Methods and compositions for producing phytonutrients in microbiome

Abstract

The present disclosure relates to methods and compositions for the production of phytonutrients in microbiome. Methods are disclosed that can be used to provide phytonutrients to a subject via mediating the microbiome of the subject. The methods include administering to a subject a plant functional composition to alter the state of a phytonutrient producer in the subject. The method may also include identifying a phytonutrient producer status of the subject by evaluating a level of at least one of a preselected phytonutrient and a preselected phytonutrient precursor compound in the subject. Also disclosed are plant functional compositions useful in the methods and comprising a phytonutrient precursor compound and an active agent. The active agent comprises probiotics and / or prebiotics and is adapted to mediate the production of the preselected phytonutrients in the gastrointestinal tract of the subject, thereby altering the phytonutrient producer status of the subject.

Description

[0001] This application is a divisional application of the invention patent filed on September 23, 2020, with application number 202080066991.7 (PCT / US2020 / 052128) and entitled "Method and Composition for Producing Phytonutrients in a Microbiome".

[0002] Cross-reference to related applications This application claims priority and all advantages of U.S. Provisional Application No. 62 / 904,826, filed September 24, 2019, and U.S. Patent Application No. 17 / 028,490, filed September 22, 2020, the contents of which are each incorporated herein by reference. Technical Field

[0003] This invention relates to methods for improving microbial metabolism, and more particularly, to methods and compositions for providing phytonutrients to subjects. Background Technology

[0004] Phytonutrients are plant-derived compounds associated with a variety of health benefits in mammals, such as humans, including antioxidant activity, improved cardiovascular health, anti-inflammatory activity, anti-aging properties, and neurological benefits. For example, polyphenolic phytonutrients (e.g., flavonoids) are positively associated with neurological benefits such as improved memory and learning behavior in adults. Despite their potential benefits, phytonutrients are generally not used in food supplements because typical phytonutrients, when added to food / nutritional products, can impart undesirable color and / or taste to existing products. Therefore, many phytonutrients are provided to mammals in the form of nutritional supplements, which are often concentrated sources of nutrients (e.g., phytonutrients) given to provide nutritional and / or physiological functions. However, some phytonutrients are not naturally present in their biologically active form (i.e., at complete or adequate levels) but rather in their precursor form (e.g., as phytonutrient precursor compounds). Consequently, many phytonutrient-based nutritional supplements are ineffective or inefficient because such phytonutrient precursor compounds are not adequately converted into their bioactive form, which is beneficial to mammalian health, before being excreted by the mammal. Summary of the Invention

[0005] A method is provided to alter the phytonutrient producer status of a subject. The method can be used to mediate the subject's microbial metabolism, for example, to maintain or improve the subject's health or well-being. The method may include identifying the subject's phytonutrient producer status, for example, by assessing the level of at least one of a preselected phytonutrient and a preselected phytonutrient precursor compound within the subject. The method includes administering a plant-based functional composition to the subject to alter the subject's phytonutrient producer status. The plant-based functional composition comprises a phytonutrient precursor compound and an active agent. The active agent comprises at least one of a probiotic and a prebiotic and is adapted to mediate the production of the preselected phytonutrient in the subject's gastrointestinal tract.

[0006] In some implementations, the method includes identifying one or more probiotics, prebiotics, and / or phytonutrient precursor compounds to alter the phytonutrient producer status of the subject.

[0007] In some embodiments, the method includes formulating the plant functional composition to include identified probiotics, prebiotics, and / or phytonutrient precursor compounds before administering the plant functional composition to the subject.

[0008] Plant functional compositions suitable for the methods are also provided. Specifically, the plant functional compositions comprise phytonutrient precursor compounds suitable for conversion into phytonutrients via microbial metabolism or otherwise used in the production of phytonutrients. The plant functional compositions further comprise an active agent suitable for mediating the production of a preselected phytonutrient from the phytonutrient precursor compounds in the gastrointestinal tract of a subject. The active agent comprises probiotics and / or prebiotics.

