of one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L- phenylalanine); and a controlled release coating applied to an exterior surface of the core, PCT / US25 / 43182 22 August 2025 (22.08.2025) wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0029] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of Vitamin D3; and an effective amount of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, or folinic acid (5-MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0030] Aspects of the disclosure relate to a composition (e.g., pharmaceutical composition, nutraceutical composition), comprising: a core comprising: an effective amount of Vitamin D3; and an effective amount of one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L- phenylalanine); and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is administered.

[0031] In some embodiments, a composition contemplated herein is a pharmaceutical composition. In some embodiments, a composition contemplated herein is a nutraceutical composition.

[0032] Further aspects of the disclosure relate to methods comprising providing (e.g., administering, applying) a composition (e.g., pharmaceutical composition, nutraceutical composition) described herein to a subject.

[0033] In some embodiments, the subject has or is suspected of having a neurological disorder. In some embodiments, the subject has or is at risk of developing a neurological disorder (e.g., a neurodevelopmental disorder). In some embodiments, the subject has or is at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, a gastrointestinal disorder, an anxiety disorder, depression, or an eating disorder. In some embodiments, the subject has or is at risk of developing ASD. In some embodiments, the subject is neurotypical.

[0034] In some embodiments, the subject has been determined to have an altered level of one or more chorismate metabolites relative to a level of the same chorismate metabolites in a neurotypical individual. In some embodiments, the altered level is determined from a sample of the subject. In some embodiments, the sample of the subject is a fecal sample. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0035] Aspects of the disclosure relate to a method of treating a subject having or at risk of developing autism spectrum disorder, the method comprising administering to the subject a pharmaceutical composition, the pharmaceutical composition comprising a core comprising: an effective amount of at least one chorismate metabolite and an effective amount of an additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

[0036] Aspects of the disclosure relate to a method of preventing a subject from developing autism spectrum disorder, the method comprising administering to the subject a pharmaceutical composition, the pharmaceutical composition comprising a core comprising: an effective amount of at least one chorismate metabolite and an effective amount of an additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

[0037] In some embodiments, the method comprises a step of determining that the subject has an altered intestinal level of one or more chorismate metabolites relative to a neurotypical individual, wherein the determining occurs prior to the administering.

[0038] Aspects of the disclosure relate to a method of treating a subject determined to have an altered intestinal level of one or more chorismate metabolites relative to a neurotypical individual, the method comprising administering to the subject a pharmaceutical composition, the pharmaceutical composition comprising a core comprising: an effective amount of at least one chorismate metabolite and an additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

[0039] Aspects of the disclosure relate to a method of treating a subject determined to have an altered intestinal level of one or more chorismate metabolites relative to a healthy individual, the method comprising administering to the subject a pharmaceutical composition, the pharmaceutical composition comprising a core comprising: an effective amount of at least one chorismate metabolite and an additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered. In some embodiments, the altered intestinal level PCT / US25 / 43182 22 August 2025 (22.08.2025) of one or more chonsmate metabolites is associated with dysbiosis (e.g., a disruption to the microbiome). In some embodiments, the altered intestinal level of one or more chorismate metabolites is associated with an inflammatory state (e.g., an inflammatory condition). In some embodiments, the altered intestinal level of one or more chorismate metabolites is associated with cancer (e.g., a glyphosate-associated cancer). Accordingly, these compositions may be useful for treating dysbiosis, inflammatory state, and / or cancer, in addition to other neurological conditions described herein.

[0040] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention. In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control.

[0041] BRIEF DESCRIPTION OF THE DRAWINGS

[0042] FIG. 1 shows a schematic illustration of the shikimate pathway and a possible effect of glyphosate exposure on the same.

[0043] FIG. 2 shows a schematic illustration of simplified chorismate metabolic pathways. Chorismate can be metabolized, inter alia, into aromatic amino acids (e.g., phenylalanine, tyrosine, tryptophan), folate, siderophores (e.g., enterobactin), or ubiquinols and menaquinols (e.g., coenzyme Q).

[0044] FIG. 3A-3D show that chorismate-related pathways, enzymes and molecules are frequently altered in autism spectrum disorder (ASD). FIG. 3A shows the most commonly altered microbial pathways in ASD cohorts. Log2(ASD / Control) fold-change and cohort- level significance (number of cohorts with rank sum FDR P<0.05) for predicted Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) pathways in 16S cohorts are shown. FIG. 3B show chorismate-related pathway enrichment via meta- analysis approaches. Pathways are ranked by the frequency of statistical differences, categorized by relation to chorismate subpathways, and analyzed via gene-set enrichment. A heatmap summarizes the normalized enrichment score (NES), with asterisks indicating significance (**** q < 0.0001, *** q < 0.001, ** q < 0.01, * q < 0.05). FIG. 3C shows age and sex-adjusted metabolite abundances, displayed as normalized enrichment score (NES) across different inclusion thresholds for imputed molecule abundances, ranging from 0.1 (where only molecules quantified in at least 90% of samples are included) to 1 (where all molecules are analyzed PCT / US25 / 43182 22 August 2025 (22.08.2025) regardless of missing values in the pre-quantile normalized data). Asterisks indicate significance levels for chorismate subpathway enrichment among ASD-associated metabolites (. FDR q<0.1, * FDR q<0.05, ** FDR q<0.01, **** FDR q=0). FIG. 3D shows association of chorismate- derived metabolites and ASD behavioral categories (SRS) ranked by the number of correlated behaviors (dot fill: ordinal regression coefficients; dot size: P<0.01). AAA - aromatic amino acids. SCI - Social Communication and Interaction. RRB - Restricted Interests and Repetitive Behavior.

[0045] FIGs. 4A-4N show chorismate-derived metabolites in stool and their associations to ASD. Subject-averaged quantile-normalized abundance of each metabolite is shown with boxplots illustrating the mean and inter-quartile range (IQR) of controls + normally communicating ASD individuals; and ASD individuals with mild-severe communication symptoms. FIG. 4A Tetrahydrofolic acid; FIG. 4B L-tyrosine; FIG. 4C L-tryptophan; FIG. 4D L-Phenylalanine, methyl ester; FIG. 4E 3-Indolepropionic acid; FIG. 4F 3-(3-Hydroxyphenyl)- propanoic acid; FIG. 4G 4-Hydroxy-phenylacetic acid; FIG. 4H p-Hydroxy-phenyllactic acid; FIG. 41 tyramine; FIG. 4J Shikimic acid; FIG. 4K Methionine; FIG. 4L Dopamine; FIG. 4M trans-Ferulic Acid; FIG. 4N Melatonin. Asterisks indicate significance from rank sum test (P<0.05). Subject group sizes of n=17 for Control-Normal scoring subjects, and n=18 for subjects with Mild-Severe scores. N.C. ASD - normally communicating ASD individuals; M. ASD - ASD individual with mild communication deficits; Mo.C. ASD- ASD individual with moderate communication deficits; S.C. ASD- ASD individual with severe communication deficits.

[0046] FIGs. 5A-5E show distant metabolites (within 22 reactions of chorismate) that are altered with ASD severity. Metabolites with the strongest correlation to ASD severity groupings by ordinal regression are displayed per severity category with individual points representing subject averages. Boxplots demonstrate mean and IQR of each severity group. Metabolites displayed obtained P<0.01. FIG. 5A (-)-Riboflavin; FIG. 5B Xanthurenic acid; FIG. 5C Hypoxanthine; FIG. 5D 1 -Methylxanthine; FIG. 5E L-Lysine. Subject group sizes include: Control n=13, Normal range n=3, Mild range n=2, Moderate range n=6, Severe range n=l 1.

[0047] FIGs. 6A-6F show effects of glyphosate and chorismate or aromatic amino acids (AAA; L-tyrosine, L-phenylalanine, and L-tryptophan) on gut microbial growth in vitro. FIG. 6A shows an experimental design for in vitro growth of bacteria for 24 hours in minimal media with Omg / mL or 5mg / mL glyphosate; intervention (chorismic acid or equimolar AAA mixture) or control. Growth is measured by ODeoo nm (mean ± s.e.m.) and collected over 2 days with 3 PCT / US25 / 43182 22 August 2025 (22.08.2025) replicates per day. FIG. 6B shows hourly growth rescue from glyphosate by lOpg / mL or 200pg / mL chorismic acid measured in aerobically grown E. coli ATCC25922. FIG. 6C shows growth rescue from glyphosate in aerobically grown E. coli ATCC25922 with 844pM or 44.2pM chorismic acid, normalized to control groups growing without glyphosate or intervention. FIG. 6D shows growth rescue from glyphosate in anaerobically grown B. theta VPI 5482 (ATCC 29741) with 422pM or 44.2pM chorismic acid, normalized to control groups growing without glyphosate or intervention. FIG. 6E shows growth rescue from glyphosate in aerobically grown E. coli ATCC25922 with lOOpM or 6.25pM AAA mixture, normalized to control groups growing without glyphosate or intervention. FIG. 6F shows growth rescue from glyphosate in anaerobically grown B. theta VPI 5482 (ATCC 29741) with 500pM or 125pM AAA, normalized to control groups growing without glyphosate or intervention. Asterisks in FIGs. 6C-6F indicate significance from 2-way ANOVA adjusted for multiple comparisons (* P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001).

[0048] FIGs. 7A-7F show effects of chorismic acid treatment on chorismate-derived metabolites in mice. FIG. 7A shows an experimental design for in vivo chorismic acid treatment in mice. Wildtype mice were treated with high, medium, or low amounts of chorismic acid via gavage (high- 1.766 mg / ml, medium - 0.176 mg / ml, low- 0.017 mg / ml) or drinking water (high- 0.111 mg / ml, medium-0.011 mg / ml, low- 0.001 mg / ml) for 1 week and fecal pellets were collected for analysis. FIG. 7B shows effects of chorismate exposure via drinking water on gentisic acid, paxilline, L-tyrosine, 3-dehydroshikimic acid, L-tryptophan, and trans-ferulic acid); FIGs. 7C shows effects of chorismate exposure via gavage on xanthine, hypoxanthine, beta-Cyano-L-alanine, and beta-Nicotinamide mononucleotide; FIGs. 7D shows effects of chorismate exposure via gavage on hypoxanthine, trans-ferulic acid, L-lysine, and D- pyroglutamic acid. FIGs. 7E shows effects of chorismate exposure via gavage on 4- hydroxybenzoic acid and N-Acetylneuraminic acid. FIG. 7F is a bubble plot showing the Log2(fold-change) of 15 chorismate-derived metabolites that are depleted in ASD [human] individuals (left; ASD / control) but are enriched by chorismate treatment in mice (right; after / before treatment). Dot size reflects statistical significance (rank sum P<0.05). For FIGs. 7C-7E, numbers in metabolite names (e.g., “_1”) indicate separate metabolites of the same annotation.

[0049] FIGs. 8A-8E show effects of chorismic acid treatment on ASD-like behaviors in four mouse models of ASD. FIG. 8A shows an experimental design for chorismate intervention in wildtype mice (“WT”), BTBR T+Itpr3tf / J mouse (“BTBR”), offspring of female mice exposed PCT / US25 / 43182 22 August 2025 (22.08.2025) to valproic acid during pregnancy ( ‘VPA ), and offspring of female mice exposed to glyphosate during pregnancy (“Glyphosate”). On P21, mice are treated with chorismic acid, shikimate, or a vehicle, then assessed for ASD-like behaviors on P56. FIG. 8B shows effects of chorismate treatment on social interaction ratio in a 3-chamber sociability test (permutation test: P=0.0013; n=41 for vehicle, n=41 for chorismate-treated). FIG. 8C shows effects of chorismate treatment on percent time in open arms in an elevated plus maze (permutation test: P=0.0284; n=32 for vehicle, n=32 for chorismate-treated). FIG. 8D shows effects of chorismate treatment on marbles buried during a marble burying test (permutation test: P=0.0565; n=32 for vehicle, n=32 for chorismate-treated); higher values indicate reduced repetitive behaviors. FIG. 8E shows effects of chorismate treatment on frequency of nose-to-nose interaction during reciprocal social interaction test (permutation test: P=0.0202; n=32 for vehicle, n=32 for chorismate-treated). All quantifications compare control and ASD-like mice treated with either vehicle or chorismate or shikimate. All data are reported as mean ± s.e.m.

[0050] DETAILED DESCRIPTION

[0051] Chorismate, the anionic form of chorismic acid, refers to a branch point metabolite produced by chorismate synthase of the shikimate pathway. Though produced by microorganisms and plants, but not animals, chorismate is a precursor for the biosynthesis of several important compounds in animals, such as aromatic amino acids (e.g., phenylalanine, tryptophan, tyrosine), indoles, folate, ubiquinol, and menaquinol. Chorismate is produced by many microorganisms, including many of those commonly found in the human gastrointestinal (GI) tract as part of the gut microbiome. Because of the absence of the shikimate pathway in humans, the levels of each molecule along the shikimate pathway, as well as the pathways dependent on chorismate, are dependent on either the amount of each molecule being taken in through diet or the amount produced by gut microorganisms.

[0052] Increasing evidence indicates that the gut microbiome may exert influence on brain physiology and mental functions (e.g., cognitive function) via the gut-brain axis. Indeed, profiling of the gut microbiome of individuals with autism spectrum disorder (ASD) (e.g., as described in WO 2023 / 159225 A2, hereby incorporated by reference in its entirety) has revealed that levels of microorganisms comprising chorismate-associated pathways (e.g., shikimate pathway, chorismate metabolism) are commonly deficient in the gut of individuals with ASD relative to levels in neuro typical individuals. While efforts to influence neurological and / or PCT / US25 / 43182 22 August 2025 (22.08.2025) cognitive function via the gut-brain axis have largely focused on modulation of the microbiota content of the gut microbiome (e.g., probiotics, prebiotics), the inventors have discovered that modulation of levels of chorismate metabolites (e.g., chorismate precursors, products of chorismate metabolism) may have beneficial effects and / or therapeutic effects for subjects, for

[0053] 5 example, improving cognitive function or treating one or more signs or symptoms of ASD.

[0054] Thus, provided herein, in some aspects, are compositions and formulations comprising certain chorismate metabolites, and methods of use thereof.

[0055] Superpathway of Chorismate Metabolism

[0056] Compositions described herein comprise chorismate metabolites. In some embodiments,

[0057] 10 a chorismate metabolite is a metabolite of the superpathway of chorismate. As used herein, “superpathway of chorismate metabolism” refers to the pathway for the production of chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate (PEP; i.e., the shikimate pathway) and the pathways for the conversion of chorismate to downstream metabolites (e.g., aromatic amino acids and their derivatives, ubiquinols, menaquinol, tetrahydrofolate,

[0058] 15 enterobactin). A non-limiting list of chorismate metabolites can be found in Table 1.

[0059] Table 1, Metabolites of the superpathway of chorismate metabolism PCT / US25 / 43182 22 August 2025 (22.08.2025) PCT / US25 / 43182 22 August 2025 (22.08.2025) PCT / US25 / 43182 22 August 2025 (22.08.2025) PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0060] Shikimate Pathway

[0061] Production of chorismate occurs through the shikimate pathway, shown in FIG. 1. In some embodiments, a chorismate metabolite is a chorismate precursor (e.g., a metabolite of the shikimate pathway). A chorismate precursor is any intermediate molecule involved in the production of chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate. The shikimate pathway comprises seven enzymatic steps: (1) 3-deoxy-D-arabino-heptulosonate-7- phosphate synthase (DAHPS) converts D-erythrose 4-phosphate (e.g., an intermediate of the pentose phosphate cycle) and phosphoenolpyruvate (e.g., an intermediate of glycolysis) to 3- deoxy-D-arabino-heptulosonate-7-phosphate (DAHP); (2) 3-dehydroquinate synthase (DHQS) converts DAHP to 3-dehydroquinate; (3) 3-dehydroquinate dehydratase (DHQ) converts 3- dehydroquinate to 3-dehydroshikimate; (4) shikimate 5-dehydrogenase (SDH) converts 3- dehydro shikimate to shikimate; (5) shikimate kinase (SK) converts shikimate to shikimate 3- phosphate; (6) 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) converts shikimate 3- phosphate to 5-O-carboxyvinyl-3-phosphoshikimate (also referred to as 5-enolpyruvylshikimate- 3-phosphate (EPSP)); and (7) chorismate synthase (CS) converts 5-O-carboxyvinyl-3- phospho shikimate to chorismate (i.e., chorismic acid). Thus, the term “chorismate precursor,” as used herein, may refer to any of D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3- dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl- 3 -pho spho shikimate .

[0062] In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises D-erythrose 4-phosphate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises phosphoenolpyruvate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises DAHP. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises 3-dehydroquinate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition comprises 3-dehydroshikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises shikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises shikimate 3-phosphate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises 5-O-carboxyvinyl-3-phosphoshikimate.

[0063] In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3- PCT / US25 / 43182 22 August 2025 (22.08.2025) dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl-

[0064] 3-phosphoshikimate, or any combination thereof. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises two more of D-erythrose

[0065] 4-phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl-3-phosphoshikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises three or more of D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3- dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl-3- phospho shikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises four or more of D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3- phosphate, and 5-O-carboxyvinyl-3-phosphoshikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises five or more of D- erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl-3-phosphoshikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises six or more of D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3- dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl- 3 -phospho shikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises seven or more of D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3- phosphate, and 5-O-carboxyvinyl-3-phosphoshikimate. In some embodiments, a composition (e.g., nutraceutical composition or pharmaceutical composition) comprises D-erythrose 4- phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-carboxyvinyl-3-phosphoshikimate.

[0066] Chorismate Pathway

[0067] Chorismate can be transformed into several biologically relevant aromatic molecules, including but not limited to aromatic amino acids (e.g., phenylalanine, tyrosine, tryptophan) and their derivatives, folate, and its derivatives (e.g., tetrahydrofolate), siderophores (e.g., enterobactin), ubiquinols (e.g., coenzyme Q), and menaquinol. FIG. 2 shows an exemplary representation of five chorismate-dependent pathways. In some embodiments, a chorismate metabolite comprises a product of a chorismate metabolic pathway. As used herein, a PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0068] ‘chonsmate metabolic pathway refers to a pathway within the pathway of chonsmate metabolism. As used herein, a “product of a chorismate metabolic pathway” comprises any of the molecules that are derived from chorismate, such as end products of branches of a chorismate metabolic pathway, downstream metabolites synthesized from end products of branches of a chorismate metabolic pathway, and any intermediate molecule involved in the production of an end product of a branch of the chorismate metabolic pathway.

[0069] Five branches of chorismate metabolism are known. In a first pathway, chorismate mutase converts chorismate to prephenate, which is a precursor of phenylalanine and tyrosine. In a second pathway, anthranilate synthase converts chorismate to anthranilate, which is a precursor of tryptophan. In a third pathway, aminodeoxychorismate synthase (also known as para-aminobenzoic acid (PABA) synthase) converts chorismate to p-aminobenzoate, which is a precursor of folate. In a fourth pathway, isochorismate synthase converts chorismate to isochorismate, which is a precursor of enterobactin. In a fifth pathway, chorismate lyase converts chorismate to -hydroxybcnzoatc, which is a precursor of ubiquinols and / or menaquinol. Non-limiting examples of chorismate metabolites associated with these pathways are described in detail below. In some embodiments, a composition comprises a chorismate metabolite, e.g., a first chorismate pathway metabolite, a second chorismate pathway metabolite, a third chorismate pathway metabolite, a fourth chorismate pathway metabolite, and / or a fifth chorismate pathway metabolite.

[0070] In some embodiments, a chorismate metabolite is within 25 reactions (e.g., downstream metabolic steps, upstream metabolic steps) of chorismate, e.g., within 24 reactions, within 23 reactions, within 22 reactions, within 21 reactions, within 20 reactions, within 19 reactions, within 18 reactions, within 17 reactions, within 16 reactions, within 15 reactions, within 14 reactions, within 13 reactions, within 12 reactions, within 11 reactions, within 10 reactions, within 9 reactions, within 8 reactions, within 7 reactions, within 6 reactions, within 5 reactions, within 4 reactions, within 3 reactions, within 2 reactions, or within 1 reaction. Preferably, a chorismate metabolite is within 22 reactions of chorismate.

[0071] Aromatic Amino Acid Pathways

[0072] In some embodiments, molecules within a chorismate metabolic pathway comprise certain aromatic amino acids (e.g., tryptophan, tyrosine, phenylalanine). In some embodiments, aromatic amino acids present in compositions described herein are L-isomers of the same. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0073] In some embodiments, chonsmate may be converted to tryptophan via a tryptophan biosynthesis pathway. In a first step of the tryptophan biosynthesis pathway, anthranilate synthase may convert chorismate to anthranilate, which is an upstream metabolite (i.e., precursor) of tryptophan. Tryptophan may be further converted to downstream metabolites through at least three major pathways. In some cases, tryptophan may be converted to kynurenine or derivatives thereof through a kynurenine pathway. In some cases, tryptophan may be converted to serotonin or derivatives thereof through a serotonin pathway. In some cases, tryptophan may be converted to an indole through an indole pathway. Indole may then enter various metabolic pathways, generating numerous downstream metabolites, such as, for example, 3 -indolepropionic acid. In some embodiments, a composition comprises a chorismate metabolite, e.g., a tryptophan pathway metabolite. In some embodiments, a composition comprises a tryptophan pathway metabolite, e.g., serotonin, or indole. In some embodiments, a composition comprises a tryptophan pathway metabolite, e.g., 3-indolepropionic acid. In the kynurenine pathway, tryptophan is converted to kynurenine by tryptophan dioxygenase or indoleamine dioxygenase. Kynurenine may then be converted to several molecules, including but not limited to kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, and hydroxyanthranilic acid. Kynurenine as well as its downstream metabolites (including kynurenic acid, xanthurenic acid, quinolinic acid and picolinic acid) are involved in various known biological processes, including neurotransmission, inflammation immune response, and mucosal protective effects in the gut. Other downstream metabolites of kynurenine, including hydroxyanthranilic acid, have neurotoxic effects. In some embodiments, a composition comprises a tryptophan pathway metabolite, e.g., kynurenine and / or one or more of its downstream metabolites.

[0074] In the serotonin pathway, the enzyme tryptophan hydroxylase (TPH) converts tryptophan into 5 -hydroxy tryptophan (5-HTP), which is then converted to serotonin (5-HT) by the enzyme Aromatic Amino Acid Decarboxylase (AAAD). Serotonin, a neurotransmitter, has a wide range of physiological functions in the brain and the periphery through its activation of 5-HT receptors. Serotonin itself can then be converted into several molecules, including melatonin.

[0075] Indoles are the third major category of molecules deriving from tryptophan. In the case of indoles, the microbiota play a main role in producing indoles. For example, in some cases, the bacterium Clostridium sporogenes converts tryptophan into the neurotransmitter tryptamine. In some cases, indoles may trigger signaling from AhR, which can trigger various immune PCT / US25 / 43182 22 August 2025 (22.08.2025) responses. 3-indoleprionic acid, an indole metabolite, is a potent anti-oxidant and may be neuroprotective against oxidotoxins.

[0076] Chorismate may also be converted to tyrosine and / or phenylalanine. In some cases, chorismate mutase may convert chorismate to prephenate, which is a precursor of tyrosine and phenylalanine. Prephenate may be converted to tyrosine and phenylalanine through alternative pathways. For example, prephenate aminotransferase (PPA-AT) produces L-arogenate from prephenate, which can, in turn, be dehydrated or decarboxylated to phenylalanine by arogenate dehydratase (ADT) or instead dehydrogenated / decarboxyled into tyrosine by aroegenate dehydrogenase (ADH). In another example, prephenate can be dehydrated / decarboxylated to form phenylpyruvate and then transaminated to phenylalanine. In yet another example, prephenate can be dehydrogenated / decarboxylated to form 4-hydroxyphenylpyruvate and transaminated into tyrosine. Downstream products of tyrosine and / or phenylalanine include, for example, P-hydroxyphenyllactic acid, tyramine, dopamine, folate, ferulic acid, 4- hydroxyphenylacetic acid, and 3-(3-Hydroxyphenyl)propanoic acid.

[0077] In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises an aromatic amino acid and / or a molecule within the tryptophan biosynthesis pathway or tyrosine and / or phenylalanine biosynthesis pathways. In some embodiments, the aromatic amino acids comprise L-tryptophan, L-tyrosine, L- phenylalanine, or a combination thereof.

[0078] In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises tryptophan and / or a molecule within the tryptophan biosynthesis pathway (e.g., a molecule of a tryptophan metabolite subpathway). In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises a molecule of a tryptophan metabolite subpathway (e.g., a kynurenine and / or a molecule within the kynurenine pathway; serotonin and / or a molecule within the serotonin pathway; indole and / or a molecule within the indole pathway. In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises anthranilate, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, hydroxy anthranilic acid, serotonin, 5 -hydroxy tryptophan (5-HTP), serotonin (5-HT), melatonin, indoles, or a combination thereof. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises 5-hydroxy tryptophan, L-tryptophan, phrenate, L-arogenate, phenylpyruvate, 4-hydroxyphenylpyruvate, L-tyrosine, L-phenylalanine, P-hydroxyphenyllactic PCT / US25 / 43182 22 August 2025 (22.08.2025) acid, ferulic acid, 4-hydroxyphenylacetic acid, and 3-(3-Hydroxyphenyl)propanoic acid, or combinations thereof.

[0079] In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises L-tyrosine and / or L-phenylalanine and / or a molecule within the tyrosine and / or phenylalanine biosynthesis pathway (e.g., a molecule of a tyrosine and / or phenylalanine metabolite subpathway). In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises a molecule of a tyrosine metabolite subpathway (e.g., phrenate and / or a molecule within the phrenate pathway. In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises prephenate, L-arogenate, L-phenylalanine, L-tyrosine, phenylpyruvate, 4- hydroxyphenylpyruvate, P-hydroxyphenyllactic acid, tyramine, dopamine, folate, ferulic acid, 4- hydroxyphenylacetic acid, and 3-(3-Hydroxyphenyl)propanoic acid, or a combination thereof. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises prephenate, L-arogenate, L-phenylalanine, L-tyrosine, phenylpyruvate, 4-hydroxyphenylpyruvate, P- hydroxyphenyllactic acid, tyramine, dopamine, folate, ferulic acid, 4-hydroxyphenylacetic acid, and 3-(3-Hydroxyphenyl)propanoic acid, or combinations thereof.

[0080] Folate Pathway

[0081] In some embodiments, molecules within a chorismate metabolic pathway comprise folinic acid.

[0082] In some cases, the enzyme aminodeoxychorismate synthase (also known as PABA synthase) converts chorismate toward folate biosynthesis. Folate (also known as Vitamin B9) is required for DNA and RNA synthesis as well as for the metabolism of amino acids and nucleic acids, for example, methionine, adenosine, guanine, and lysine, and intermediates (e.g., S- Adenosyl methionine, homocysteine, hypoxanthine, xanthine). The term “folinic acid” refers to a synthetic but identical version of folate and is used interchangeably herein. A lack of folate can lead to neural tube defects and, for this reason, has historically been supplemented within some transgenic foods. A portion of the human gut microbiota possess the genes capable of producing and modifying folate. Folate is also dependent on Vitamin B12 (Cobalamin) for the conversion of N5-methyl tetrahydrofolate into the active form of folate, tetrahydrofolate (THF). Cobalamin also plays an important regulatory role in folate and ubiquinone biosynthesis by acting as a cofactor for an important transcriptional regulator. In some embodiments, a composition (e.g., ., a nutraceutical composition or a pharmaceutical composition) comprises folinic acid and / or a PCT / US25 / 43182 22 August 2025 (22.08.2025) molecule within the folate biosynthesis pathway (e.g., a metabolite of folate). In some embodiments, the molecule within the folate biosynthesis pathway comprises cobalamin, tetrahydrofolate, methionine, adenosine, guanine, lysine, S-adenosyl methionine, homocysteine, hypoxanthine, xanthine, or combinations thereof. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises folinic acid.

[0083] Ubiquinol and. Menaquinol Pathways

[0084] In some embodiments, molecules within a chorismate metabolic pathway comprise ubiquinols and menaquinol.

[0085] In some cases, chorismate may branch toward ubiquinol and menaquinol production when converted to p-hydroxybcnzoatc by chorismate lyase. These molecules are typically found in cellular membranes and are part of electron transport chains. Ubiquinone (also referred to as Coenzyme Q) is utilized for aerobic respiration while menaquinones are commonly used by bacteria for anaerobic respiration and lactic acid fermentation. Menaquinones are also called Vitamin K2 and can vary depending on the length of their isoprenoid carbon chains. Menaquinone-4 (MK4) is the main form of Vitamin K in the brain, and serum concentrations of MK4 may be lower in children with ASD. About 75% of MK4 is produced in the gut and it is reportedly higher in males than females. Given MK4’s roles in neural development, there have been some hypotheses that it may be important to ASD pathophysiology. There are also reports of a correlation between Vitamin K levels and improvement in Autism severity. In some same cases, altered levels of ubiquinol and / or menaquinol production by gut microbiota may have a disproportional effect on male brain development.

[0086] In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises ubiquinol, menaquinol, and / or a molecule within the ubiquinol and / or menaquinol biosynthesis pathway and / or combinations thereof. In some embodiments, the molecule within the ubiquinol and / or menaquinol biosynthesis pathway comprises Vitamin K2.

[0087] Siderophore Pathways

[0088] In some embodiments, molecules within a chorismate metabolic pathway comprise siderophores (e.g., enterobactin).

[0089] In some cases, chorismate may branch toward enterobactin production when converted to isochorismate by an isochorismate hydroxymutase. Enterobactin is a siderophore produced by PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0090] Gram- negative bacteria; enterobactin has a high affinity for ferric iron, an essential component of many metabolic processes in bacteria and other living organisms (e.g., mammals). Low levels of iron are sometimes associated with ASD, such as ASD with GI symptoms.

[0091] In some embodiments, a composition (e.g., a nutraceutical composition or a

[0092] 5 pharmaceutical composition) comprises enterobactin, and / or a molecule within the enterobactin biosynthesis pathway and / or combinations thereof. In some embodiments, the molecule within the enterobactin pathway comprises isochorismate.

[0093] Additional Active Ingredients

[0094] In some embodiments, a composition (e.g., a nutraceutical composition or a

[0095] 10 pharmaceutical composition) comprises a chorismate metabolite and an additional active ingredient. In some embodiments, the additional active ingredient comprises one or more of L- camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, p-hydroxyphenyllactic acid, ferulic acid, 4-hydroxyphenylacetic acid, 3-(3-hydroxyphenyl)propanoic acid, 3- indolepropionic acid, methionine, S-adenosyl methionine, homocysteine, adenosine, guanine,

[0096] 15 hypoxanthine, xanthine, L-Lysine, or combinations thereof.

[0097] Table 2, Additional Active ingredients PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0098] L-Carnosine (i.e., Carnosine) is a dipeptide of P-alanine and L-histidine and a potent antioxidant. L-camosine is typically found in muscle and brain tissue. Dietary L-carnosine can be derived from animal-source foods (e.g., muscle tissue), and can be naturally produced in the

[0099] 5 body from P-alanine and L-histidine; while L-carnosine is not produced in plants, low concentrations of P-alanine and L-histidine can be derived from plant tissue. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and L-Carnosine. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0100] Riboflavin, also known as vitamin B2, is known to play an essential role in health and metabolism. Riboflavin is essential for the formation of FMN and FAD, two major coenzymes involved in numerous metabolic processes (e.g., energy metabolism, cell respiration, metabolism of carbohydrates, protein, and fats). Functional vitamin B2 is also a known essential co-factor in the maintenance of the activity of vitamin B12, and riboflavin deficiencies may be associated with deficiencies in functional vitamin B12. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and riboflavin.

[0101] Vitamin D3, also known as cholecalciferol, is a form of vitamin D which is considered important for bone health, immune function, cellular growth and overall well-being. Vitamin D3 is largely synthesized in an inactive form in the epidermis of the skin after sun exposure, but smaller amounts can also be derived from dietary sources (e.g., flesh of fatty fishes, vitamin D- fortified foods). Activation of vitamin D occurs in the liver and kidneys. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and vitamin D3.

[0102] Choline, formerly known as vitamin B4, is an essential nutrient and plays an important role in brain development, neurotransmitter synthesis (acetylcholine), methyl-group metabolism (homocysteine reduction), cell-membrane signaling (phospholipids), synthesis of methionine, and lipid transport (lipoproteins). Choline is typically derived from dietary sources (e.g., certain plant sources, such as peanuts, beans, nuts, seeds, and animal sources, such as organ meats, egg yolks, dairy), but can be synthesized de novo as well. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and choline.

[0103] Vitamin B6 is a B vitamin and an essential nutrient. Though microbiota in the gut can produce vitamin B6, vitamin B6 cannot be synthesized by human cells, and thus is typically also derived from dietary sources (e.g., several plant foods, some animal sources) or supplementation. Dietary deficiency of B6 is rare. Functionally, vitamin B6 is known to be involved in macronutrient metabolism, neurotransmitter synthesis (e.g., serotonin, GABA), and as a coenzyme in many metabolic functions. Large doses of B6 are sometimes associated with undesirable side effects, which can be mitigated with magnesium supplementation. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and vitamin B6. In some embodiments, a PCT / US25 / 43182 22 August 2025 (22.08.2025) composition (e.g., a nutraceutical composition or a pharmaceutical composition comprising a chorismate metabolite) comprises vitamin B6 and magnesium.

[0104] Magnesium is an essential nutrient responsible for over 300 biochemical reactions in the body, including all in ATP synthesis and synthesis of nucleic acids. Magnesium is typically derived from plant food sources, such as spices, nuts, cocoa, and green leafy vegetables. Supplementation of magnesium is associated with improvements in gastrointestinal issues, mood regulation, energy production, and physical performance. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and magnesium.

[0105] Hydroxycinnamic acids and their derivatives may have several beneficial effects in the mammalian body, including antioxidant activity, antifungal activity, potential anti-cancer activity, anti-inflammatory effects, and protective effects in various tissues and organs. Derivatives of hydroxycinnamic acid include, for example, p-hydroxyphenyllactic acid, ferulic acid, 4-hydroxyphenylacetic acid, and 3-(3-Hydroxyphenyl)propanoic acid. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and a derivative of hydroxycinnamic acid. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and p- hydroxyphenyllactic acid. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and ferulic acid. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and 4- hydroxyphenylacetic acid. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and 3-(3-Hydroxyphenyl)propanoic acid.

[0106] 3-Indolepropionic acid is an antioxidant with potential inhibitory activity on betaamyloid fibril formation. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and 3- Indolepropionic acid.

[0107] Methionine is an essential amino acid and a precursor for other amino acids, such as cysteine and taurine, compounds such as S-adenosyl methionine, homocysteine, and other important components of human metabolic pathways. S-adenosyl methionine (SAM) is a cosubstrate in several anabolic reactions, especially in the liver. Homocysteine is an important PCT / US25 / 43182 22 August 2025 (22.08.2025) intermediate of several metabolites of the methionine and folate cycles. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and methionine. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and S-adenosyl methionine. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and homocysteine.

[0108] Adenosine is a critical precursor of several essential molecules of the body, including nucleotides and energy carriers (e.g., AMP / ADP / ATP). In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and adenosine.

[0109] Guanine is a purine nucleotide base and is critical for nucleic acid function and synthesis. Guanine may be involved in inhibition of glutamate, and thus may be important for cognitive functions. Xanthine is a product of purine degradation and can be derived directly from guanine or from hypoxanthine. Xanthine can act in opposition to adenosine and may have a role in alertness in the CNS. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and Guanine. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and Hypoxanthine. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and Xanthine.

[0110] Lysine is an important component of several proteins and is associated with neurological function. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate metabolite as described herein and L- Lysine.

[0111] In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a chorismate precursor; and an additional active ingredient. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises D-erythrose 4-phosphate, phosphoenolpyruvate, DAHP, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, 5-O-carboxyvinyl-3- phosphoshikimate, or a combination thereof; and an additional active ingredient. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0112] In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises a tryptophan and / or a molecule within the tryptophan biosynthesis pathway (e.g., a kynurenine and / or a molecule within the kynurenine pathway; serotonin and / or a molecule within the serotonin pathway; indole and / or a molecule within the indole pathway); and an additional active ingredient. In some embodiments, a composition (e.g., a nutraceutical composition or pharmaceutical composition) comprises anthranilate, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, hydroxyanthranilic acid, serotonin, 5-hydroxy tryptophan (5-HTP), serotonin (5-HT), melatonin, indoles, or a combination thereof. In some embodiments, a composition (e.g., a pharmaceutical composition) comprises 5-hydroxy tryptophan, L-tryptophan, phrenate, L-arogenate, phenylpyruvate, 4- hydroxyphenylpyruvate, L-tyrosine, L-phenylalanine, or a combination thereof; and an additional active ingredient.

[0113] In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises folinic acid and / or a molecule within the folate biosynthesis pathway; and an additional active ingredient. In some embodiments, the molecule within the folate biosynthesis pathway comprises cobalamin, tetrahydrofolate, methionine, adenosine, guanine, lysine, S-adenosyl methionine, homocysteine, hypoxanthine, xanthine, or combinations thereof; and an additional active ingredient. In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises folinic acid; and an additional active ingredient.

[0114] In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises ubiquinol, menaquinol, and / or a molecule within the ubiquinol and / or menaquinol biosynthesis pathway or combinations thereof; and an additional active ingredient. In some embodiments, the molecule within the ubiquinol and / or menaquinol biosynthesis pathway comprises Vitamin K2; and an additional active ingredient.