[0009] These and other objects, advantages and features of the present invention will be more fully understood and appreciated by referring to the description of the current embodiments.

[0010] Before explaining the embodiments of the present invention in detail, it should be understood that the present invention is not limited to the details of operation or the construction and arrangement of the steps or components set forth in the following description. It should be understood that the wording and terminology used herein are for descriptive purposes only and should not be considered limiting. The use of “comprising” and “including” and variations thereof means including the items listed thereafter and their equivalents, as well as other items and their equivalents. Furthermore, enumeration may be used in the description of various embodiments. Unless expressly stated otherwise, the use of enumeration should not be construed as limiting the invention to any particular order or number of components. Nor should the use of enumeration be construed as excluding from the scope of the invention any additional steps or components that may be combined with or incorporated into the enumerated steps or components. Detailed Implementation

[0011] The methods disclosed herein can be used to provide phytonutrients to subjects. Typically, the methods utilize function-driven metagenomics to identify potential treatments within complex microbial communities and to utilize these treatments to benefit the subject. More specifically, as will be understood from the description herein, the methods can be used to improve the condition of subjects by providing them with phytonutrients metabolized by their microorganisms, for example, by administering a functional plant composition to the subject to mediate the subject's microbial metabolism, thereby providing the subject with adequate phytonutrients.

[0012] Plant compounds are chemical entities found in or derived from plants. Plant compounds vary widely and can be macromolecules, polymers, low molecular weight molecules, small molecules, etc. Many plant compounds are biologically inactive for certain biological processes, for example, because they are indigestible, have low bioavailability, and / or are otherwise resistant or inert to specific biological targets. However, some such plant compounds can be converted into forms with increased biological activity against one or more biological targets via microbial metabolism (e.g., through the subject's microbiome). In such cases, the parent plant compound with lower biological activity (i.e., for at least one biological target) can be referred to as a "phytonutrient precursor compound," and its biologically active metabolite is referred to as a "phytonutrient." While the term "phytonutrient" is conventionally used synonymously with "plant compound," for clarity, the term "phytonutrient precursor compound" herein refers to any plant compound, whether naturally occurring or derived from naturally occurring compositions, that can be converted into a biologically active compound via microbial metabolism. Furthermore, such biologically active compounds (i.e., those derived from the microbial metabolism of phytonutrient precursor compounds) are referred to herein as "phytonutrients."

[0013] As used herein, the terms “microbiome,” “microbiota,” and “microbial habitat” are used interchangeably and refer to the microorganisms within and / or on the body of a host animal (e.g., a mammal, such as a human). A microbiome can collectively comprise symbiotic, commensal, and / or pathogenic microorganisms known to have profound effects on the health of the host. A microbiome can be present on or within many (if not most) parts of the host. Therefore, specific terms can be used to refer to a localized microbiome, such as within or on a specific part of the host. For example, the term “gut microbiota” refers to the microorganisms (i.e., the microbiota) that typically survive in the gastrointestinal (GI) tract of an animal host. The gut microbiota present in typical animals is highly diverse and includes pathogenic, benign, and beneficial genera of microorganisms. In typical healthy humans, the gut microbiota comprises beneficial bacteria (e.g., Lactobacillus and Bifidobacterium) and non-beneficial gut bacteria (e.g., Bacteroides, Coliforms, Clostridium, and sulfate-reducing bacteria). For example, the human colon contains a localized microbiome with the highest degree of biodiversity in the human body, with an estimated bacterial density of approximately 102. 12 Each bacterium / g consists of colonic contents composed of hundreds of individual bacterial species. Therefore, it can be expected that the gut microbiota of a given host subject (e.g., an individual person) will exhibit its own characteristic metabolic profile, as detailed below.