[0115] In some embodiments, a composition (e.g., a nutraceutical composition or a pharmaceutical composition) comprises enterobactin, and / or a molecule within the enterobactin biosynthesis pathway or combinations thereof; and an additional active ingredient. In some embodiments, the molecule within the enterobactin pathway comprises isochorismate; and an additional active ingredient. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0116] Beneficial, Prophylactic, and / or Therapeutic Uses

[0117] In some embodiments, provided herein are compositions (e.g., nutraceutical compositions, pharmaceutical compositions) and methods useful for, inter alia, influencing one or more neurological and / or cognitive functions in a subject, for example, in a neurotypical individual, in a subject at risk of developing one or more symptoms of a neurological disorder, or in a subject having one or more signs or symptoms of a neurological disorder. In some embodiments, provided herein are compositions (e.g., nutraceutical compositions, pharmaceutical compositions) and methods useful for, inter alia, preventing (e.g., delays the onset of) or reducing the likelihood of one or more signs or symptoms of a neurological disorder in a subject, for example, in a subject having or being at risk of developing a neurological disorder. In some embodiments, provided herein are compositions (e.g., nutraceutical compositions, pharmaceutical compositions) and methods useful for, inter alia, alleviating (e.g., reducing or eliminating, slowing the progression) or treating one or more signs or symptoms of a neurological disorder in a subject, for example, in a subject having one or more signs or symptoms of a neurological disorder. In some embodiments, compositions (e.g., nutraceutical compositions, pharmaceutical compositions) and methods described herein provide one or more beneficial effects, prophylactic effects, or therapeutic effects to a subject.

[0118] A “beneficial effect” refers to one or more desired biological activities in a neurotypical subject and / or behaviors of the neurotypical subject which are imparted directly or indirectly by an active ingredient (e.g., chorismate metabolite). In some embodiments, the desired biological activity comprises modulating a level of a chorismate metabolite in the subject. In some embodiments, the desired biological activity is a change in level of a chorismate metabolite in the gut of the subject. In some embodiments, the change in level comprises decreasing the level. In some embodiments, the change in level comprises increasing the level. In some embodiments, the desired biological activity comprises influencing one or more neurological and / or cognitive functions in the subject.

[0119] A “prophylactic effect” refers to an effect which prevents (e.g., delays the onset of) or reduces the likelihood of the development of one or more signs or symptoms of a disorder (e.g., neurological disorder) in a subject. While a prophylactic effect may be understood to comprise one or more beneficial effects, a beneficial effect is not necessarily a prophylactic effect.

[0120] A “therapeutic effect” refers to an effect which alleviates (e.g., reduces or eliminates, slows the progression) or treats one or more signs or symptoms of a disorder (e.g., neurological PCT / US25 / 43182 22 August 2025 (22.08.2025) disorder) in a subject. While a therapeutic effect may be understood to comprise one or more beneficial effects, a beneficial effect is not necessarily a therapeutic effect.

[0121] Neurological / Cognitive Effects

[0122] In some embodiments, a composition (e.g., nutraceutical composition, pharmaceutical composition) described herein, when provided (e.g., applied, administered) to a subject, confers a beneficial effect in a subject, the beneficial effect comprising improving or enhancing one or more neurological, cognitive, or behavioral functions, e.g., in a neurotypical subject. In some embodiments, a method described herein confers a beneficial effect in a subject, the beneficial effect comprising improving or enhancing one or more neurological, cognitive, or behavioral functions, e.g., in a neurotypical subject.

[0123] In some embodiments, a composition (e.g., nutraceutical composition, pharmaceutical composition) described herein, when provided (e.g., applied, administered) to a subject, confers a prophylactic effect in a subject, the prophylactic effect comprising preventing (e.g., delaying the onset of) or reducing the likelihood of the development of one or more signs or symptoms of a disorder (e.g., neurological disorder) in a subject, e.g., in a subject at risk of developing a neurological disorder, or in a subject having or suspected of having a neurological disorder. In some embodiments, a method described herein confers a prophylactic effect in a subject, the prophylactic effect comprising preventing (e.g., delaying the onset of) or reducing the likelihood of the development of one or more signs or symptoms of a disorder (e.g., neurological disorder) in a subject, e.g., in a subject at risk of developing a neurological disorder, or in a subject having or suspected of having a neurological disorder.

[0124] In some embodiments, a composition (e.g., nutraceutical composition, pharmaceutical composition) described herein, when provided (e.g., applied, administered) to a subject, confers a therapeutic effect in a subject, the therapeutic effect comprising alleviating (e.g., delaying or reducing the progression of, improving, reducing) or eliminating one or more signs or symptoms of a disorder (e.g., neurological disorder) in a subject, e.g., in a subject having or suspected of having a neurological disorder. In some embodiments, a method described herein confers a therapeutic effect in a subject, the therapeutic effect comprising alleviating (e.g., delaying or reducing the progression of, improving, reducing) or eliminating one or more signs or symptoms of a disorder (e.g., neurological disorder) in a subject, e.g., in a subject having or suspected of having a neurological disorder. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0125] In some embodiments, a beneficial, prophylactic, and / or therapeutic effect comprises a neuroprotective effect. As used herein, the term “neuroprotection” refers to biological effects related to the preservation of CNS tissues and cells (e.g., CNS structure, function, and / or integrity). In some embodiments, a neuroprotective effect comprises a reduction of the severity of a neurological disorder or a symptom thereof. In some embodiments, a neuroprotective effect comprises a reduction of the incidence (e.g., frequency) of a neurological disorder or a symptom thereof. In some embodiments, a neuroprotective effect comprises a reduction of the progression of a neurological disorder or a symptom thereof. In some embodiments, a neuroprotective effect comprises a prevention of a neurological disorder or a symptom thereof. In some embodiments, a neuroprotective effect comprises a reduction of cell death in the CNS (e.g., a reduction in the death of dopaminergic cells), for example, a reduction of cell death associated with normal aging or a reduction of cell death associated with a neurodegenerative disorder. In some embodiments, a neuroprotective effect comprises a reduction of neuroinflammation (e.g., oxidative stress), for example, a reduction of neuroinflammation as a result of a non-neurological disease or disorder (e.g., a viral infection). In some embodiments, a neuroprotective effect comprises a reduction in the accumulation of metabolic waste (e.g., P-amyloid, r-plaques) in the CNS.

[0126] In some embodiments, a beneficial, prophylactic, and / or therapeutic effect comprises a neuroregenerative effect. As used herein, the term “neuroregeneration” refers to biological activity related to the regrowth or repair of CNS tissues and cells (e.g., CNS structure, function, and / or integrity). In some embodiments, a neuroregenerative effect promotes healing of a neuronal injury (e.g., an injury resulting from a brain injury, for example, as the result of a cerebrovascular accident (e.g., ischemic stroke, hemorrhagic stroke), brain tumor, or traumatic brain injury. In some embodiments, a neuroregenerative effect promotes healing of a neuronal injury associated with or believed to be caused by reduced blood flow to the brain (e.g., myocardial ischemia). In some embodiments, a neuroregenerative effect restores impaired serotonin signaling to normal or near normal levels. In some embodiments, a neuroregenerative effect promotes one or more neurotrophic functions, for example, growth, survival, differentiation, maturity, and / or connectivity of CNS neurons.

[0127] In some embodiments, a beneficial, prophylactic, and / or therapeutic effect comprises an enhancement or improvement of one or more cognitive functions. The term “cognitive function,” as used herein, refers to a mental ability, such as mental stability, memory / recall, problem solving, reasoning, decision-making, learning, language (e.g., linguistic ability), perception, and attention. A cognitive function can be understood to be enhanced by application PCT / US25 / 43182 22 August 2025 (22.08.2025) of the composition to a subject using any test or assessment known in the art. Improvements to cognitive function may be determined, for example, by comparing results of an assessment of the cognitive function after application of the composition to the subject to results of the same assessment prior to application of the composition to the subject. In some embodiments, a beneficial effect comprises an enhancement or improvement of one or more normal cognitive functions in a neurotypical subject. In some embodiments, a prophylactic and / or therapeutic effect comprises an enhancement or improvement of one or more impaired cognitive functions in a subject having or suspected of having a neurological disorder.

[0128] In some embodiments, a beneficial, prophylactic, and / or therapeutic effect comprises enhancement or improvement of or more behavioral functions. The term “behavior" refers to anything that a subject does in response to a given stimulation (e.g., stimulus, context, set of conditions), such as sleep / wake behavior, social behavior (e.g., social interactions), speaking behavior (e.g., conversation, speech), motor performance (e.g., fine motor behavior, gross motor behavior). Behavioral functions may be used to determine a cognitive function. In some embodiments, a beneficial effect comprises an enhancement or improvement of one or more normal behavioral functions in a neurotypical subject. In some embodiments, a prophylactic and / or therapeutic effect comprises an enhancement or improvement of one or more impaired behavioral functions in a subject at risk of developing a neurological disorder.

[0129] Neurological Disorders

[0130] As used herein, the term “neurological disorders” refers to diseases and disorders of the CNS (e.g., a disease or disorder of the brain or spinal cord). In some embodiments, a composition (e.g., a prophylactic composition) described herein, when provided (e.g., applied, administered) to a subject, prevents (e.g., delays the onset of) or reduces the likelihood of the development of one or more signs or symptoms of a neurological disorder. In some embodiments, a composition (e.g., a therapeutic composition), when administered to a subject, alleviates (e.g., delays or reduces the progression and / or severity of) one or more signs or symptoms of a disorder (e.g., neurological disorder) in a subject.

[0131] In some embodiments, a sign of a neurological disorder comprises one or more neuropathophysiological feature associated with the neurological disorder. The term “neuropathophysiological feature” refers to one or more biological (e.g., cellular, structural, metabolic) findings in a subject (e.g., in a sample of a subject) characteristic of a neurological disorder. Neuropathophysiological features in a subject may be determined using a number of PCT / US25 / 43182 22 August 2025 (22.08.2025) known methods in the art, for example, brain imaging (e.g., magnetic resonance imaging (MRI), functional MRI, positron emission topography (PET), magnetoencephalography (MEG), computed tomography (CT) scanning, diffusion tensor imaging (DTI)) and analysis of CNS tissue samples (e.g., cerebrospinal fluid analysis, histology)). In some embodiments, the neuropathophysiological feature comprises degeneration or death of specific brain cell types (e.g., dopaminergic neurons) or brain structures (e.g., neocortex). In some embodiments, the neuropathophysiological feature comprises one or more features of an inflammatory response (e.g., oxidative stress, microglial accumulation). In some embodiments, the neuropathophysiological feature comprises accumulation of one or more metabolic waste products (e.g., P-amyloid, r-plaques). In some embodiments, the neuropathophysiological feature comprise neuronal injury, for example as a result from a brain injury (e.g., traumatic brain injury), a cerebrovascular accident (e.g., ischemic stroke, hemorrhagic stroke, myocardial ischemia). In some embodiments, the neuropathophysiological feature comprises one or more CNS tumors (e.g., glioma, neurofibromas, hemangioblastomas). In some embodiments, the neuropathophysiological feature comprises one or more abnormal gross structural features, for example, head circumference, intracranial volume, ventricular volume, cerebellar volume, interhemispheric connectivity, or intrahemispheric connectivity. In some embodiments, the neuropathophysiological feature comprises one or more abnormalities in synaptic structure and function, for example, balance of excitatory and inhibitory transmission, synaptogenesis, or synaptic homeostasis. In some embodiments, the neuropathophysiological feature comprises one or more abnormalities in neurotransmission, for example, serotonin signaling, glutamate signaling, dopamine signaling, and / or tendency for seizures (e.g., risk of epilepsy).

[0132] In some embodiments, a sign of a neurological disorder comprises one or more cognitive and / or behavioral features associated with the neurological disorder. In some embodiments, a symptom of a neurological disorder comprises one or more dysfunctional cognitive and / or behaviors. In some embodiments, a sign or symptom of a neurological disorder comprises one or more impaired cognitive abilities, such as abnormal affect (e.g., flat affect), abnormal mental stability, impaired memory (e.g., impaired spatial, working, episodic, semantic, prospective, or procedural memory), impaired problem solving, impaired reasoning, impaired decision-making, impaired self-control (e.g., risk taking behaviors, impulse control issues, aggression, criminal behaviors), impaired learning ability (e.g., dyslexia, dyscalculia, dysgraphia, intellectual disability), impaired language abilities (e.g., perception of language, language processing, ability to read or write, abnormal speech (e.g., aphasia, dysphasia, difficulty following or joining PCT / US25 / 43182 22 August 2025 (22.08.2025) conversation, stuttering), altered perception (e.g., loss or reduction or one or more sensory abilities), and / or impaired attention (e.g., inattention, hyperfixation, impaired cognitive switching).

[0133] In some embodiments, a sign or symptom of a neurological disorder comprises one or more dysfunctional behaviors, such as abnormal sleep / wake behavior (e.g., narcolepsy, insomnia, abnormal circadian rhythm), abnormal social behavior (e.g., social avoidance, unstable relationships, impaired communication), abnormal speaking behavior (e.g., aphasia, dysphasia, difficulty following or joining conversation, abnormal speech), impaired motor behavior (e.g., dyskinesia, chorea, dystonia, tremors, spasms, impaired fine motor behavior), seizures or epilepsy, or a combination thereof.

[0134] Neurodevelopmental Disorders

[0135] In some embodiments, the neurological disorder is a neurodevelopmental disorder. As used herein, the term “neurodevelopmental disorder” refers to disorders in which the normal development of the nervous system and / or one or more cognitive abilities is impaired. In some embodiments, a subject has or is suspected of having a neurodevelopmental disorder. In some embodiments, a sign or symptom of a neurodevelopmental disorder comprises one or more of abnormalities in affect, learning ability, self-control, memory, attention, speech, behavior, or a combination thereof. In some embodiments, a sign or symptom of a neurodevelopmental disorder comprises seizures or a seizure disorder (e.g., epilepsy).

[0136] In some embodiments, the neurodevelopmental disorder is an autism spectrum disorder (ASD; e.g., classic autism, Asperger’s syndrome), an attention deficit disorder, Fragile X syndrome, Rett syndrome, pervasive developmental disorder not otherwise specified (PDD- N08), childhood disintegrative disorder (CDD), tuberous sclerosis, Fragile X syndrome, Rett syndrome, Angelman syndrome, Dupl5q syndrome, 22ql3.3 Deletion syndrome, Prader-Willi syndrome, velocardiofacial syndrome, Smith-Lemli-Opitz syndrome, or any combination thereof. In certain embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject having or at risk of having a neurodevelopmental disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurodevelopmental disorder).

[0137] In preferred embodiments, a neurological disorder is ASD and / or a comorbidity of ASD. Examples of comorbidities of ASD include, but are not limited to, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), PCT / US25 / 43182 22 August 2025 (22.08.2025) epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder. Signs and symptoms of ASD include, but are not limited to, irritability, sleeplessness, speech and communication issues, aggression, food selectivity, sensory sensitivity (e.g., textural aversion), digestive issues, socialization issues, limited repetitive patterns of behavior and interests, anxiety attacks, self-aggression, and mood disorders. In certain embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject exhibiting one or more signs or symptoms of a neurodevelopmental disorder.

[0138] In some embodiments, a subject having or suspected of having ASD (e.g., exhibiting one or more signs or symptoms of ASD) has or is suspected of having a chorismate subtype of ASD. In some embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject having or suspected of having ASD (e.g., exhibiting one or more signs or symptoms of ASD) or suspected of having a chorismate subtype of ASD. A “chorismate subtype of ASD” refers to a subtype of ASD which is characterized by an altered level of chorismate and / or a molecule within a chorismate metabolic pathway (e.g., the chorismate superpathway) in a sample from the subject, relative to one or more neurotypical individuals. In some cases, the altered level of chorismate and / or the molecule within the chorismate metabolic pathway may be above or below a certain threshold.

[0139] Glyphosate Subtypes of ASD

[0140] Certain chemical compounds that target one or more enzymes of the shikimate pathway may be linked to ASD, for example, glyphosate. Glyphosate targets the enzyme EPSPS (as shown in FIG. 1), preventing the production of 5-O-(Carboxyvinyl)-3-phosphoshikimate (which may be converted into chorismate by chorismate synthase). Indeed, one study finds that an increase in the number of children with autism corresponds to an increase in the amount of glyphosate applied to corn and soy. See: Shaw, Elevated urinary glyphosate and clostridia metabolites with altered dopamine metabolism in triplets with autistic spectrum disorder or suspected seizure disorder: A case study, Integr Med (Encinitas), 16(1): 50-57 (2017).

[0141] Without wishing to be bound by theory, ingestion of or exposure to glyphosate (e.g., trace amounts in com or soy) is thought to kill beneficial bacteria in the gut microbiome of a subject. When beneficial bacteria, but not potentially pathological bacteria (e.g., Clostridia), are absent in the gut microbiome, these potentially pathological bacteria can produce molecules which are harmful to the subject (e.g., toxins), for example, by interfering with one or more enzymes associated with chorismate metabolism (e.g., Class I EPSPS enzymes). Accordingly, in PCT / US25 / 43182 22 August 2025 (22.08.2025) some embodiments, exposure of a subject to glyphosate may result in a decreased level of chorismate (e.g., in a gastrointestinal tract of the subject). In some embodiments, exposure of a subject to glyphosate may result in the subject exhibiting one or more signs or symptoms of ASD and / or having a higher risk of developing ASD. In some cases, exposure of a subject to glyphosate may contribute to the development of other neurological disorder, or signs or symptoms thereof, non-limiting examples of which include: impaired serotonin signaling, anorexia nervosa, Alzheimer’s disease, Parkinson’s disease, and ADHD. In some embodiments, exposure of a subject to glyphosate comprises ingestion of glyphosate. In some embodiments, exposure of a subject to glyphosate comprises exposure to glyphosate in utero (e.g., via ingestion of glyphosate by the subject’s mother during pregnancy).

[0142] In certain embodiments, a method comprises determining that a subject has or is at risk of having a subtype of ASD (e.g., a chorismate subtype of ASD) based on an elevated level of glyphosate in the subject (e.g., relative to one or more neurotypical individuals). In some embodiments, determining that a subject has or is at risk of having a subtype of ASD (e.g., a chorismate subtype of ASD) comprises determining that the subject has a deficiency in one or more chorismate metabolites. In some embodiments, the one or more chorismate metabolites comprise tetrahydrofolate, shikimate, L-tyrosine, L-tryptophan, tyramine, dopamine, 3- indolepropionic acid, p-hydroxyphenyllactic acid, and / / YUM- ferulic acid. In some embodiments, determining that a subject has or is at risk of having a subtype of ASD (e.g., a chorismate subtype of ASD) comprises determining that the subject has a deficiency in one or more other metabolites, such as riboflavin, hypoxanthine, or xanthurenic acid. In certain embodiments, a method comprises applying (e.g., administering) a composition described herein is administered to a subject determined to have an elevated level of glyphosate (e.g., relative to one or more neurotypical individuals).

[0143] Neuropsychiatric Disorders

[0144] In some embodiments, the neurological disorder is a neuropsychiatric disorder. As used herein, the term “neuropsychiatric disorder” refers to disorders in which one or more of cognitive, affective, behavioral, or learning and memory functions are dysfunctional. In some embodiments, a subject has or is suspected of having a neuropsychiatric disorder. In some embodiments, a subject exhibits one or more signs or symptoms of a neuropsychiatric disorder. In some embodiments, the neuropsychiatric disorder is a disorder recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM) (e.g., DSM-IV, DSM-5). In some PCT / US25 / 43182 22 August 2025 (22.08.2025) embodiments, the neuropsychiatric disorder is anxiety disorder, attention deficit disorder, bipolar disorder, cognitive disorder, delirium, dementia, depression, dissociative disorders, eating disorders (e.g., anorexia nervosa), impulse-control disorders, mood disorders, mania, obsessive-compulsive disorders, personality disorders (e.g., borderline personality disorder), psychosis, psychotic disorders (e.g., schizophrenic disorders), post-traumatic stress disorders, sexual disorders, sleep disorders, somatoform disorders, substance abuse disorders (e.g., alcoholism, drug addiction), or any combination thereof. In certain embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject having or at risk of having a neuropsychiatric disorder (e.g., a subject exhibiting one or more signs or symptoms of a neuropsychiatric disorder). In certain embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject exhibiting one or more signs or symptoms of a neuropsychiatric disorder.

[0145] Neurodegenerative Diseases

[0146] In some embodiments, the neurological disorder is a neurodegenerative disease. As used herein, the term “neurodegenerative disease” refers to any disease or disorder characterized by progressive loss of neuronal cells, reduction in neuronal function and structure, and / or neuronal death in the CNS. In some embodiments, a subject has or is suspected of having a neurodegenerative disease. In some embodiments, a subject exhibits one or more signs or symptoms associated with a neurodegenerative disease. In some embodiments, the signs or symptoms associated with neurodegenerative disease are one or more of cognitive impairment (e.g., mild cognitive impairment, severe cognitive impairment, memory loss, short-term memory loss), ataxia, dementia, disinhibition, hypokinesia, hyperkinesia, or a combination thereof. In some embodiments, the neurodegenerative disease is associated with or believed to be caused by pathological aging. In some embodiments, the neurodegenerative disorder is associated with or believed to be caused by a brain injury, for example, as the result of a cerebrovascular accident (e.g., ischemic stroke, hemorrhagic stroke), brain tumor, or traumatic brain injury. In some embodiments, the neurodegenerative disorder is associated with or believed to be caused by reduced blood flow to the brain (e.g., myocardial ischemia).

[0147] In some embodiments, the neurodegenerative disease is Alzheimer's disease (AD), preclinical Alzheimer's disease (PCAD), Parkinson's disease (PD), Huntington's disease (HD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS, e.g., familial ALS and sporadic ALS), multiple sclerosis (MS), vascular dementia (cerebral amyloid angiopathy and PCT / US25 / 43182 22 August 2025 (22.08.2025) stroke), dementia with Lewy bodies, HIV dementia, age- associated memory impairment (AAMI), age-related cognitive decline (ARCD), Batten disease, Creutzfeldt-Jakob disease, cognitive impairment no dementia (CIND), or any combination thereof.

[0148] In certain embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject having or at risk of having a neurodegenerative disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurodegenerative disorder). In certain embodiments, a method comprises applying (e.g., administering) a composition described herein to a subject exhibiting one or more signs or symptoms of a neurodegenerative disorder.

[0149] Compositions

[0150] In some aspects, provided in the present disclosure are compositions (e.g., nutraceutical compositions, pharmaceutical compositions) comprising a chorismate metabolite as described herein. In some aspects, provided in the present disclosure are compositions (e.g., nutraceutical compositions, pharmaceutical compositions) comprising a chorismate metabolite and an additional active ingredient. In some aspects, a composition (e.g., nutraceutical composition, pharmaceutical composition) further comprises a metabolite of the shikimate pathway. In some aspects, compositions (e.g., nutraceutical compositions, pharmaceutical compositions) are delivered to a subject in a form that targets the gut (e.g., gastrointestinal tract) of the subject. In some aspects, compositions (e.g., nutraceutical compositions, pharmaceutical compositions) targeting the gut of the subject are configured for release by a microbial organism.

[0151] In some embodiments, the compositions are pharmaceutical compositions or nutraceutical compositions. “Pharmaceutical compositions" and “nutraceutical compositions,” as used herein, refer to formulations of a chorismate metabolite, and optionally an additional active ingredient, in a medium generally accepted in the art for the delivery of the chorismate metabolite, and optional additional active ingredient, to mammals (e.g., humans). It will be understood that a pharmaceutical composition is a medicament, e.g., a therapeutic and / or prophylactic substance. A pharmaceutical composition (e.g., therapeutic composition, prophylactic composition) may be formulated as, for example, a prescription drug, an over the counter (OTC) medication, a botanical drug, an herbal medicine, a homeopathic agent, a functional food, a pharmaceutical suspension, a sprinkle formula (e.g., a powder for dissolution in a beverage and / or mixture with soft food), or any other type of health care product reviewed and approved by a government agency. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0152] In some embodiments, the compositions are nutraceutical compositions. It will be understood that a nutraceutical composition is a dietary supplement (e.g., vitamin pills), or a food or food product, which may have a beneficial effect. A nutritional supplement may be formulated as, for example, a vitamin pill, a nutritional or bioactive component in food, a novel food, a functional food, a fortified food, a beverage, or powder for dissolution in a beverage and / or mixture with soft food, a sprinkle formula, a bar, a food flavor, a food additive, a medical food, or an herbal product.

[0153] Exemplary formulations of pharmaceutical and / or nutraceutical compositions are provided in the section entitled “Formulations.”

[0154] In some embodiments, a pharmaceutical or nutraceutical composition comprises at least one chorismate metabolite, and optionally, an additional active ingredient. In some embodiments, the pharmaceutical or nutraceutical composition comprises a predetermined amount of the one or more chorismate metabolites or a pharmaceutically or nutraceutically acceptable salt thereof. In some embodiments, the pharmaceutical or nutraceutical composition further comprises a predetermine amount of the additional active ingredient or a pharmaceutically or nutraceutically acceptable salt thereof.

[0155] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the chorismate superpathway. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the shikimate pathway. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within an aromatic amino acid biosynthesis pathway. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the tryptophan biosynthesis pathway. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the folate biosynthesis pathway. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the ubiquinol and / or menaquinol biosynthesis pathway. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the siderophore biosynthesis pathway.

[0156] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the chorismate superpathway as described herein; and an additional active ingredient. In some embodiments, a composition (e.g., PCT / US25 / 43182 22 August 2025 (22.08.2025) a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the shikimate pathway as described herein; and an additional active ingredient. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within an aromatic amino acid biosynthesis pathway; and an additional active ingredient. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the tryptophan biosynthesis pathway (e.g., a molecule of a tryptophan metabolite subpathway); and an additional active ingredient. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the folate biosynthesis pathway; and an additional active ingredient. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the ubiquinol and / or menaquinol biosynthesis pathway; and an additional active ingredient. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a molecule within the siderophore biosynthesis pathway; and an additional active ingredient.

[0157] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a chorismate precursor. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises chorismate (e.g., chorismic acid). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises an aromatic amino acid. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises L-tryptophan. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises folinic acid. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises ubiquinol and / or menaquinol. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a siderophore.

[0158] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate superpathway metabolites. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of a chorismate precursor, a molecule within the shikimate pathway, chorismate (e.g., chorismic acid), a molecule within the chorismate superpathway, an aromatic amino acid, a molecule within an aromatic amino acid pathway, L-tryptophan, a molecule within the tryptophan biosynthesis pathway (e.g., a molecule of a tryptophan metabolite subpathway), folinic acid, a molecule within the folate biosynthesis pathway, PCT / US25 / 43182 22 August 2025 (22.08.2025) ubiquinol, menaquinol, a molecule within the ubiquinol and / or menaquinol biosynthesis pathway or combinations thereof; and an additional active ingredient.

[0159] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of a chorismate precursor, a molecule within the shikimate pathway, an aromatic amino acid, a molecule within an aromatic amino acid pathway, L-tryptophan, a molecule within the tryptophan biosynthesis pathway (e.g., a molecule of a tryptophan metabolite subpathway), folinic acid, a molecule within the folate biosynthesis pathway, ubiquinol, menaquinol, a molecule within the ubiquinol and / or menaquinol biosynthesis pathway; and one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or combinations thereof.

[0160] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises a chorismate precursor or a molecule within the shikimate pathway; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises one or more of D-erythrose 4-phosphate, phosphoenolpyruvate, 3- deoxy-D-arabino-heptulosonate-7-phosphate, 3-dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-(carboxyvinyl)-3-phosphoshikimate; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises two or more, three or more, four or more, five or more, six or more, or seven or more of D-erythrose 4- phosphate, phosphoenolpyruvate, 3-deoxy-D-arabino-heptulosonate-7-phosphate, 3- dehydroquinate, 3-dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-0- (carboxyvinyl)-3-phosphoshikimate; and an additional active ingredient (e.g., one or more of L- camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises D-erythrose 4-phosphate, phosphoenolpyruvate, 3-deoxy-D-arabino-heptulosonate-7-phosphate, 3-dehydroquinate, 3- dehydroshikimate, shikimate, shikimate 3-phosphate, and 5-O-(carboxyvinyl)-3- phospho shikimate; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0161] In some embodiments, the composition comprises D-erythrose 4-phosphate; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises phosphoenolpyruvate ; and an additional active ingredient (e.g., one or more of L- PCT / US25 / 43182 22 August 2025 (22.08.2025) camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises 3-deoxy-D-arabino-heptulosonate-7- phosphate; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises 3-dehydroquinate; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises 3-dehydroshikimate; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises shikimate; and an additional active ingredient (e.g., one or more of L- camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises shikimate 3-phosphate; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, the composition comprises 5-0- (carboxyvinyl)-3-phosphoshikimate; and an additional active ingredient (e.g., one or more of L- camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0162] In some embodiments, a composition (e.g., a pharmaceutical composition) comprises one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L-phenylalanine); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L-phenylalanine); and one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of L-tryptophan, L-tyrosine, L-phenylalanine, or a combination thereof; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two or more aromatic amino acids (e.g., L-tryptophan and L-tyrosine, L-tryptophan and L- phenylalanine, L-tyrosine and L-phenylalanine); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, PCT / US25 / 43182 22 August 2025 (22.08.2025) a nutraceutical composition) comprises L-tryptophan, L-tyrosine, and L-phenylalamne; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0163] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises L-tryptophan; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises L-tyrosine; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises L-phenylalanine; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0164] In some embodiments, a composition (e.g., a pharmaceutical composition) comprises L- tryptophan and / or a molecule within the tryptophan biosynthesis pathway (e.g., a molecule of a tryptophan metabolite subpathway); and an additional active ingredient (e.g., one or more of L- camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises L-tryptophan and / or a molecule within the tryptophan biosynthesis pathway (e.g., a molecule of a tryptophan metabolite subpathway); and one or more of L- camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of L-tryptophan, anthranilate, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, hydroxy anthranilic acid, serotonin, 5- hydroxytryptophan (5-HTP), serotonin (5-HT), melatonin, indoles; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or eleven or more of L-tryptophan, anthranilate, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, hydroxy anthranilic acid, 5 -hydroxy tryptophan (5-HTP), serotonin (5-HT), melatonin, indoles; and an additional active ingredient (e.g., one or more of L-camosine, PCT / US25 / 43182 22 August 2025 (22.08.2025) riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof)- In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises anthranilate, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, hydroxyanthranilic acid, serotonin, 5 -hydroxy tryptophan (5-HTP), serotonin (5-HT), melatonin, indoles; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0165] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises L-tryptophan; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises anthranilate; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises kynurenine; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises kynurenic acid; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises xanthurenic acid; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises quinolinic acid; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises picolinic acid; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises hydroxyanthranilic acid; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises serotonin; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0166] Vitamin B6, magnesium, or a combination thereof)- In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises 5 -hydroxy tryptophan (5- HTP); and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises serotonin (5-HT); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises melatonin; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises an indole; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0167] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises folinic acid and / or a molecule within the folate biosynthesis pathway; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of folinic acid, cobalamin, tetrahydrofolate, methionine, adenosine, guanine, lysine, S-adenosyl methionine, homocysteine, hypoxanthine, xanthine; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two or more of folinic acid, cobalamin, tetrahydrofolate, methionine, adenosine, guanine, lysine, S-adenosyl methionine, homocysteine, hypoxanthine, xanthine; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises folinic acid, cobalamin, tetrahydrofolate, methionine, adenosine, guanine, lysine, S-adenosyl methionine, homocysteine, hypoxanthine, xanthine or combinations thereof; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0168] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises folinic acid; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises cobalamin; and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises tetrahydrofolate, methionine, adenosine, guanine, lysine, S-adenosyl methionine, homocysteine, hypoxanthine, xanthine or combinations thereof; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0169] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises ubiquinol, menaquinol, and / or a molecule within the ubiquinol and / or menaquinol biosynthesis pathway or combinations thereof; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises Vitamin K2; and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof).

[0170] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of Vitamin K2, L-tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two or more of Vitamin K2, L-tryptophan, 5 -Hydroxy tryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises three or more of Vitamin K2, L-tryptophan, 5-Hydroxy tryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises four or more of Vitamin K2, L-tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) PCT / US25 / 43182 22 August 2025 (22.08.2025) compnses five or more of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP).

[0171] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more of Vitamin K2, L-tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two or more of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP); and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises three or more of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L- phenylalanine, and folinic acid (5-MFHP); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises four or more of Vitamin K2, L-tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises five or more of Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP); and an additional active ingredient (e.g., one or more of L-camosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP); and an additional active ingredient (e.g., one or more of L-carnosine, riboflavin, Vitamin D3, choline, Vitamin B6, magnesium, or a combination thereof). PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0172] Effective Amounts

[0173] In some embodiments, the predetermined amount is an effective amount. In certain embodiments, the effective amount is an amount sufficient to induce a beneficial effect (e.g., a beneficially effective amount). In certain embodiments, the effective amount is an amount sufficient to induce a therapeutic effect (e.g., a therapeutically effective amount). In certain embodiments, the effective amount is an amount sufficient to induce a prophylactic effect (e.g., a prophylactically effective amount). In certain embodiments, an effective amount (e.g., a therapeutic amount) is an amount sufficient to alleviate (e.g., delay or reduce the onset, progression, and / or severity of) one or more signs or symptoms of a neurological disorder (e.g., ASD) in a subject. In certain embodiments, an effective amount is an amount sufficient to reduce the risk of a subject developing a neurological disorder (e.g., ASD).

[0174] In some embodiments, a predetermined amount of the one or more chorismate metabolites comprises an amount of the chorismate metabolite which is the recommended dietary allowance (RD A) corresponding to the one or more chorismate metabolite. As used herein, the term recommended dietary allowance (RD A) refers to an average daily level of intake sufficient to meet the nutrient requirements of most (97-98%) healthy individuals, for example, as determined by the Food and Nutrition Board of the National Academies of Science, Engineering, and Medicine (e.g., see: ods.od.nih.gov / HealthInformation / nutrientrecommendations.aspx). An RDA for an individual may be calculated differently based on a number of characteristics, for example, sex, age, weight, or pregnancy status.

[0175] In some embodiments, a predetermined amount of the one or more chorismate metabolites comprises an amount of the one or more chorismate metabolite which is less than the RDA corresponding to the one or more chorismate metabolite. In some embodiments, a predetermined amount of the one or more chorismate metabolites comprises an amount of the one or more chorismate metabolite which is no more than 99.9%, no more than 99%, no more than 98%, no more than 97%, no more than 96%, no more than 95%, no more than 94%, no more than 93%, no more than 92%, no more than 91%, no more than 90%, no more than 80%, no more than 70%, no more than 60%, no more than 50%, no more than 40%, no more than 30%, no more than 20%, no more than 10%, or no more than 5% of the RDA corresponding to the one or more chorismate metabolite.

[0176] In some embodiments, a predetermined amount of the one or more chorismate metabolites comprises an amount of the one or more chorismate metabolite which is an amount PCT / US25 / 43182 22 August 2025 (22.08.2025) greater than the RDA corresponding to the one or more chonsmate metabolite. For example, a subject may derive a beneficial effect when provided a composition comprising a predetermined amount of one or more chorismate metabolites, wherein the predetermined amount of the one or more chorismate metabolites exceeds the RDA corresponding to the one or more chorismate metabolites (e.g., if the subject has a decreased level of the one or more chorismate metabolite in the gut of the subject). In some embodiments, a predetermined amount of the one or more chorismate metabolites comprises an amount of the one or more chorismate metabolite which is at least 100%, at least 101%, at least 102%, at least 103%, at least 104%, at least 105%, at least 106%, at least 107%, at least 108%, at least 109%, at least 110%, at least 120%, at least 130%, at least 140%, at least 150%, at least 160%, at least 170%, at least 180%, at least 190%, at least 200%, at least 250%, at least 300%, at least 350%, at least 400%, at least 450%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1000%, at least 1500%, at least 2000%, at least 3000%, at least 4000%, or at least 5000% of the RDA corresponding to the one or more chorismate metabolite.

[0177] In some embodiments, the predetermined amount of the one or more chorismate metabolites is in a range from about 1 mg to 2000 mg (e.g., 1 mg to 10 mg, 1 mg to 50 mg, 1 mg to 100 mg, 10 mg to 50 mg, 10 mg to 100 mg, 50 mg to 100 mg, 100 mg to 150 mg, 100 mg to 200 mg, 150 mg to 200 mg, 200 mg to 250 mg, 250 mg to 300 mg, 300 mg to 400 mg, 400 mg to 500 mg, 500 mg to 750 mg, 750 mg to 1000 mg, 1000 mg to 1250 mg, 1250 mg to 1500 mg, 1500 mg to 2000 mg). In some embodiments, the predetermined amount of the one or more chorismate metabolites is in a range from about 5 pg to 2000 pg (e.g., 1 pg to 10 pg, 1 pg to 50 pg, 1 pg to 100 pg, 10 pg to 50 pg, 10 pg to 100 pg, 50 pg to 100 pg, 100 pg to 150 pg, 100 pg to 200 pg, 150 pg to 200 pg, 200 pg to 250 pg, 250 pg to 300 pg, 300 pg to 400 pg, 400 pg to 500 pg, 500 pg to 750 pg, 750 pg to 1000 pg, 1000 pg to 1250 pg, 1250 pg to 1500 pg, 1500 pg to 2000 pg).

[0178] In some embodiments, two or more chorismate metabolites in a composition (e.g., a pharmaceutical composition, a nutraceutical composition) are present in a predetermined ratio. In some embodiments, the ratio is a molar ratio.

[0179] In some embodiments, each chorismate metabolite is present in the composition (e.g., the pharmaceutical composition, the nutraceutical composition) in a ratio of about 1:1, about 1:1:1, about 1: 1: 1: 1, about 1: 1:1: 1: 1, about 1: 1: 1: 1: 1: 1, about 1: 1: 1: 1: 1: 1: 1, about 1: 1: 1: 1: 1: 1: 1: 1, 1:1:1:1:1:1:1:1:1, about 1:1:1:1:1:1:1:1:1:1, about 1:1:1:1:1:1:1:1:1:1:1, or about l:l:l:l:l:l:l:l:l:l:l:l. In some embodiments, the exact ratio may differ; for example, in some PCT / US25 / 43182 22 August 2025 (22.08.2025) embodiments the ratio is modified (e.g., by a qualified healthcare professional) to improve one or more effects. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises an equimolar mixture of two or more chorismate metabolites.