[0014] Therefore, it should be understood that the microbiome of a given host subject will be unique in many respects, but will generally also share many similarities with the microbiome of other hosts in a given population. One such aspect is the ability or inability to metabolize specific phytonutrient precursor compounds into specific phytonutrients. In other words, in a given population, any particular subject may be able to metabolize certain phytonutrient precursor compounds via microbial metabolism, but not others. For example, the phytonutrient equol is formed after the hydrolysis of daidzein glycoside conjugates from soybean and the methoxylated isoflavone monganin or its glycoside conjugates found in clover (i.e., phytonutrient precursor compounds). Once formed, equol appears to be metabolically inert, undergoing no further biotransformation, no phase II metabolism, or a small degree of additional hydroxylation in the liver. Following the initial discovery of equol in urine after ingestion of soy-containing foods, it is estimated from observed results that 50–70% of the adult population does not excrete equol in urine, even with daily consumption of soy-containing foods. Furthermore, even when given pure isoflavone compounds (i.e., without the influence of the food matrix), many people do not convert daidzein into equol. This phenomenon leads to the terms "equol producer" or "non-equol producer" (or "weak equol producer") to describe these two distinct groups. As those skilled in the art will understand, empirical values ​​can be designated as "cutoff" values ​​to distinguish these categories. For example, subjects with plasma equol concentrations below 10 ng / mL (40 nmol / L) can be classified as "non-equol producers," while subjects with equol levels above 10 ng / mL (40 nmol / L) can therefore be classified as "equol producers." Such classification can also be derived from urinary levels; for example, when the excreted equol concentration is greater than 1000 nmol / L, the subject is classified as an "equol producer."

[0015] It should be understood that certain phytonutrient precursor compounds (i.e., dietary plant compounds) present in large quantities in food are initially absorbed in the ileum of the subject, subsequently excreted as conjugates in bile, and ultimately pass through the small intestine before reaching the subject's colon. However, it is now known that a portion of non-absorbed / unabsorbed phytonutrient precursor compounds can directly reach the subject's colon after passing through the gastrointestinal tract, and are thus subjected to various microbial metabolic processes (e.g., fermentation, oxidation, deconjugation, etc.) by the gut microbiota to provide a wide range of phytonutrients as low-molecular-weight metabolites that can be absorbed by the host. Therefore, the phenomena described above regarding equol can be generalized and described based on any specific phytonutrient produced via microbial metabolism, classifying subjects as "phytonutrient producers," "non-phytonutrient producers," "weak phytonutrient producers," etc.

[0016] In some embodiments, the method includes identifying or assessing the subject's phytonutrient producer status. As will be understood from the description herein, the specific techniques and / or individual methods used for assessment and / or identification are not particularly limited and may be or include any suitable in vitro, in vivo, empirical, qualitative, and / or quantitative techniques adapted to evaluate the presence and / or level (e.g., concentration) of an active agent of a particular phytonutrient, its metabolite or metabolic precursor (e.g., the corresponding phytonutrient precursor compound), or any of the aforementioned or other quantifiable markers (collectively, "biomarkers") capable of producing phytonutrient producer status in the subject (e.g., directly, via a sample, via a representative sample, etc.). However, it should also be understood that in some embodiments, the individual subject's phytonutrient producer status does not need to be directly identified or assessed prior to administration of the phytofunctional composition to the subject. Instead, the phytofunctional composition may be formulated based on an assessment of common phytonutrient producer statuses (e.g., globally, or within a specific population) and administered to the subject based on its association with those statuses. Therefore, while the method described can be used to provide personalized preventive effects to specific subjects, it can also be used based on the ability to provide preventive effects to a portion of a given population (e.g., as a general supplement to potential metabolic support, as further detailed below).