[0180] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two or more aromatic amino acids (e.g., any two of L- tryptophan, L-tyrosine, and L-phenylalanine) in a predetermined ratio. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises two aromatic amino acids in a ratio from about 1:10 to about 10:1. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises three aromatic amino acids (e.g., L-tryptophan, L-tyrosine, L-phenylalanine) in a ratio from about 1:1:10 to about 10:1:1. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises three aromatic amino acids (e.g., L- tryptophan, L-tyrosine, L-phenylalanine) in a ratio wherein the aromatic amino acid at the highest concentration relative to the aromatic amino acid at the lowest concentration is about 10:1 to about 1:1 (e.g., about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1 or about 1:1). In some embodiments, a composition comprises L- tryptophan, L-tyrosine, and L-phenylalanine in a ratio from about 1:1:10 to about 10:1:1. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises an equimolar mixture of L-tryptophan, L-tyrosine, and L-phenylalanine (i.e., a 1:1:1 mixture of L-tryptophan, L-tyrosine, L-phenylalanine).

[0181] Dose ranges as described herein provide guidance for the application (e.g., administration) of provided compositions (e.g., pharmaceutical compositions, nutraceutical compositions) to an adult. The amount to be applied to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that applied to an adult.

[0182] Pharmaceutical or nutraceutical compositions can be prepared, packaged, and / or sold in bulk, as a single unit dose, and / or as a plurality of single unit doses. A “unit dose” is a discrete amount of the pharmaceutical or nutraceutical composition comprising a predetermined amount of the one or more chorismate metabolites, and optionally an additional active ingredient. The amount of the one or more chorismate metabolites, and, optionally an additional active ingredient is generally equal to the dosage of the active ingredients which would be applied to a PCT / US25 / 43182 22 August 2025 (22.08.2025) subject and / or a convenient fraction of such a dosage, such as one -half or one-third of such a dosage.

[0183] Formulations

[0184] In some embodiments, delivering an effective amount of a one or more chorismate metabolites or a physiologically (e.g., pharmaceutically) acceptable salt thereof to a subject comprises applying a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprising the one or more chorismate metabolites via oral, rectal, enteral, parenteral (e.g., intravenous, intramuscular, subcutaneous, intrathecal), nasal, urogenital, topical, and / or intraperitoneal application routes. In certain embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is formulated for delivery of the one or more chorismate metabolites to the gut of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is formulated for delivery of the one or more chorismate metabolites to the large intestine of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is formulated for delivery of the one or more chorismate metabolites to the colon of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is formulated for delivery of the one or more chorismate metabolites to the small intestine of a subject. In certain embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is formulated for delivery of the one or more chorismate metabolites to the small intestine and large intestine of a subject.

[0185] Pharmaceutical compositions and nutraceutical compositions described herein are physiologically acceptable (e.g., pharmaceutically acceptable) for application to human subjects (e.g., for human consumption); for example, pharmaceutical compositions and nutraceutical compositions can be understood to be sterile or undergo sterilization during preparation. The compositions (e.g., pharmaceutical compositions, nutraceutical compositions) described herein may be formulated in any suitable form for application to a human subject. Preferably, the pharmaceutical or nutraceutical composition is suitable for oral application (e.g., ingestion).

[0186] The inventors have recognized and appreciated that, in cases of oral application (e.g., ingestions) of one or more chorismate metabolites, it may be desirable for an oral dosage form to comprise a controlled release coating to facilitate targeted delivery of the one or more chorismate metabolites to a particular location within the gut of a subject (e.g., the colon, the small intestine). In some cases, targeted delivery of the one or more chorismate metabolites to a PCT / US25 / 43182 22 August 2025 (22.08.2025) particular location within the gut may enhance treatment efficacy, reduce systemic drug exposure and associated toxicity, and / or improve bioavailability.

[0187] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites described herein or a pharmaceutically acceptable salt thereof, and a targeted delivery facilitating agent. In some embodiments, the targeted delivery facilitating agent comprises one or more materials that dissolve under certain conditions. In some embodiments, a targeted delivery facilitating agent comprises one or more materials that dissolve under certain pH conditions. In some embodiments, the targeted delivery facilitating agent comprises one or more materials that are susceptible to degradation by a microbial organism.

[0188] In some embodiments, a targeted delivery facilitating agent comprises one or more materials that dissolve under certain pH conditions and / or one or more materials that are susceptible to degradation by a microbial organism.

[0189] In some embodiments, the compositions (e.g., pharmaceutical compositions, nutraceutical compositions) described herein comprise a solid dosage form comprising: a core comprising one or more chorismate metabolites, and optionally, an additional active ingredient, in an effective amount; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in the gut of a subject to whom the solid dosage form is administered. In some embodiments, the core comprises a pH-sensitive material and / or a microbe- sensitive material described herein. In some embodiments, the core comprises one or more nanoparticles (e.g., lipid nanoparticles, polymeric nanoparticles). In some embodiments, the solid dosage form further comprises a carrier (e.g., such that the core is comprised in a carrier). In some embodiments, a solid dosage form comprises one or more chorismate metabolites, and optionally, an additional active ingredient, in an effective amount; and a carrier, wherein the chorismate metabolite and optional additional active ingredient are loaded into the carrier. In some embodiments, a solid dosage form comprises a tablet, gelcap, capsule, lozenge, sachet, or other suitable solid form. In some embodiments, a core of a solid dosage form comprises a tablet, gelcap, capsule, lozenge, sachet, or other suitable form. In some embodiments, the core of a solid dosage form comprises a tablet, gelcap, capsule, lozenge, sachet, or other suitable form. In some embodiments, the solid dosage form is a microparticulate, mini-capsulate, microcapsule, mini-tab, pellet, or granule. In some embodiments, the solid dosage form is a sprinkle such that it can be combined with soft food prior and consumed. In some embodiments, a solid dosage form comprises one or more PCT / US25 / 43182 22 August 2025 (22.08.2025) chonsmate metabolites and, optionally, an additional active ingredient, loaded into an excipient. In some embodiments, a solid dosage form comprises one or more chorismate metabolites and, optionally, an additional active ingredient, loaded into a carrier.

[0190] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that is not absorbed through an intestinal wall of a subject. In some embodiments, a composition(e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier about 51% to about 99% of which carrier is not absorbed through an intestinal wall of a subject. In some embodiments, a composition comprises one or more chorismate metabolites and a carrier about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 49% of which carrier is absorbed into the blood of a subject. In some embodiments, a composition comprises one or more chorismate metabolites and a carrier that targets the one or more chorismate metabolites to an intestinal microbiome. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that specifically targets the one or more chorismate metabolites to an intestinal microbiome present in a subject and does not target the one or more chorismate metabolites to the blood of the subject. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that specifically targets the one or more chorismate metabolites to an intestinal location for absorption into the blood. In some embodiments, a carrier that specifically targets one or more chorismate metabolites to an intestinal microbiome present in a subject and does not target the one or more chorismate metabolites to the blood of the subject comprises a polymer. In some embodiments, a carrier that specifically targets one or more chorismate metabolites to an intestinal microbiome comprises a polymer comprising polyvinylpyrrolidone. In some embodiments, a carrier that specifically targets one or more chorismate metabolites to an intestinal microbiome comprises a polymer hydrogel, e.g., a polyvinylpyrrolidone (PVP) hydrogel. In some embodiments, a carrier that specifically targets the one or more chorismate metabolites to an intestinal microbiome comprises a polymer, e.g., a PVP hydrogel loaded with the one or more chorismate metabolites. The term “loaded with,” as used herein, refers to an interaction between two molecules, e.g., a polymer and one or more chorismate metabolites. The interaction can be an interaction based on hydrophilic interaction, e.g., a charge interaction, or a hydrophobic interaction. In some embodiments, a composition (e.g., a pharmaceutical PCT / US25 / 43182 22 August 2025 (22.08.2025) composition, a nutraceutical composition) comprising a polymer, e.g., a PVP hydrogel loaded with one or more chorismate metabolites, targets the one or more chorismate metabolites to a location in an intestine. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprising a polymer, e.g., a PVP hydrogel loaded with one or more chorismate metabolites targets the one or more chorismate metabolites to an intestinal location with alkaline pH. For example, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprising a polymer, e.g., a PVP hydrogel loaded with one or more chorismate metabolites may target the one or more chorismate metabolites to a distal ileum and / or colon where an alkaline pH decreases hydrogen bonds within the polymer, e.g., PVP hydrogel and hydrogen bonds between the polymer, e.g., PVP hydrogel and the one or more chorismate metabolites effectuating the release of the one or more chorismate metabolites in the distal ileum and / or colon. In some embodiments, a carrier comprising a polymer, e.g., a PVP polymer is associated with one or more chorismate metabolites through a linker. In some embodiments, a carrier comprising a polymer, e.g., a PVP polymer is associated with one or more chorismate metabolites through a non-digestible linker. In some embodiments, one or more chorismate metabolites are dispersed in a polymer, e.g., a PVP polymer. In some embodiments, one or more chorismate metabolites are present in a core, e.g., of a tablet and a polymer, e.g., a PVP polymer surrounds the tablet core.

[0191] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that releases the one or more chorismate metabolites such that the one or more chorismate metabolites are absorbed through an intestinal wall of a subject. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that releases the one or more chorismate metabolites in a small intestine. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that releases the one or more chorismate metabolites in an ileum. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) comprises one or more chorismate metabolites and a carrier that releases the one or more chorismate metabolites in a colon.

[0192] In some embodiments, a dosage form comprises a controlled release coating applied to an exterior surface of a core comprising a chorismate metabolite and optional additional active ingredient. In some embodiments, the controlled release coating is comprised in a carrier PCT / US25 / 43182 22 August 2025 (22.08.2025) comprising a chonsmate metabolite and optional additional active ingredient. In some cases, the controlled release coating provides targeted delivery of a chorismate metabolite and optional additional active ingredient (e.g., as comprised in a core) to a desired location within the GI tract, such as one or more portions of the large intestine (e.g., the colon) and / or the small intestine of a subject to whom the pharmaceutical dosage form is administered. In certain embodiments, the controlled release coating is configured to release a chorismate metabolite and optional additional active ingredient (e.g., as comprised in a core) in the large intestine (e.g., colon) of the subject. In some instances, the controlled release coating is configured to release a chorismate metabolite and optional additional active ingredient (e.g., as comprised in a core) in the small intestine of the subject.

[0193] In some embodiments, the controlled release coating consists of a single layer. In some embodiments, the controlled release coating comprises a plurality of layers. The plurality of layers may comprise two, three, four, five, or more layers. In some cases, two or more layers of the plurality of layers comprise the same material. In some cases, two or more layers of the plurality of layers comprise different materials.

[0194] In some embodiments, one or more layers of the controlled release coating comprise one or more pH-sensitive materials. A pH-sensitive material generally refers to a material configured to dissolve above or below a threshold pH value. In healthy individuals, pH values are generally low (e.g., 0.95 to 3.5) in the stomach, increase from the proximal small intestine (e.g., 5.5 to 7.0) to the distal ileum (e.g., 6.5 to 7.5), fall in the caecum (e.g., 5.5 to 7.0), and then increase in the colon (e.g., 6.0 to 7.5). In some embodiments, a pH-sensitive material is configured to resist dissolution at the relatively low pH values of the stomach and to dissolve at the relatively high pH values of the colon and / or small intestine. In certain embodiments, a pH-sensitive material is configured to dissolve at a pH of 5.5 or higher, 6.0 or higher, 6.5 higher, 7.0 or higher, or 7.5 or higher.

[0195] In some embodiments, the one or more pH-sensitive materials comprise a pH-sensitive polymer. In certain cases, a pH-sensitive polymer comprises one or more of the following monomers: methacrylic acid, methyl methacrylate, methyl acrylate, ethyl acrylate, acrylic acid, dimethylaminoethyl methacrylate, butyl methacrylate, and N-isopropylacrylamide. Non-limiting examples of suitable pH-sensitive polymers include copolymers of methacrylic acid and methyl methacrylate, copolymers of methacrylic acid and ethyl acrylate, copolymers of methyl acrylate, methyl methacrylate, and methacrylic acid, an aminoalkyl methacrylate copolymer, cellulose acetate phthalate (“CAP”), hydroxypropyl methylcellulose phthalate (“HPMCP”), PCT / US25 / 43182 22 August 2025 (22.08.2025) hydroxypropyl methylcellulose acetate succinate ( ‘HPMC-AS ), poly(N-isopropylacrylamide) (“PNI-PAM”), EUDRAGIT® S, EUDRAGIT® FS, EUDRAGIT® L, and Kollicoat® MAE 100P.

[0196] In some cases, one or more layers of the controlled release coating comprise a microbesensitive material. In some cases, a microbe- sensitive material is susceptible to degradation by one or more microbial organisms residing in a portion of the GI tract (e.g., the colon). Nonlimiting examples of suitable microbe-sensitive materials include amylose, lactulose, amylopectin, pectin, guar gum, locust bean gum, inulin, chitosan, arabinoxylans, agave fructans, alginate, chondroitin sulfate, dextran, and cyclodextrin.

[0197] In certain embodiments, the controlled release coating comprises a layer comprising a pH-sensitive material and a microbe- sensitive material. In certain embodiments, the controlled release coating comprises one or more layers comprising a pH-sensitive material and one or more layers comprising a microbe-sensitive material. In certain embodiments, the controlled release coating comprises one or more layers comprising a first pH-sensitive material and one or more layers comprising a second pH-sensitive material. In some instances, the controlled release coating comprises one, two, three, four, five, or more pH-sensitive materials. In certain embodiments, the controlled release coating comprises one or more layers comprising a first microbe- sensitive material and one or more layers comprising a second microbe-sensitive material. In some instances, the controlled release coating comprises one, two, three, four, five, or more microbe-sensitive materials. In some cases, the controlled release coating comprises one or more hydrophilic layers and one or more lipophilic layers. In some cases, the controlled release coating comprises one or more layers formed from an aqueous solution and one or more layers formed from an organic solution.

[0198] In certain embodiments, the controlled release coating comprises a rupturable film. In certain embodiments, the controlled release coating comprises a hydrogel plug configured to swell upon exposure to moisture and rupture the coating. In some instances, the hydrogel plug may be covered by a cap comprising a pH-sensitive material and / or a microbe-sensitive material.

[0199] In solid dosage forms comprising a core, components of the core (e.g., one or more chorismate metabolites) may be mixed with at least one inert, physiologically (e.g., pharmaceutically) acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and / or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, PCT / US25 / 43182 22 August 2025 (22.08.2025) and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In some embodiments, a solid dosage form may include a buffering agent.

[0200] The inventors have also recognized and appreciated that, for some subjects (e.g., children, subjects with ASD), it may be desirable for an oral dosage form to be provided in a drinkable dosage form; for example, a solution, an emulsion, a beverage, a suspension, a syrup, or a powder (e.g., in a sachet) that can be combined (e.g., dissolved) with a liquid for oral application (e.g., ingestion). In some embodiments, the drinkable dosage form comprises: one or more chorismate metabolites and optionally, an additional active ingredient; and a suitable adjuvant. An adjuvant suitable for a drinkable dosage form may be any adjuvant which can be safely consumed by a subject, for example, a diluent (e.g., water), solvents or suspending media (e.g., fixed oils such as synthetic monoglycerides, diglycerides, polyethylene glycols, glycerin, propylene glycol), antioxidants (e.g., ascorbic acid, sodium bisulfite), chelating agents (e.g., ethylenediaminetetraacetic acid), buffers (e.g., acetates, citrates, phosphates). In some embodiments, the drinkable dosage form is a powder that can be combined with a liquid or soft food, and comprises: one or more chorismate metabolites and optionally, an additional active ingredient. In some embodiments, the drinkable dosage form further comprises one or more buffers (e.g., acetates, citrates, phosphates). In some embodiments, the drinkable dosage form further comprises an agent for adjusting tonicity (e.g. sodium chloride, dextrose). Typically, a drinkable dosage further comprises one or more flavoring agents or sweeteners.

[0201] In some embodiments, a dosage form (e.g., an oral dosage form) comprises one or more acceptable liquid or gel carriers. In some embodiments, the one or more acceptable liquid or gel carriers are physiologically acceptable liquid or gel carriers. In some embodiments, the liquid or gel carriers include water, saline solutions, alcohol solutions, dextrose solutions, glycerol solutions, and oils, including but not limited to petroleum oil (e.g., mineral oil), vegetable oil (e.g., peanut oil, soybean oil, sesame oil), animal oil, and oil of synthetic origin.

[0202] In some embodiments, a dosage form (e.g., a solid dosage form, an oral dosage form) comprises one or more acceptable excipients. In some cases, the one or more acceptable excipients are physiologically acceptable excipients. In some embodiments, the physiologically acceptable excipients comprise one or more physiologically acceptable carriers, buffers, salts, PCT / US25 / 43182 22 August 2025 (22.08.2025) inert diluents or filling agents, binders, stabilizers, emulsifiers, disintegrants, diluents, lubricants, additives, preservatives, taste maskers, colorants, adjuvants, dispersing and / or granulating agents, surface active agents and / or, oils, and / or other agents. In some embodiments, a physiologically acceptable excipient is a pharmaceutically acceptable excipient.

[0203] Non-limiting examples of suitable physiologically (e.g., pharmaceutically) acceptable excipients (e.g., carriers) include sugars (e.g., sucrose, lactose), polysaccharides (e.g., cellulose and derivatives thereof, starches, dextran), sugar alcohols (e.g., xylitol, sorbitol, mannitol), gelatin, polymers (e.g., polyvinylpyrrolidone, polyethylene glycol, polyacrylates), colloidal silicon dioxide, calcium carbonate, calcium phosphate, calcium hydroxide, magnesium stearate, sodium lauryl sulfate, and sodium acetate. In some embodiments, a carrier comprises a sugar (e.g., sucrose, lactose), polysaccharide (e.g., cellulose and derivatives thereof, starches, dextran), sugar alcohol (e.g., xylitol, sorbitol, mannitol), gelatin, polymer (e.g., polyvinylpyrrolidone, polyethylene glycol, polyacrylates), colloidal silicon dioxide, calcium carbonate, calcium phosphate, calcium hydroxide, magnesium stearate, sodium lauryl sulfate, sodium acetate, or a combination thereof. Excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and perfuming agents may also be present in the composition. Relative amounts of the active ingredients (e.g., one or more chorismate metabolites, and, optionally an additional active ingredient), the physiologically (e.g., pharmaceutically) acceptable excipient (e.g., carrier), and / or any additional ingredients in a composition (e.g., pharmaceutical composition, nutraceutical composition) described herein will vary, depending upon the identity, size, and / or condition of the subject treated and further depending upon the route by which the composition is to be administered. The composition may comprise between 0.1% and 100% (w / w) active ingredient.