[0017] Subjects are not restricted and can be any organism with a microbiome. However, subjects are typically animals, such as mammals (i.e., vertebrates of the class Mammalia, such as dogs, cats, goats, sheep, pigs, cattle, horses, donkeys, camels, etc.). Additional mammals specifically anticipated herein include semi-domesticated mammals and conventionally domesticated mammals. Of course, the term mammal also includes humans (which may be referred to as "human" and / or "one or more humans"). When describing humans, the term "adult" is generally used herein to refer to a person who has reached sexual maturity. Conversely, the terms "child" and "adolescent" are used herein to refer to a person who has not yet reached sexual maturity. Generally, the term "child" refers to a human subject between birth and approximately 10 years of age (i.e., childhood), and the term "adolescent" refers to a human subject older than approximately 10 years of age who has not yet completed puberty. Of course, the terms child, adolescent, adult, and infant are all included in the term human, which itself is a subclass of mammals, and a subclass of animals as defined herein.

[0018] Any evaluation technique can be used, such as urine analysis, stool analysis, plasma analysis, tissue analysis, saliva analysis, etc., or combinations thereof. Furthermore, such techniques can be range-specific (i.e., tailored to one or more specific biomarkers) or systemic, such as those involving multi-omics techniques suitable for identifying biomarkers in one or more tissues of other biological materials of the subject (e.g., blood, urine, sweat, saliva, fecal matter, etc.). Moreover, such evaluations can be of a direct or indirect nature, such as those assessing specific biomarkers in a sample (i.e., direct evaluations) and those assessing the characteristics or properties of biomarkers indicating their association with the status of phytonutrient producers. For example, direct metabolomics, proteomics, and / or genomic analysis can also be used. Additionally, physical indicators (i.e., rather than biological indicators) can be used, or optionally. For example, the Bristol stool score, an indicator of constipation (e.g., harder stools), has been shown to be associated with higher Shannon diversity, an alpha-diversity measure summarizing taxonomic richness and evenness, which is increasingly reported in the gut microbiome literature and can be used as a marker of microbiome health. Therefore, physical indicators (e.g., hard or soft stool), Bristol scores or other descriptive, qualitative and / or quantitative measurements used to describe such stool, indicators associated with such measurements, or even population data (e.g., obtained through sample collection, surveys, etc.) indicating the presence or likelihood of such indicators, measurements or physical indicators can be used to identify or evaluate a subject's phytonutrient producer status.

[0019] Therefore, those skilled in the art will understand that the evaluation of a subject's phytonutrient producer status can include conducting trials, studies, and / or model-based experiments, such as those described in more detail below. In some embodiments, assessing a subject's phytonutrient producer status includes performing high-throughput analysis or screening. In these or other embodiments, assessing a subject's phytonutrient producer status includes utilizing microarrays representing the microbiome, such as microarrays representing the gut or colon microbiome. Such microarrays can be modified from those known in the art, which typically utilize commercially available materials.

[0020] For example, in some embodiments, the method includes fermentation by culturing a microbiome sample obtained from a subject, the microbiome sample being incubated with phytonutrient precursor compounds. Fermentation can be carried out using a culture model, such as an in vitro gut model (i.e., a model representing the human colonic microbiome that simulates microbial processes in the human large intestine). In some embodiments, fecal samples are used for batch fermentation. As those skilled in the art will understand, such determinations provide an efficient comparison of the microbial fermentation processes of different human microbiotas using metabolite analysis methods under conditions simulating those present in the distal colon. Regardless of the specific fermentation technique used, the evaluation typically includes monitoring the presence and, optionally, the amount of phytonutrients (e.g., as decomposition products) produced during fermentation. Such monitoring can be carried out by various metabolite analysis techniques known in the art, such as by nuclear magnetic resonance (NMR)-based metabolite analysis, gas chromatography-mass spectrometry (GC-MS)-based analysis, and combinations thereof.

[0021] In some implementations, assessing a subject's phytonutrient producer status is further defined as evaluating the functional capacity of the subject's gut microbiota. Specifically, the beneficial effects believed to be obtained through the ingestion of certain foods depend on the bioconversion of plant compounds into bioactive metabolites by gut bacteria, i.e., the provision of certain phytonutrients from phytonutrient precursor compounds. It should be understood that the underlying mechanisms and bacterial species involved in such phytonutrient production have not been fully identified, and studies on the bacterial metabolism of the complex mixture of plant compounds present in the human diet are far less extensive than on single compounds. However, as demonstrated herein, differences in phytonutrient producer status can be attributed to differences in the metabolic potential of the endogenous microbiota in a given subject.

[0022] In some embodiments, assessing a subject's phytonutrient producer status involves quantifying the amount of a particular phytonutrient present in the subject, typically expressed as a relative concentration (e.g., blood concentration level, urine concentration level, etc.). It should be understood that the excretion of a particular phytonutrient can be highly variable in individuals, and therefore small or large boundaries may exist between producers and non-producers of a given phytonutrient. Therefore, in some embodiments, assessing a subject's phytonutrient producer status involves comparing the subject's bioconcentration and / or excretion of the phytonutrient with proportionate measurements obtained from other subjects. Such proportionate measurements can be obtained directly or indirectly, for example, via population sampling, surveys, averaging, etc. In some embodiments, the method includes determining empirical cutoff values ​​for the bioconcentration and / or excretion of any particular phytonutrient or multiple phytonutrients within a group, to distinguish the category of those phytonutrient production statuses (e.g., producers relative to non-producers). In such an implementation, comparing a subject’s bioconcentration and / or excretion of phytonutrients with commensurate measurements obtained from other subjects may include comparing a subject’s phytonutrient content with a cutoff value, or otherwise by comparing a subject’s phytonutrient content with a cutoff value, thereby classifying the subject as a producer or non-producer of a given phytonutrient.