[0204] Other dosage forms are also contemplated herein. For example, in certain embodiments, a dosage form is formulated as an aqueous solution, an alcoholic solution, an emulsion, a gel, a cream, and / or an ointment for rectal application. In certain embodiments, rectal application is achieved through the use of an enema, a suppository, a tube, or an aerosol with an attachment that is inserted into the anus. In some instances, the solid form is formulated as a suppository (e.g., for rectal application).

[0205] In certain embodiments, a dosage form is formulated as an injection for intraperitoneal, intramuscular, subcutaneous, intravenous, or intrathecal application. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0206] Kits

[0207] Also encompassed by the disclosure are kits (e.g., pharmaceutical packs). The kits provided may comprise a pharmaceutical composition or compound described herein and a container (e.g., a vial, ampule, bottle, syringe, and / or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of a pharmaceutical composition or compound described herein. In some embodiments, the pharmaceutical composition or compound described herein provided in the first container and the second container are combined to form one unit dosage form.

[0208] In one aspect, provided herein a kit comprising: a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or a pharmaceutical composition provided herein; and instructions for using the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or the pharmaceutical composition.

[0209] In certain embodiments, provided are kits including a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, the kits are useful for treating a disease (e.g., neurological or neurodevelopmental disorder) in a subject in need thereof. In certain embodiments, the kits are useful for preventing a disease (e.g., neurological or neurodevelopmental disorder) in a subject in need thereof. In certain embodiments, the kits are useful for reducing the risk of developing a disease (e.g., neurological or neurodevelopmental disorder) in a subject in need thereof.

[0210] In some embodiments, the kits provided may comprise a nutraceutical composition or compound described herein and a container (e.g., a vial, ampule, bottle, syringe, and / or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a physiologically acceptable excipient for dilution or suspension of a nutraceutical composition or compound described herein. In some embodiments, the nutraceutical composition or compound described herein provided in the first container and the second container are combined to form one unit dosage form.

[0211] In one aspect, provided herein a kit comprising: a compound described herein, or a physiologically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or a nutraceutical composition provided herein; and instructions for using the compound, or a physiologically acceptable salt, solvate, PCT / US25 / 43182 22 August 2025 (22.08.2025) hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, or the nutraceutical composition.

[0212] Thus, in certain embodiments, provided are kits including a first container comprising a compound or nutraceutical composition described herein. In certain embodiments, the kits are useful for providing one or more beneficial effects to a subject (e.g., a neurotypical subject.

[0213] In certain embodiments, a kit described herein further includes instructions for using the kit (e.g., for use in therapy or for ingestion in the form of a nutraceutical). A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information (e.g., for use in therapy or for ingestion in the form of a nutraceutical). In certain embodiments, the kits and instructions provide for treating a disease (e.g., neurological or neurodevelopmental disorder) in a subject in need thereof. In certain embodiments, the kits and instructions provide for preventing a disease (e.g., neurological or neurodevelopmental disorder) in a subject in need thereof. In certain embodiments, the kits and instructions provide for reducing the risk of developing a disease (e.g., neurological or neurodevelopmental disorder) in a subject in need thereof. A kit described herein may include one or more additional pharmaceutical and / or nutraceutical agents described herein as a separate composition.

[0214] In another aspect, provided are kits including a first container comprising a first composition described herein and a second container comprising a second composition described herein. In another aspect, provided are kits including a first container comprising a first composition comprising one or more chorismate metabolites and a second container comprising a second composition comprising one more chorismate metabolites. In some embodiments, the first composition and the second composition are different. In some embodiments, the first composition comprises at least two chorismate metabolites (e.g., a first chorismate metabolite and a second chorismate metabolite) and the second composition comprises at least two chorismate metabolites (e.g., a third chorismate metabolite and a fourth chorismate metabolite). In some embodiments, the first composition comprises at least a first chorismate metabolite and second chorismate metabolite; and the second composition comprises at least a third chorismate metabolite and a fourth chorismate metabolite. In some embodiments, the chorismate metabolites of the first composition and the chorismate metabolites of the second composition are different. In some embodiments, the chorismate metabolites of the first composition and the chorismate metabolites of the second composition are the same, but present PCT / US25 / 43182 22 August 2025 (22.08.2025) in the compositions in different ratios (e.g., molar ratio). As a non-limiting example, the first chorismate metabolite and the third chorismate metabolite may both be Vitamin K and the second chorismate metabolite and the fourth chorismate metabolite may both be L-tryptophan; however, the first composition may comprise a ratio of 1:2 Vitamin K:tryptophan, while the second composition comprises a ratio of 1:4 Vitamin K:tryptophan. In some embodiments, the kits comprise instructions for combining the compositions to prepare a pharmaceutical composition. In some embodiments, the kits comprise instructions for combining the compositions to prepare a nutraceutical composition. In some embodiments, the kits further include instructions for using the kit or pharmaceutical and / or nutraceutical compositions prepared according to its instructions.

[0215] Methods of Use

[0216] In some aspects, provided in the present disclosure are methods comprising providing (e.g., administering, applying) a composition comprising a chorismate metabolite to a subject. In some embodiments, providing a composition to a subject comprises applying the composition to the subject. In some embodiments, providing a composition to a subject comprises administering the composition to the subject. In some aspects, provided in the present disclosure are methods comprising providing (e.g., administering) a chorismate metabolite and an additional active ingredient to a subject.

[0217] In some embodiments, methods provided herein comprise a method of providing a composition as described herein to a neurotypical subject, wherein the composition provides one or more beneficial effects to the neurotypical subject. In some embodiments, methods provided herein comprise a method of enhancing one or more cognitive and / or behavioral functions in a neurotypical subject, the method comprising providing a composition (e.g., a nutraceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of enhancing one or more cognitive and / or behavioral functions in a neurotypical subject, the method comprising applying a composition a nutraceutical composition described herein to the subject. In some embodiments, methods provided herein comprise a method of enhancing one or more cognitive and / or behavioral functions in a neurotypical subject, the method comprising providing a composition (e.g., a nutraceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., a nutraceutical composition) to the subject (e.g., self-application). PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0218] In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject in need thereof (e.g., subject exhibiting one or more signs or symptoms of a neurological disorder). In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject in need thereof (e.g., subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising providing a composition (e.g., a pharmaceutical composition, a nutraceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject in need thereof (e.g., subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising administering pharmaceutical composition described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject in need thereof (e.g., subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising applying a nutraceutical composition described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject in need thereof (e.g., subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising providing a composition (e.g., a pharmaceutical composition, a nutraceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition, the nutraceutical composition) to the subject (e.g., selfadministration).

[0219] In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder). In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising providing a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising administering a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more prophylactic effects to a subject having or at risk of developing a neurological PCT / US25 / 43182 22 August 2025 (22.08.2025) disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising providing composition (e.g., a pharmaceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-administration).

[0220] In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder). In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising providing a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising administering a composition (e.g., a pharmaceutical composition) described herein to the subject. In some embodiments, methods provided herein comprise a method of providing one or more therapeutic effects to a subject having or at risk of developing a neurological disorder (e.g., a subject exhibiting one or more signs or symptoms of a neurological disorder), the method comprising providing composition (e.g., a pharmaceutical composition) described herein to the subject, for example, along with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-administration).

[0221] In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or suspected of having a neurological disorder. In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or at risk of developing a neurological disorder, the method comprising providing a composition (e.g., a pharmaceutical composition) to the subject. In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or at risk of developing a neurological disorder, the method comprising administering a composition (e.g., a pharmaceutical composition) to the subject. In some embodiments, methods provided herein comprise methods of treating (e.g., providing one or more therapeutic effects) to a subject having or at risk of developing a neurological disorder, the method comprising providing composition (e.g., a pharmaceutical composition) to the subject, for example, along PCT / US25 / 43182 22 August 2025 (22.08.2025) with instructions for administering the composition (e.g., the pharmaceutical composition) to the subject (e.g., self-application, self-administration).

[0222] In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder, the method comprising providing a composition (e.g., nutraceutical composition, pharmaceutical composition) to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder, the method comprising administering a pharmaceutical composition to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder, the method comprising applying a nutraceutical composition to the subject. In some embodiments, methods provided herein comprise providing a composition to a subject having or at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder, for example, along with instructions for applying and / or administering the composition (e.g., a pharmaceutical composition, a nutraceutical composition) to the subject (e.g., self-application, self-administration) .

[0223] In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing ASD, the method comprising providing a composition (e.g., a pharmaceutical composition, a nutraceutical composition) to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing ASD, the method comprising PCT / US25 / 43182 22 August 2025 (22.08.2025) administering a pharmaceutical composition to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing ASD, the method comprising applying a nutraceutical composition to the subject. In some embodiments, methods provided herein comprise a method of providing one or more beneficial effects to a subject having or at risk of developing ASD, the method comprising providing the composition (e.g., a pharmaceutical composition, a nutraceutical composition) to the subject, for example, along with instructions for applying and / or administering the composition to the subject (e.g., self-application, self-administration).

[0224] Subjects

[0225] According to some embodiments, methods provided herein comprise providing (e.g., administering, applying) a composition described herein to a subject.

[0226] In some embodiments, the subject has, is suspected of having, or is at risk of developing a neurological disorder. In some embodiments, the subject exhibits one or more signs or symptoms of a neurological disorder. In some embodiments, a subject at risk of developing a neurological disorder is a subject that has been identified to be at risk of the neurological disorder by a qualified healthcare professional. In some embodiments, a subject at risk of developing a neurological disorder is a subject that has been identified to be at risk of the neurological disorder using a predictive gene detection test and / or biomarker evaluation. In some embodiments, a subject at risk of developing a neurological disorder has a family member (e.g., mother, father, sibling, sister, aunt, uncle, grandparent) who has been diagnosed with the neurological disorder. In some embodiments, a subject at risk of developing a neurological disorder is a descendent of a relative (e.g., mother, father, grandparent, great grandparent) who has been diagnosed with a neurological disorder or is a carrier of a gene associated with the neurological disorder.

[0227] In some embodiments, the subject is neurotypical. As used herein, the term “neurotypical” refers to someone who has not been deemed by a qualified healthcare professional to have a neurological disorder, is not suspected by a qualified healthcare professional to have a neurological disorder, and / or is not at risk of developing a neurological disorder.

[0228] In some embodiments, a subject at risk of developing a neurological disorder has an altered level of a chorismate metabolite and / or a molecule within the chorismate metabolic pathway relative to the level in one or more neurotypical individuals. In some embodiments, a PCT / US25 / 43182 22 August 2025 (22.08.2025) subject having or suspected of having a neurological disorder has an altered level of a chorismate metabolite and / or a molecule within the chorismate metabolic pathway relative to the level in one or more neurotypical individuals. In some embodiments, a neurotypical subject has an altered level of a chorismate metabolite and / or a molecule within the chorismate metabolic pathway relative to the level in one or more different neurotypical individuals.

[0229] In some embodiments, the subject has, is suspected of having, or is at risk of developing a neurodevelopmental disorder. In some embodiments, the subject exhibits one or more signs or symptoms of a neurodevelopmental disorder. In some embodiments, the subject has, is suspected of having, is at risk of developing, or exhibits one or more signs or symptoms of autism spectrum disorder (ASD; e.g., classic autism, Asperger syndrome), attention deficit disorder, Fragile X syndrome, Rett syndrome, pervasive developmental disorder not otherwise specified (PDD-N08), childhood disintegrative disorder (CDD), tuberous sclerosis, Fragile X syndrome, Rett syndrome, Angelman syndrome, Dupl5q syndrome, 22ql3.3 Deletion syndrome, Prader-Willi syndrome, velocardiofacial syndrome, Smith-Lemli-Opitz syndrome, or any combination thereof. In some embodiments, the subject has, is suspected of having, or is at risk of developing ASD. In some embodiments, the subject has, is suspected of having, or is at risk of developing a chorismate subtype of ASD.

[0230] In some embodiments, the subject has, is suspected of having, or is at risk of developing a neuropsychiatric disorder. In some embodiments, the subject exhibits one or more signs or symptoms of a neuropsychiatric disorder. In some embodiments, the subject has, is suspected of having, is at risk of developing, or exhibits one or more signs or symptoms of anxiety disorder, attention deficit disorder, bipolar disorder, cognitive disorder, delirium, dementia, depression, dissociative disorders, eating disorders (e.g., anorexia nervosa), impulse-control disorders, mood disorders, mania, obsessive-compulsive disorders, personality disorders (e.g., borderline personality disorder), psychosis, psychotic disorders (e.g., schizophrenic disorders), post- traumatic stress disorders, sexual disorders, sleep disorders, somatoform disorders, substance abuse disorders (e.g., alcoholism, drug addiction), or any combination thereof.

[0231] In some embodiments, the subject has, is suspected of having, or is at risk of developing a neurodegenerative disorder. In some embodiments, the subject exhibits one or more signs or symptoms of a neurodegenerative disorder. In some embodiments, the subject has, is suspected of having, is at risk of developing, or exhibits one or more signs or symptoms of Alzheimer's disease (AD), preclinical Alzheimer's disease (PCAD), Parkinson's disease (PD), Huntington's disease (HD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS, e.g., familial PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0232] ALS and sporadic ALS), multiple sclerosis (MS), vascular dementia (cerebral amyloid angiopathy and stroke), dementia with Lewy bodies, HIV dementia, age-associated memory impairment (AAMI), age-related cognitive decline (ARCD), Batten disease, Creutzfeldt-Jakob disease, and cognitive impairment no dementia (CIND).

[0233] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In certain embodiments, the subject is human male. In certain embodiments, the subject is human female. The subject may be from any geographical location. In certain embodiments, the subject is from North America (e.g., the United States), Asia (e.g., China, South Korea), Europe (e.g., Italy), and / or South America (e.g., Ecuador).

[0234] The subject may be of any age. In certain embodiments, the subject is a child (e.g., 17 years old or younger). In certain embodiments, the subject is an adult (e.g., 18 years old or older). In some embodiments, the subject has an age in a range from 1-5 years old, 1-7 years old, 1-10 years old, 1-15 years old, 1-17 years old, 1-18 years old, 1-21 years old, 1-50 years old, 1- 70 years old, 1-100 years old, 2-7 years old, 2-10 years old, 2-15 years old, 2-17 years old, 2-18 years old, 2-21 years old, 2-50 years old, 2-70 years old, 2-100 years old, 5-10 years old, 5-15 years old, 5-17 years old, 5-18 years old, 5-21 years old, 5-50 years old, 5-70 years old, 5-100 years old, 10-15 years old, 10-17 years old, 10-18 years old, 10-21 years old, 10-50 years old, 10-70 years old, 10-100 years old, 15-21 years old, 15-50 years old, 15-70 years old, 15-100 years old, 18-50 years old, 18-70 years old, 18-100 years old, 21-50 years old, 21-70 years old, 21-100 years old, 50-70 years old, 50-100 years old, or 70-100 years old.

[0235] Methods of Administration

[0236] In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is provided (e.g., administered, applied) chronically. In certain embodiments, the composition (e.g., a pharmaceutical composition, a nutraceutical composition) is provided (e.g., administered, applied) over a period of at least 1 month, at least 3 months, at least 6 months, at least 9 months, at least 1 year, at least 3 years, at least 5 years, at least 10 years, or at least 20 years. In certain embodiments, the composition (e.g., a pharmaceutical composition, a nutraceutical composition) is provided (e.g., administered, applied) over a period of 1 to 3 months, 1 to 6 months, 1 to 9 months, 1 month to 1 year, 1 month to 3 years, 1 month to 5 years, 1 month to 10 years, 1 month to 20 years, 3 to 6 months, 3 to 9 months, 3 months to 1 year, 3 months to 3 years, 3 months to 5 years, 3 months to 10 years, 3 months to 20 years, 6 to 9 months, 6 months to 1 year, 6 months to 3 years, 6 months to 5 years, 6 months to 10 years, 6 PCT / US25 / 43182 22 August 2025 (22.08.2025) months to 20 years, 9 months to 1 year, 9 months to 3 years, 9 months to 5 years, 9 months to 10 years, 9 months to 20 years, 1 to 3 years, 1 to 5 years, 1 to 10 years, 1 to 20 years, 3 to 5 years, 3 to 10 years, 3 to 20 years, 5 to 10 years, 5 to 20 years, or 10 to 20 years. In some embodiments, a composition (e.g., a pharmaceutical composition, a nutraceutical composition) is provided (e.g., administered, applied) to a subject daily, weekly, monthly, or at shorter or longer time intervals.

[0237] In some embodiments, a nutraceutical composition is provided (e.g., applied) to a subject in an effective amount, for example, in an amount effective to provide one or more beneficial effects.

[0238] In some embodiments, a pharmaceutical composition is provided (e.g., administered) to a subject until one or more signs or symptoms of neurological or neurodevelopmental disorder (e.g., ASD) are alleviated. In some embodiments, a pharmaceutical composition (e.g., a prophylactic pharmaceutical composition) is provided (e.g., administered) to a subject in an effective amount, for example in an amount sufficient to prevent (e.g., delays the onset of) or reduce the likelihood of one or more signs or symptoms of ASD and / or of comorbidities of ASD. In some embodiments, a pharmaceutical composition (e.g., a therapeutic pharmaceutical composition, a prophylactic pharmaceutical composition) is provided (e.g., administered) to a subject in an amount sufficient to reduce a risk of a subject developing ASD. In some embodiments, a pharmaceutical composition (e.g., a therapeutic pharmaceutical composition) is provided (e.g., administered) to a subject in an amount sufficient to alleviate (e.g., reducing or eliminating, slowing the progression) or treat one or more signs or symptoms of ASD and / or of comorbidities of ASD.

[0239] The pharmaceutical dosage forms described herein can be provided (e.g., administered) concurrently with, prior to, or subsequent to one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include, for example, therapeutically active agents and prophy tactically active agents. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved for human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. In certain embodiments, the additional pharmaceutical agent is a pharmaceutical agent useful for treating and / or preventing a disease (e.g., neurological or PCT / US25 / 43182 22 August 2025 (22.08.2025) neurodevelopmental disorder). Each additional pharmaceutical agent may be provided (e.g., administered) at a dose and / or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be provided (e.g., administered) together with each other and / or with the compound or composition described herein in a single dose or composition or provided (e.g., administered) separately in different doses or compositions. The particular combination to employ in a regimen will take into account compatibility of the compound described herein with the additional pharmaceutical agent(s) and / or the desired therapeutic and / or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agent(s) in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually.

[0240] In some embodiments, a method comprises providing (e.g., applying, administering) a composition described herein to a subject.

[0241] In some embodiments, a method comprises inducing one or more beneficial effects in a subject. In some embodiments, inducing one or more beneficial effects in a subject comprises providing (e.g., applying) a nutraceutical composition described herein to a subject. In some embodiments, inducing one or more beneficial effects in a subject comprises providing (e.g., administering) a pharmaceutical composition described herein to a subject. In some embodiments, providing a composition (e.g., a nutraceutical composition, a pharmaceutical composition) to the subject modulates a level of a molecule within a chorismate metabolic pathway in the subject. In some embodiments, modulating the level comprises increasing the level. In some embodiments, modulating the level comprises decreasing the level. In some cases, the level is modulated in the gut of the subject.

[0242] In some embodiments, a method comprises inducing one or more prophylactic effects in a subject. In some embodiments, inducing one or more prophylactic effects in a subject comprises administering a pharmaceutical composition described herein to a subject. In some embodiments, a method comprises inducing one or more therapeutic effects in a subject. In some embodiments, inducing one or more therapeutic effects in a subject comprises administering a pharmaceutical composition described herein to a subject. In some embodiments, a method comprises treating a subject. In some embodiments, the method of treating a subject comprises administering a pharmaceutical composition (e.g., a therapeutic composition) described herein to the subject. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0243] In some embodiments, providing a composition to the subject modulates a level of a molecule within a chorismate metabolic pathway in the subject to alleviate one or more signs or symptoms of ASD and / or of comorbidities of ASD or to reduce the risk of developing ASD. In some embodiments, modulating the level comprises increasing the level. In some embodiments, modulating the level comprises decreasing the level. In some cases, the level is modulated in the gut of the subject.

[0244] Methods of Determining Altered Levels of Chorismate Metabolites

[0245] In some embodiments, a composition provided herein is provided (e.g., applied, administered) to a subject who has been determined to have an altered level of a chorismate metabolite and / or a molecule within the chorismate metabolic pathway relative to the level in one or more neurotypical individuals. In some embodiments, determining the level of a chorismate metabolite and / or the molecule within the chorismate metabolic pathway comprises measuring the level of the molecule within the chorismate metabolic pathway (e.g., using HPLC, LC-MS, GC-MS, and / or MALDI-TOF). In some embodiments, the level is determined from a sample of the subject. In some embodiments, a level of a chorismate metabolite and / or a molecule within the chorismate metabolic pathway from a subject is determined from a sample. The sample may be any sample described herein (e.g., a fecal sample, a gastrointestinal sample, a serum sample, a CSF sample).

[0246] In some cases, a sample obtained from the subject may comprise an abundance of one or more molecules indicating that the subject may be likely to respond to a chorismate-based intervention. In certain cases, the one or more molecules and / or microbial features comprise one or more metabolites of the superpathway of chorismate metabolism, e.g., a metabolite in Table 1. In some cases, a sample obtained from the subject may comprise an abundance of one or more genes (e.g., one or more genes within the superpathway of chorismate metabolism) indicating that the subject may be likely to respond to a chorismate-based intervention.

[0247] In some embodiments, methods described herein comprise analyzing a sample obtained from a subject to evaluate one or more characteristics of a microbiome (e.g., level of one or more chorismate metabolites) of the subject. In some cases, the one or more characteristics comprise the identity of one or more microbes detected within the microbiome and / or the amounts or relative amounts of one or more microbes detected within the microbiome.

[0248] In some embodiments, the sample is a fecal sample. In certain embodiments, obtaining the sample comprises collecting a fecal sample (e.g., collecting a stool sample, swabbing a rectal PCT / US25 / 43182 22 August 2025 (22.08.2025) cavity). In some embodiments, the sample is a gastrointestinal sample. In certain cases, a gastrointestinal sample comprises a gastric aspirate, biopsy (e.g., mucosal biopsy, gastric tissue biopsy), intestinal fluid, endoscopic brush, and / or laser capture microdissection sample. In some embodiments, obtaining the sample from a subject comprises performing a biopsy, endoscopy, and / or colonoscopy on the subject. In some embodiments, the sample is a serum, cerebrospinal fluid (CSF), urine, buccal, nasal, or salivary sample. In some embodiments, obtaining the sample from a subject comprises collecting a serum sample, performing a spinal tap on the subject, collecting a urine sample, and / or swabbing a cheek, throat, and / or nasal cavity of the subject.

[0249] In some cases, the microbiome may be a microbiome of the subject’s gastrointestinal tract (e.g., a gut microbiome that comprises gut microbiota). In some embodiments, the sample may represent characteristics of the subject’s gastrointestinal tract. In some instances, the sample is a fecal sample. In some instances, the sample is a gastrointestinal sample. In certain cases, the gastrointestinal sample is taken from the gastrointestinal tract (e.g., the lower gastrointestinal tract, the upper gastrointestinal tract). The sample may be obtained during any suitable procedure, including but not limited to colonoscopy, endoscopy, swabbing, or brushing a part of the gastrointestinal tract.

[0250] Some embodiments may relate to microbiomes for other parts of a subject’s anatomy (e.g., sinuses, skin, lungs, oral mucosa, or other). Any of the previously-described techniques for obtaining samples may be used, when medically appropriate, for obtaining samples from these other portions of a subject’s anatomy. Samples obtained may be prepared and then the microbes within them analyzed to determine microbial features. In some cases, embodiments may relate to microbiome products (e.g., chorismate and its metabolites) present in other parts of a subject’s anatomy (e.g., blood, brain, etc.).

[0251] The level of the molecule and / or the microbial feature in the sample may be measured according to any method known in the art. Non-limiting examples of suitable methods include HPLC, LC-MS, GC-MS, and matrix-assisted laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF). In certain embodiments, the level of the microbial feature in the sample may be measured by plating at least a portion of the sample on different media and / or under different conditions to evaluate microbial growth and identify one or more microbial organisms present in the sample. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0252] EXAMPLES

[0253] Example 1. Chorismate Metabolic Pathways are Specifically Implicated in Autism Spectrum Disorder

[0254] In this Example, the ASD microbiome was explored using chorismate-centered multi- omic analyses. Datasets of microbiome data from 7,457 individuals with Autism Spectrum Disorder (ASD) were curated and systematically reprocessed across published cohorts and repositories (see “Literature search strategy” below). The ASD dataset included 4,178 fecal ‘omic profiles from 2,875 individuals spanning 26 cohorts, predominantly utilizing 16S rRNA gene amplicon sequencing (16S) data, with five cohorts containing shotgun metagenomic (MGX) data. For validation, a series of fecal samples per subject from a new ASD cohort were also assessed, generating 16S, shotgun metagenomics, and metabolomics (MBX) data.

[0255] Datasets were divided by cohort and study-design factors, and features were ranked by the frequency of their significant taxonomic associations. Based on recognition that the taxonomy alone does not fully explain microbiome function, a predictive functional profiling approach was employed, using 16S rRNA data to infer functional abundances. ASD’s most robust features emerged when pathway data were analyzed (not shown), suggesting that function-based analyses could better capture ASD-related microbiome changes, and emphasizing the need to focus on metabolite pathways rather than individual taxa in ASD research.

[0256] When exploring metabolic relationships between top-ranked pathways, 8 of the top 22 ASD-implicated metabolic pathways were found to be related to chorismate (FIG. 3A). Chorismate, produced via the shikimate pathway in bacteria and plants (e.g., as shown in FIG. 1), is a precursor for vital metabolites, such as aromatic amino acids (tryptophan, L-tyrosine and L-phenylalanine), folate (vitamin B9), menaquinols (bacterial electron transport carriers and vitamin K) and quinols (an electron-rich form of coenzyme Q10), and siderophores like enterobactin (e.g., as shown in FIG. 2). Pathways were categorized based on their connections to chorismate and its derivatives, and applied gene-set enrichment analysis. This analysis revealed a marked enrichment of chorismate-related pathways in ASD (FDR q-val=0), which persisted across the categorical splitting approach and under various statistical thresholds (FIG. 3B).

[0257] Enzyme abundances and microbial source of genes within the ASD cohorts containing metagenomics data were also analyzed, and the tryptophan biosynthesis pathway, derived from PCT / US25 / 43182 22 August 2025 (22.08.2025) chonsmate, was found to exhibit the largest number of significantly reduced enzymes in ASD (not shown). Overall, chorismate-related enzymes were widely distributed across microbial taxa, suggesting a broad microbial influence on the depletion of chorismate-derived metabolites.

[0258] To directly measure chorismate and its derivatives, MBX was conducted on ASD stool samples. Chorismate itself was undetectable, likely due to a rapid microbial metabolism, but its downstream metabolites were significantly depleted in ASD, suggesting a deficiency in chorismate-derived compounds (FIG. 3C). Key metabolites identified included tetrahydrofolate, shikimate, L-tyrosine, L-tryptophan, tyramine, dopamine, 3-indolepropionic acid, p- hydroxyphenyllactic acid, and / / YUM- ferulic acid, all of which were found reduced alongside ASD symptoms (FIGs. 4A-4N). Of note, distant metabolites further downstream of chorismate, such as riboflavin, hypoxanthine, and xanthurenic acid, were also depleted and correlated with multiple ASD-related behaviors (FIG. 3D; FIGs. 5A-5E). These findings collectively point to an impact of chorismite-derived metabolites on ASD pathology.

[0259] Methods

[0260] Patient recruitment, evaluation, and sample collection

[0261] Subjects were screened for their eligibility for the study based on meeting the criteria for one of three study groups: (1) Subjects diagnosed with ASD according to DSM-5 criteria gathered by an experienced clinician, (2) Siblings of the ASD subject, and (3) Control subjects not living in the same household as an ASD individual. ASD subjects were required to be of 3 to 14 years old with no neurogenetic disorders known to be associated with ASD and IQ > 50 according to the Developmental Profile - 4th Edition (DP-4; for subjects 3-5 years old) or Wechsler Abbreviated Scale of Intelligence Scale-Second edition (WASI-II; for subjects 6-14 years old). Siblings of ASD subjects were required to be continuously living in the same household as the ASD subject for the prior 6 months, be of the age 3 to 21 years old, and be of IQ > 85. Control subjects not living with an ASD individual were required to be 3 to 14 years of age with an IQ > 85. All subjects were assessed by DSM-5, SCQ, WASI-II or DP-4 while additional measurements were taken on ASD subjects including RBS-R, SPS, ABC-2, CCC, SRS-2. Further questionnaires were collected prior to sample collection on patient demographics, medical history, birth conditions, medications, nutrition and environmental exposures. The primary site for patient recruitment and assessment was the Lurie Center of PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0262] Autism (Lexington, MA), where IRB approval was obtained under protocol # 2021P001383 and clinicians were trained on the study protocol before patient recruitment.

[0263] Subjects were requested to provide 3 stool samples collected at least one to two weeks apart from the preceding sample. Stool was collected and immediately frozen in a household

[0264] 5 freezer, then delivered to the sponsors laboratory on dry ice within 72 hours of sample collection. Stool samples were stored at -80°C before sample processing.

[0265] Fecal sample processing for sequencing

[0266] A shared DNA extraction for 16S rRNA and Metagenomic (MGX) sequencing was performed including spike-in organisms for the ability to optionally estimate the absolute quantification of microbes. Stool was measured to 250 mg and 20 pL of Spikein 1- High Molecular Weight (Zymo) was added to each sample. DNA from samples was isolated using the QIAGEN DNeasy PowerSoil Pro Kit, according to the manufacturer’s protocol. DNA samples were quantified using Qubit 4 fluorometer and QubitTM dsDNA HS Assay Kit (Thermofisher Scientific) or Picogreen (Invitrogen).

[0267] 15 16S rRNA library preparation and sequencing

[0268] For 16S rRNA amplicon sequencing, 5ng of isolated genomic DNA was sampled. Libraries were constructed by amplification via PCR with primers covering the V3-V4 region (341F & 805R). Sequencing was performed on an Illumina Miseq platform 2x250bp. Demultiplexed fastq files were downloaded from CosmosID-HUB and processed through the 16S processing pipeline described below for consistency.

[0269] Shotgun metagenomic library preparation and sequencing

[0270] For human fecal samples, DNA libraries were prepared using the Nextera XT DNA Library Preparation Kit (Illumina) and IDT Unique Dual Indexes with total DNA input of 1 ng. Genomic DNA was fragmented using a proportional amount of Illumina Nextera XT

[0271] 25 fragmentation enzyme. Unique dual indexes were added to each sample followed by 12 cycles of PCR to construct libraries. DNA libraries were purified using AMpure magnetic Beads (Beckman Coulter) and eluted in QIAGEN EB buffer. DNA libraries were quantified using Qubit 4 fluorometer and Qubit dsDNA HS Assay Kit. Libraries were then sequenced to an average depth of 20 million reads per sample on the Illumina NovaSeq platform 2xl50bp. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0272] Literature search strategy and selection cntena

[0273] A systematic literature search was implemented through the PubMed database to identify applicable studies assessing the gut microbiome and autism spectrum disorder (ASD), inflammatory bowel disease (IBD), or Parkinson’s disease (PD), from inception to July 15,

[0274] 5 2022, August 15, 2022, and May 24, 2023, respectively. The following search terms were used as free-text words only, or as key words; (ASD, Autism Spectrum Disorder, or Autism), (IBD or Inflammatory Bowel Disease), (PD, Parkinson’s Disease, or Parkinson’s), and (gut microbiome, or microbiota, fecal microbiome).

[0275] Studies where the roles of microbiome in ASD, IBD, or PD were researched were read in full to assess their inclusion eligibility. Inclusion criteria include: (a) fecal microbiota samples from a patient with the disorder or disease and or that of a typically developing individual or otherwise healthy control were collected, (b) data and respective metadata were retrievable and interpretable, (c) disorder or disease diagnosis was given by a healthcare professional.

[0276] For studies that met these criteria, a total of 24 ASD cohorts, consisting of 16S rRNA

[0277] 15 and metagenomic (MGX) sequencing data, were included. To further expand the available data, open-source data generated from the American Gut Project (AGP)l was used to cultivate an additional dataset of ASD children and controls. Here, a propensity score algorithm (see below) was used to identify a best-match control subject for each ASD subject. In total, 25 ASD cohorts yielded 2,268 ASD samples and 1,671 control samples of typical developing individuals.

[0278] 20 With the goal of minimizing known technical effects, studies which utilized Roche 454 sequencing, and / or 16S rRNA pyrosequencing were not included. Additionally, thirteen ASD studies met the inclusion criteria, but either did not have publicly available data or the associated metadata was not sufficiently detailed. Authors from these studies were contacted but did not respond to requests for data access nor clarity and thus were unable to be included in these

[0279] 25 analyses.

[0280] Studies utilized in these meta-analyses (e.g., in FIG. 3A) included:

[0281] McDonald D, Hyde E, Debelius JW, Morton JT, Gonzalez A, Ackermann G, Aksenov AA, Behsaz B, Brennan C, Chen Y et al. 2018. American gut: An open platform for citizen science microbiome research. mSystems. 3(3).

[0282] 30 Berding K, Donovan SM. 2019. Dietary patterns impact temporal dynamics of fecal microbiota composition in children with autism spectrum disorder. Front Nutr. 6:193.

[0283] Cao X, Liu K, Liu J, Liu YW, Xu L, Wang H, Zhu Y, Wang P, Li Z, Wen J et al. 2021. Dysbiotic gut microbiota and dysregulation of cytokine profile in children and

[0284] 35 teens with autism spectrum disorder. Eront Neurosci. 15:635925. PCT / US25 / 43182 22 August 2025 (22.08.2025)

[0285] Chen Y, Fang H, Li C, Wu G, Xu T, Yang X, Zhao L, Ke X, Zhang C. 2020. Gut bacteria shared by children and their mothers associate with developmental level and social deficits in autism spectrum disorder. mSphere. 5(6).

[0286] Chen Z, Shi K, Liu X, Dai Y, Liu Y, Zhang L, Du X, Zhu T, Yu J, Fang S et al. 2021.

[0287] 5 Gut microbial profile is associated with the severity of social impairment and iq performance in children with autism spectrum disorder. Front Psychiatry. 12:789864.

[0288] Coretti L, Paparo L, Riccio MP, Amato F, Cuomo M, Natale A, Borrelli L, Corrado G, Comegna M, Buommino E et al. 2018. Gut microbiota features in young children

[0289] 10 with autism spectrum disorders. Front Microbiol. 9:3146.

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[0293] 15 Gilbert JA, Wall DP. 2021. Children with autism and their typically developing siblings differ in amplicon sequence variants and predicted functions of stool- associated microbes. mSystems. 6(2).

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[0295] 20 Psychiatr Res. 129:149-159.

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[0302] 35 Kong X, Liu J, Cetinbas M, Sadreyev R, Koh M, Huang H, Adeseye A, He P, Zhu J, Russell H et al. 2019. New and preliminary evidence on altered oral and gut microbiota in individuals with autism spectrum disorder (asd): Implications for asd diagnosis and subtyping based on microbial biomarkers. Nutrients. 11(9).

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[0306] 45 symptoms by improving the gut microbiota in an open-label study. Front Cell Infect Microbiol . 11:759435.

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[0313] 16S processing pipeline

[0314] For data publicly deposited in the NCBI Sequence Read Archive (SRA), sample metadata was downloaded from each project using the SRA Run Selector tool (ncbi.nlm.nih.gov / Traces). In cases where data and sample metadata were not deposited through SRA, it was downloaded according to the original manuscripts instructions or provided directly from the original study's authors and processed using identical parameters.

[0315] The processing pipeline first removes primer sequences from a list of commonly utilized primer sequences. Next, all sequences were trimmed to a length of 150 bp. After trimming, sequences were denoised, filtered, and summarized into an Amplicon Sequence Variant (ASV) table. The resulting tables were taxonomically annotated with ASV read counts and samples were filtered out if they had less than 4,000 reads. The resulting abundance tables were used for downstream analysis of potential metabolic pathways associated with ASD.

[0316] Compiling an ASP cohort from the American Gut Project

[0317] 25 The AGP dataset contains samples from >29,000 participants thus representing a diverse dataset to compile targeted cohorts with. All available 16S data and metadata was downloaded from Qiita.ucsd.edu (qiita.ucsd.edu / study / description / 10317). As these samples were part of a citizen-science initiative where samples may have been exposed to variable collection conditions, a bloom-filter was applied (github.com / knightlab-analyses / bloom-analyses) to remove Gammaproteobacteria species known to commonly grow at room temperature30.

[0318] After application of the bloom-filter, ASD samples were selected from fecal samples of subjects self-reported as having been diagnosed as ASD by a physician. Next, a closest-match control cohort was selected based on the metadata of each ASD subject. Propensity score matching was utilized to identify the closest control subject match to each ASD sample31. The

[0319] 35 control samples were required to be exact matches for some specific metadata features (e.g., run PCT / US25 / 43182 22 August 2025 (22.08.2025) date, sample type, and sex) and next selected from having the closest ‘similarity score calculated from other metadata features. Exact matching allowed for the selection of features that needed to be controlled for, such as the technical variability between sequencing runs.

[0320] Correlations to ASP behavioral severity

[0321] Scores from subcategories of the Social Responsiveness Scale, Second Edition (SRS-2) 39, were categorized into different severity ranges as recommended. Mild categorization included SRS T-scores between 60-65, moderate ranged from 66-75, severe was above 75. Scores below 60 are categorized as normal as they fall within normal limits and are not generally associated with ASD. Metabolite abundances were averaged per-subject before analyses.

[0322] Example 2. Chorismate Administration Improves ASD Microbiota

[0323] In this Example, the potential benefits of chorismate were explored in laboratory cultures of gut bacteria. Glyphosate, the active ingredient in the herbicide ROUNDUP™, is a known potent inhibitor of the shikimate pathway, which produces chorismate and influences bacterial growth.