[0023] The specific phytonutrient being assessed is not limited. Rather, this method can be used for any phytonutrient produced via in vivo microbial metabolism of phytonutrient precursor compounds in a subject. Furthermore, any quantity of phytonutrients and / or phytonutrient precursor compounds can be assessed, administered, or otherwise utilized in this method. Certain general examples of phytonutrients include dietary carbohydrates (e.g., resistant starch), lipids (e.g., ω3, ω6, etc.), proteins (e.g., whole, isolated, hydrolyzed, etc., from soybeans, whey, rice, peas, etc.), phenylpropanoids (i.e., aromatic compounds containing a phenylpropane moiety), pteridine, benzopyrans, benzene ring compounds, lignans, neolignans, etc., and their derivatives, modifications, and combinations thereof. For example, such phytonutrients can include proteins, peptides, complex amino acids (e.g., those found in plant- or animal-based protein isolates from whey, eggs, soybeans, rice, wheat, beans, algae, fungi, peas, potatoes, fruits, buckwheat, corn, etc.), branched-chain amino acids, medium- and short-chain fatty acids (e.g., hexanoic acid, caprylic acid, capric acid, lauric acid, isovaleric acid, valeric acid, isobutyric acid, butyric acid, propionic acid, acetic acid, formic acid, etc.), hydroxy acids (e.g., lactic acid, etc.), as well as their derivatives, modifications, and combinations thereof. Some examples of phytonutrients include phenylpropionic acid, flavonoids (i.e., compounds containing a 2-phenylchromene moiety), isoflavones (i.e., compounds containing a 3-phenylchromene-4-one moiety or a moiety derived therefrom), hydroxyisoflavones (i.e., hydroxyfunctional isoflavones), isoflavone-2-ene (i.e., compounds containing a 3-phenylchromene moiety having a chromene C2-C3 olefin), flavanones (i.e., compounds containing a flavanone-3-one moiety, including those containing a 2-phenyl-3,4-dihydro-2H-1-benzopyran carrying a C3 ketone), and isoflavones (i.e., compounds containing...). Polycyclic compounds containing the C4-keto-2-isoflavone moiety, flavanes (i.e., compounds containing the 2-phenyl-3,4-dihydro-2H-1-benzopyran moiety), coumarins (i.e., compounds containing the 1-benzopyran-2-one moiety), isocumarins (i.e., C1-ketoisochromanols), pterin (i.e., polycyclic aromatic compounds containing the pterin moiety), chromones (i.e., compounds containing the benzopyran-4-one moiety), phenols (e.g., hydroquinones, such as catechols), dibenzylbutane lignans, dibenzylbutane glycol lignans, etc., and their derivatives, modifications, and combinations thereof.Specific examples of phytonutrients may include: 2-(4-hydroxyphenyl)propionate; 2,3-dehydroestradiol; 2,4,6-trihydroxybenzaldehyde; 2,4,6-trihydroxybenzoic acid; 3-(3,4-dihydroxyphenyl)acetic acid; 3-(3,4-dihydroxyphenyl)propionate; 3-(3-hydroxyphenyl)propionic acid; 3-(4-hydroxyphenyl)propionate; 3,4-dihydroxybenzoic acid; 3,4-dihydroxybenzaldehyde; 3,4-dihydroxyphenylacetaldehyde; 3,4-dihydroxyphenylacetate; 3,4-dihydroxyphenylacetate; 3,4-dihydroxyphenylenolpyruvate; 3,4-dihydroxyphenylpyruvate; 4-hydroxyphenylacetate; 5-(3',4'-dihydroxyphenyl)-γ-valerolactone; 5-(3 ',5'-dihydroxyphenyl)-γ-valerol; 6'-hydroxy-O-demethylanthostigmine; acetate; α-2',3,4,4',6'-hexahydroxydihydrochalcone; alphitonin; butyrate; daidzein; dihydrodaidzein; enterodiol; enterolone; equol (e.g., (S)-equol); sagein; ethanol; formate; genistein; glucose; hemooeriodictyol; hesperidin; lactate; O-demethylanthostigmine; phenyl acetate; phloroglucinol; protocatechuic acid; quercetin; sulfurophane; taxine; tetrahydrodaidzein; urolithin A (e.g., 3,8-dihydroxybenzo[c]chromene-6-one), etc., and their derivatives, modifiers and combinations thereof. However, it should be understood that other phytonutrients (including those derived from the phytonutrient precursor compounds described herein) may be evaluated as substitutes for any of the phytonutrients described above, or the other phytonutrients may be evaluated in addition to any of the phytonutrients described above.

[0024] In some implementations, assessing a subject's phytonutrient producer status includes determining the presence and / or amount of phytonutrients present in or secreted by the subject, wherein the phytonutrients include: protocatechuic acid; 3-(3,4-dihydroxyphenyl)-acetic acid; 3-(3-hydroxyphenyl)-propionic acid; 3,4-dihydroxybenzoic acid; 2,4,6-trihydroxybenzaldehyde; 2,4,6-trihydroxybenzoic acid; sennaol; hesperidin; hesperidin; hesperidin; parargonidin-3-O-glucoside; urolithin A. (e.g., 3,8-dihydroxybenzo[c]chromene-6-one); (S)-estradiol; O-demethylangolasterone; enterodiol; enterolactone; sulforaphane; 5-(3′,4′-dihydroxyphenyl)-γ-valerol; 5-(3′,5′-dihydroxyphenyl)-γ-valerol; dihydrocaffeic acid; isoflavonic acid; 4-hydroxyphenylacetic acid; dihydroferruvic acid, ferulic acid; resorcinol; phloroglucinol; 2,4-dihydroxyphenylacetic acid; 4-hydroxybenzoic acid; phloroglucinic acid; phorbolic acid; phorbolic acid; hydrogenated cinnamic acid; protocatechuic acid; and / or hippuric acid.