[0324] Bacterial strains used for in vitro growth experiments were Escherichia coli (E. coli) ATCC 25922 and Bacteroides thetaiotaomicron (B. theta) VPI 5482 (ATCC 29741). E. coli was grown in M9 minimal media (IX M9 salts, 2 mM MgSO4, 100 mM CaC12, 0.4% glucose) aerobically at °37 C. B. theta was grown in M9SG minimal media (IX M9 salts, 2 mg / L FeSO4.7H2O, 5 mg / L Hemin, 2.5 mg / L Vitamin KI, 5 mg / L Vitamin B12, 2 mM MgSO4, 100 mM CaC12, 0.25% glucose and 0.5 g / L cysteine) anaerobically in a Coy Labs anaerobic chamber supplemented with a gas mixture containing 5% hydrogen, 5% carbon-dioxide and a nitrogen balance.

[0325] A single isolated bacterial colony (picked from respective minimal media plates) was inoculated in liquid media and grown overnight at 37 °C. The following morning, the bacteria were either diluted at 1:25 in the same media (for E. coli) and grown until mid-exponential phase to an OD600 of 0.2-0.6 or used directly in the case of B. theta. In both the scenarios, exponentially growing E. coli and overnight grown B. theta were normalized to an OD600 = 0.02 in the respective media. Working concentration of ROUNDUP™ (Monsanto, containing 3.71b of glyphosate acid per gallon) or pure glyphosate (N-(phosphonomethyl)glycine, Sigma- Aldrich, Cat number P9556) were prepared in the respective bacterial media. Diluted bacteria were mixed with equal volumes of the working concentrations of the pesticide or pure PCT / US25 / 43182 22 August 2025 (22.08.2025) glyphosate to achieve the required final concentrations. For rescue experiments, either chonsmic acid (Sigma- Aldrich, Cat number Cl 761) or an equimolar mixture of the three aromatic amino acids (AAA) (L-tryptophan (Sigma- Aldrich, Cat number T0254), L-tyrosine (Sigma- Aldrich, Cat number T8566) and L-phenylalanine (Sigma- Aldrich, Cat number P5482)) was added to the bacterial cultures with and without glyphosate. Growth was measured at OD600 at 37°C, kinetically (for aerobically growing E. coli) or at the 24 hr endpoint (for anaerobically growing B. theta) in a BioTek Synergy HTX Multimode plate reader. Each experiment was performed in triplicate and repeated twice.

[0326] As shown in FIGs. 6A-6F, chorismate was found to restore bacterial growth inhibited by either glyphosate or ROUNDUP™ in both E. coli and B. theta, suggesting that chorismate can be absorbed and metabolically utilized by gut microbes. Notably, AAA mixture alone was sufficient to restore the inhibited growth in E. coli, and chorismate rescued growth in both E. coli and B. theta. These data suggest that chorismate supplementation is capable of broadly restoring the bacterial growth of gut bacteria (e.g., in a glyphosate sub-type of ASD), while AAA mixture can restore bacterial growth of certain gut bacteria.

[0327] Example 3. Chorismate Administration Improves ASD Microbiota in Mice

[0328] In this Example, effects of chorismate administration on wildtype mouse microbiota was assessed. Chorismate was administered to 8-week-old C57B1 / 6 mice either in the drinking water (chorismate made fresh daily to prevent degradation) or via oral gavage (250 pL) once a day for 6 days (e.g., as shown in FIG. 7A). For each administration route, vehicle-administered groups were compared against 3 doses of chorismate (low, medium, and high). Drinking water cohort: high (0.111 mg / ml), medium (0.011 mg / ml), and low (0.001 mg / ml). Oral gavage cohort: high (1.766 mg / ml), medium (0.176 mg / ml), and low (0.017 mg / ml). Animal health was monitored daily for signs of sickness, discomfort, lethargy, piloerection, and excessive changes in body weight. Animal experiments complied with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals.

[0329] Mice were sacrificed at the conclusion of behavioral testing, and fecal content of the intestinal tract was flash frozen for subsequent analysis. Fecal samples were processed for sequencing and 16s rRNA libraries were prepared and processed as described in Example 1. For mouse fecal samples, shotgun metagenomic DNA libraries were prepared using the Nextera XT DNA Library Preparation Kit (Illumina), with two positive (in-house metagenomic standard and ZymoBiomics community standard) and one negative process control per plate. Libraries were PCT / US25 / 43182 22 August 2025 (22.08.2025) quantified using BioAnalyzer followed by qPCR. Libraries were sequenced to a coverage depth of ~3GB on the Illumina NovaSeq platform 2x 150 bp.

[0330] To identify metabolites associated with chorismate treatment, samples were divided into two groups depending on if the sample originated from mice exposed to chorismate or not, and rank sum test and fold-change statistics were calculated as previously described. Metabolites were ranked for association with chorismate-treatment by P-value, with the abundance of topranked metabolites visualized by seaborn (vO.11.2) pointplot with 95% confidence intervals shown. Animals administered chorismate via gavage and drinking water were analyzed separately.

[0331] To compare the metabolites associated with chorismate administration to ASD, subject- averaged human fecal metabolite abundances was compared between ASD and control individuals via rank sum test. Metabolites with significant ASD association (P<0.05) were examined for additional association to gavage- and water-administration of chorismate in mice. Metabolites were prioritized first by being associated with all three tests (ASD-, gavage-, and water-associated), and next by the absolute value of (ASD / control) fold-change among ASD- associated compounds.

[0332] Chorismate treatment led to significant enrichment of chorismate-derived metabolites in both gavage and drinking-water treated mice, with the largest increase in Gentisic acid, L- tryptophan, and L-tyrosine, and a reduction in Paxilline and 3 -Dehydro shikimic acid (FIGs. 7B- 7E). These metabolites were compared with those altered in the new human ASD cohort described in Example 1, and an overlap in metabolites that could be beneficial for ASD was observed, including hypoxanthine, xanthine, L-lysine, L-glutamic acid, L-tryptophan, and Riboflavin (FIG. 7F).

[0333] Example 4. Chorismate Improves ASD-like Behavior in Mice

[0334] In this Example, effects of chorismate treatment on behavior in three ASD-like animal models was assessed. Three established ASD mouse models were used: glyphosate exposure during pregnancy, the valproic acid (VPA) model, and the genetically altered BTBR mouse strain.

[0335] Mouse Models

[0336] Male C57B1 / 6 mice were used for wild-type control and drug-induced ASD models. BTBR mice were obtained from the Jackson Laboratories (jax.org / strain / 002282). Mice were PCT / US25 / 43182 22 August 2025 (22.08.2025) housed in a temperature- and humidity-controlled room with a 12 h hght / dark cycle, and fed ad libitum. Valproic acid-induced ASD model mice were obtained by administering to pregnant C57B1 / 6 females a single intraperitoneal injection of valproic acid (VPA) at a dose of 700 mg / kg, administered in a volume of 500 pL, on Gestational Day 12.5. Male pups were weaned at 3 weeks of age (P21) and used in the experiments described herein. Glyphosate-induced ASD model ice were obtained by providing pregnant C57B1 / 6 females with either regular drinking water or water infused with glyphosate at a dose of 175mg / kg (-0.1%) in the initial cohort or 350 mg / kg (-0.2%) in a validation cohort from Embryonic Day 5 (E5) until Postnatal Day 21 (P21), spanning a total duration of 37 days. Male pups were weaned at 3 weeks of age (P21) and used in the experiments described herein.

[0337] Animals were split into treatment groups (vehicle (control), chorismate, or shikimate) and treated from P21 to P56 (e.g., as shown in FIG. 8A). Mice received treatments in drinking water or via oral gavage at a concentration of 0.35 mg / mL, administered in a volume of 250 p L per gavage, after weaning until they reached the age of P56. At P56, mice underwent behavioral testing in a 3-chamber sociability test, elevated plus maze, marble burying test, and reciprocal social interaction test.

[0338] Three-chamber sociability test

[0339] To test sociability in mice, a non-transparent plexiglass arena with the base measuring 60 x 40 cm, featuring two partitions creating left and right chambers separated by a central chamber (each chamber is 20 x 40 cm). On P56, the mouse was allowed to habituate for 5 min in the arena with two empty wire cages positioned in the left and right chambers. In the subsequent 10- minute session, an unfamiliar mouse was introduced into one of the wire cages. The placement of the unfamiliar mouse was randomized in a counterbalanced manner. Mouse movements were recorded using an overhead camera and analyzed with Noldus Ethovision software. Time spent by the mouse in each chamber within a 2-cm radius around each wire cage was recorded. Social interaction ratio was calculated from the following equation: social interaction ratio = (time spent at social wire cage) / (time spent at empty wire cage).

[0340] Reciprocal social interaction test

[0341] The subject mouse underwent a 10-minute habituation period in a new mouse cage. Subsequently, an unfamiliar male mouse was introduced to the arena for a duration of 5 minutes. To mitigate the potential for mutual aggression, a male juvenile aged between 4 and 5 weeks PCT / US25 / 43182 22 August 2025 (22.08.2025) was selected and utilized as the unfamiliar mouse. Throughout this interaction period, a deeplearning based framework for multi-animal pose tracking was used to capture various types of social interactions between the animals, such as nose-to-nose contact. Distances between body points of the subject mouse and unfamiliar mouse were calculated and used for subsequent analysis.

[0342] Elevated plus maze

[0343] The elevated plus maze apparatus (EPM) consisted of two open arms, two closed arms, and a central area. Mice were individually introduced into the central area and allowed to freely explore the maze for 5 minutes. Time spent in each arm was determined using the Noldus Ethovision software. The data were reported as the percentage of time spent in the open arms.

[0344] Marble burying test

[0345] The subject mouse was introduced into a clean cage containing 3-4 cm of fresh, autoclaved wood chip bedding. Following a 10-minute habituation period, the mice were temporarily transferred to a secondary cage while the bedding was leveled, and 20 glass marbles (arranged in a 4 x 5 grid) were placed on top of the bedding. Subsequently, each mouse is returned to the cage for an additional 10 minutes. The number of marbles buried to a depth covering 50% of their surface area was then meticulously recorded and photographed for future reference. To eliminate any residual scent from previous mice, the bedding was replaced for each subsequent mouse, and the marbles were thoroughly cleaned by soaking them in 70% ethanol and subsequently dried within the bedding material between successive tests. The data were transformed using the following formula where higher values indicate reduced repetitive behavior: (total marbles - marbles buried) / total marbles.

[0346] Results

[0347] All models exhibited significant social deficits in the three-chamber sociability test, mirroring a core ASD symptom (P<0.05, FIG. 8B). Notably, chorismate treatment significantly increased sociability across all three animal models, indicating robust benefits on social behavior (Overall treatment effect P=0.001, FIG. 8B). Additional ASD-related symptoms, including repetitive behaviors, communication challenges, and anxiety, were also assessed. In the elevated plus maze (EPM), only VPA-treated mice displayed increased anxiety, which was significantly reduced by chorismate treatment (P=le-4, FIG. 8C). All models showed increased repetitive behaviors in the marble-burying test, and chorismate treatment exhibited a trend toward PCT / US25 / 43182 22 August 2025 (22.08.2025) reduction (P=0.057; Fig. 4d, FIG. 8D). No significant effects were observed in ultrasonic vocalization tests for communication difficulties (data not shown). Total distance traveled in three-chamber sociability test arena and EPM, and total time spent in closed or open arms in the EPM were also assessed to confirm increased sociability was not due to increased movement

[0348] 5 (data not shown).

[0349] As a secondary measure of sociability, reciprocal social interactions were recorded in an open-cage setting containing a stranger mouse. Both BTBR and VPA-treated mice displayed fewer nose-to-nose interactions, which was significantly improved by chorismate (BTBR P=0.031, VPA P=0.014; FIG. 8E). Of interest, administration of shikimate, a further upstream

[0350] 10 precursor to chorismate, did not replicate chorismate’ s behavioral benefits, indicating the unique impact of chorismate on ASD-like behaviors (FIGs. 8B-8E).

[0351] Overall, these findings indicate that chorismate and its derivatives are depleted in ASD, impacting pathways crucial for neurodevelopment, including aromatic amino acids and folate synthesis. Moreover, chorismate supplementation in ASD-like mice improves sociability, reduces anxiety, and modulates ASD-relevant metabolites. These Examples not only clarify the complex role of the microbiome in ASD but also point to chorismate as a potential biomarker and therapeutic target, paving the way for novel metabolic interventions. Finally, these finding suggest that glyphosate is a potential disruptor of chorismate production within the ASD

[0352] 20 microbiome, e.g., during prenatal and early-life glyphosate exposure.

Claims

PCT / US25 / 43182 22 August 2025 (22.08.2025)CLAIMSWhat is claimed is:

1. A composition comprising a predetermined amount of at least one chorismate metabolite and a predetermined amount of an additional active ingredient.

2. The composition of claim 1, wherein the at least one chorismate metabolite is Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, choline, folinic acid (5-MFHP), or a combination thereof.

3. The composition of claim 1 or 2, comprising 2 or more chorismate metabolites.

4. The composition of any one of claims 1 to 3, comprising 3 or more chorismate metabolites.

5. The composition of any one of claims 1 to 4, comprising 4 or more chorismate metabolites.

6. The composition of any one of claims 1 to 5, comprising 5 or more chorismate metabolites.

7. The composition of any one of claims 1 to 6, comprising Vitamin K2, L-tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP).

8. The composition of claim 7, wherein the Vitamin K2, L-tryptophan, 5-Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, and folinic acid (5-MFHP) are present in a predetermined molar ratio.

9. The composition of any one of claims 1 to 8, wherein the additional therapeutic agent comprises an amino acid.

10. The composition of claim 9, wherein the amino acid is L-camosine.PCT / US25 / 43182 22 August 2025 (22.08.2025)11. The composition of any one of claims 1 to 10, wherein the additional therapeutic agent comprises riboflavin.

12. The composition of any one of claims 1 to 11, wherein the additional therapeutic agent comprises Vitamin B2.

13. The composition of any one of claims 1 to 12, wherein the additional therapeutic agent comprises Vitamin D3.

14. The composition of any one of claims 1 to 13, further comprising a carrier.

15. The composition of claim 14, wherein the carrier comprises a polymer that is not absorbed in a gastrointestinal tract.

16. The composition of claim 14 or 15, wherein the carrier comprises polyvinylpyrrolidone.

17. The composition of any one of claims 14 to 16, wherein the chorismate metabolite and additional therapeutic agent are loaded into the carrier.

18. The composition of any one of claims 14 to 17, further comprising a substance that facilitates a targeted delivery of the chorismate metabolite, the additional therapeutic agent, and the carrier to an intestinal location.

19. The composition of claim 18, wherein the substance comprises a first material that dissolves at a pH between about 6.0 and about pH 7.6.

20. The composition of claim 19, wherein the first material dissolves at a pH 7.5.

21. The composition of any one of claims 18 to 20, wherein the substance comprises a second material that is susceptible to degradation by a microbial organism.

22. The composition of claim 21, wherein the second material is susceptible to degradation by a microbial organism present in a large intestine of a subject.PCT / US25 / 43182 22 August 2025 (22.08.2025)23. The composition of claim 21 or 22, wherein the second material is susceptible to degradation by a microbial organism present in a colon of a subject.

24. The composition of claim 18, wherein the substance comprises a first material that dissolves at a pH between about pH 6.0 and about pH 7.6 and a second material that is susceptible to degradation by a microbial organism present in a large intestine of a subject.

25. The composition of claim 18, wherein the substance comprises a scaffold.

26. The composition of claim 25, wherein the scaffold comprises a first material that dissolves at a pH between about 6.0 and about pH 7.

6. and a second material of the substance comprises a second material that is susceptible to degradation by a microbial organism.

27. The composition of any one of claims 18 to 26, wherein the substance comprises one or more layers.

28. The composition of claim 27, wherein a first layer of the substance comprises a first material that dissolves at a pH between about 6.0 and about pH 7.

6. and a second layer of the substance comprises a second material that is susceptible to degradation by a microbial organism.

29. The composition of any one of claims 1 to 28, wherein the composition is a nutraceutical composition.

30. The composition of any one of claims 1 to 28, wherein the composition is a pharmaceutical composition.

31. A composition comprising: a core comprising a predetermined amount of at least one chorismate metabolite; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.PCT / US25 / 43182 22 August 2025 (22.08.2025)32. A composition comprising: a core comprising a predetermined amount of at least one chorismate metabolite and a predetermined amount additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

33. A composition comprising: a core comprising a predetermined amount of two or more chorismate metabolites; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

34. A composition, comprising: a core comprising: a predetermined amount of L-camosine; and a predetermined amount of Vitamin K2, L- tryptophan, 5-Hydroxytryptohan (5- HTP), L-tyrosine, L-phenylalanine, choline, folinic acid (5-MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

35. A composition, comprising: a core comprising: a predetermined amount of riboflavin; and a predetermined amount of Vitamin K2, L- tryptophan, 5-Hydroxytryptohan (5- HTP), L-tyrosine, L-phenylalanine, choline, folinic acid (5-MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.PCT / US25 / 43182 22 August 2025 (22.08.2025)36. A composition, comprising: a core comprising: a predetermined amount of Vitamin B2; and a predetermined amount of Vitamin K2, L- tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, choline, folinic acid (5- MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

37. A composition, comprising: a core comprising: a predetermined amount of Vitamin D3; and a predetermined amount of Vitamin K2, L- tryptophan, 5- Hydroxytryptohan (5-HTP), L-tyrosine, L-phenylalanine, choline, folinic acid (5- MFHP), or a combination thereof; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the pharmaceutical composition is administered.

38. A composition, comprising a predetermined amount of two or more metabolites of a chorismate pathway.

39. The composition of any one of claims 1 to 38, for use in a method comprising providing the composition to a subject.

40. The use of claim 39, wherein the subject has or is at risk of developing autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), epilepsy, schizophrenia, a sleep disorder, an anxiety disorder, depression, or an eating disorder.

41. The use of claim 39 or 40, wherein the subject has or is at risk of developing ASD.PCT / US25 / 43182 22 August 2025 (22.08.2025)42. The use of any one of claims 39 to 41, wherein the subject has been determined to have an altered level of one or more chorismate metabolites relative to a level of the same chorismate metabolites in a neurotypical individual.

43. The use of claim 42, wherein the altered level is determined from a sample of the subject.

44. The use of claim 43, wherein the sample of the subject is a fecal sample.

45. A method of treating a subject having or at risk of developing autism spectrum disorder, the method comprising: providing to the subject a composition, the composition comprising: a core comprising: a predetermined amount of at least one chorismate metabolite and a predetermined amount of an additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is provided.

46. The method of claim 45, further comprising a step of determining that the subject has an altered intestinal level of one or more chorismate metabolites relative to a neurotypical individual, wherein the determining occurs prior to the providing.

47. A method of treating a subject determined to have an altered intestinal level of one or more chorismate metabolites relative to a healthy individual, the method comprising providing to the subject a composition, the composition comprising: a core comprising: a predetermined amount of at least one chorismate metabolite and an additional therapeutic agent; and a controlled release coating applied to an exterior surface of the core, wherein the controlled release coating is configured to release the core in a large intestine and / or small intestine of a subject to whom the composition is provided.

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