[0025] The method includes administering a composition to a subject to improve the subject's phytonutrient producer status. Therefore, the method provides a means of overcoming the lack of production of one or more specific phytonutrients in a subject, such as those described herein. As will be understood from the following description, the phytofunctional composition can increase the functional capacity of a subject's natural gut microbiota (e.g., by stimulating the microbes therein), supplement the functional capacity of the subject's gut microbiota (e.g., by providing additional microbial species and / or altering their population ratios), and / or circumvent certain microbial metabolic processes (e.g., by providing phytonutrient precursor compounds that do not require certain microbial-mediated transformations, thereby bypassing certain metabolic requirements). Regardless of the mechanism, administering the phytofunctional composition to a subject generally results in the production of phytonutrients from phytonutrient precursor compounds (e.g., via microbial metabolism). In some embodiments, administering the phytofunctional composition results in an increase in phytonutrient production in non-producers, by an amount greater than 0-1000%, or greater than 0-500%, or greater than 0-200%, or greater than 0-100%, compared to phytonutrient production in non-producers who have not been given the phytofunctional composition. In these or other embodiments, administration of the plant functional composition results in an increase in the production of phytonutrients in the subject, in an amount greater than 0-5000, or greater than 0-2500, or greater than 0-1000, or greater than 0-750, or greater than 0-500, or greater than 0-250, or greater than 0-200, or greater than 0-150, or greater than 0-100, or greater than 0-75, or greater than 0-50, or greater than 0-40, or greater than 0-30, or greater than 0-25, or greater than 0-20, or greater than 0-15, or greater than 0-10, or greater than 0-5 nmol / L. In such embodiments, the specific amount of phytonutrient produced can vary, for example, based on the amount of plant functional composition administered, the subject's producer status, the specific phytonutrient being evaluated, etc. As those skilled in the art will understand, various techniques (e.g., urinalysis, fecal analysis, plasma analysis, etc.) can be used to measure the increase in phytonutrient production, and these techniques can be used to quantify the levels of phytonutrients themselves or their metabolites (e.g., present in the urine, blood, etc. of a subject). It should be understood that administration of plant-based functional compositions can be used to supplement the in vivo production of phytonutrient producers, non-phytonutrient producers, and weak phytonutrient producers, etc.

[0026] Many phytonutrients mediate specific therapeutic and / or preventative effects and can therefore be used to treat or improve the condition of a subject. As used herein, the terms “treatment” or “treating” are used interchangeably and refer to a method for obtaining a beneficial or desired outcome, including but not limited to therapeutic and / or preventative benefits. A therapeutic benefit may refer to the eradication or improvement of the underlying condition being treated. Furthermore, a therapeutic benefit can be achieved by eradicating or improving one or more physiological symptoms associated with the underlying condition, resulting in an improvement observed in the subject, although the subject may still suffer from the underlying condition. Preventative effects include delaying, preventing, or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, stopping, or reversing the progression of a disease or condition, or any combination thereof. For preventative benefits, a subject at risk of developing a specific disease or a subject reporting one or more physiological symptoms of a disease may undergo treatment, even if the disease may not yet have been diagnosed.

[0027] Typically, the methods may include or be used to improve conditions such as those described above, i.e., by mediating the production of phytonutrients in the subject (e.g., via microbial metabolism), wherein the phytonutrients mediate their effects in the subject. For example, in some embodiments, the methods may be used to improve conditions via anti-inflammatory, antioxidant, antibacterial, autophagy, mitochondrial, intestinal barrier, microbiota composition, immune, neurological, and / or anti-aging effects. In these or other embodiments, the methods may be used to improve conditions affecting a subject's endurance, heart health, skin health, insulin sensitivity, eye health, cognition (e.g., memory), liver health, elevated cholesterol, hormonal balance, reproductive health, and / or digestive health. For example, the methods may be used to improve such conditions by improving visual function, reducing inflammation (e.g., via inhibiting pro-inflammatory enzymes such as lipoxygenase (LPO) and cyclooxygenases (COX-1, COX-2)), reducing oxidant concentrations, increasing vasodilation, controlling blood glucose and / or lipid levels, inhibiting stages of cancer processes (e.g., by increasing apoptosis and / or reducing metastasis, signal transduction, transcription factor activity, cell adhesion, etc.), or combinations thereof.

[0028] In light of the foregoing, it should be understood that there are no limitations on the specific biological effects conferred on subjects via mediating the production of phytonutrients, and these effects can be diverse and varied in terms of the overall health benefits and mechanisms of action conferred on subjects. For example, in some embodiments, the method includes mediating the production of 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) (i.e., a phytonutrient) from cyanidin-3-glucan (i.e., a phytonutrient precursor compound) to influence biological processes involving cyclin-dependent kinases (CDK 1,2,4) and / or cell proliferation, thereby improving conditions related to colorectal cancer. In these or other embodiments, the method includes mediating the production of short-chain fatty acids, parargonidin-3-O-glucan, and / or another phytonutrient from anthocyanins (i.e., phytonutrient precursor compounds) to influence intestinal barrier function, autophagy, or biological processes involving MAPK and / or NF-κB, thereby improving conditions related to intestinal barrier function, cellular aging, neuroprotection, and / or hyperglycemia.

[0029] In these or other embodiments, the method includes mediating the production of phytonutrients from taraxerin (i.e., phytonutrient precursor compounds) to influence biological processes involving CBR, ERα / β, EGFR, BCRP, and / or SGLT-1, thereby improving conditions involving cardiovascular health, neuroprotection, and / or hyperglycemia. In these or other embodiments, the method comprises mediating the production of hesperidin, dihydrocaffeic acid, isoflavone, 4-hydroxyphenylacetic acid, dihydroferruvic acid, ferulic acid, resorcinol, phloroglucinol, 2,4-dihydroxyphenylacetic acid, 4-hydroxybenzoic acid, phloroglucinic acid, trichomoniatic acid, hydrogenated cinnamic acid, 3-(3'-hydroxyphenyl)propionic acid, protocatechuic acid, and / or hippuric acid (i.e. phytonutrients) from hesperidin and / or naringin (i.e., phytonutrient precursor compounds) to influence biological processes involving RANKL-induced osteoclastogenesis, SCFA production, transepithelial electrical resistance (TEER), and / or claudin, thereby improving conditions involving bone loss due to intestinal leakage, intestinal barrier dysfunction, gastrointestinal inflammation, and / or metabolic syndrome (MetS). In these or other embodiments, the method includes mediating the production of hydrogenated caffeic acid (HCAF), dihydroxyphenylacetic acid (dOHPA), and hydrogenated ferulic acid (HFER) (i.e. phytonutrients) from polyphenols (i.e., phytonutrient precursor compounds) to influence biological processes in the distal colonic mucosa involving levels of cytokines IL-1β, IL-8, and TNF-α, malondialdehyde (MDA) levels, and / or oxidative DNA damage (e.g., measured as 8-oxo-2'-deoxyguanosine levels), thereby improving conditions involving inflammation. In these or other embodiments, the method includes mediating the production of urolithin A (i.e., phytonutrient) from ellagic acid (i.e., a phytonutrient precursor compound) to influence biological processes involving reduced inflammatory markers (iNOS, cyclooxygenase-2, PTGES, and PGE (2)) in the colonic mucosa, mitochondrial function, weakened UA with Aβ deposition, periplasmic microglial proliferation and astrocyte proliferation in the cortex and hippocampus, AMPK activation, activation of P65NF-κB and P38MAPK, and / or degradation of Bace1 and APP, thereby improving conditions involving neurological and / or colonic inflammation, skeletal muscle health, cellular aging, and / or memory impairment. In these or other embodiments, the method includes mediating the production of phytonutrients from anthocyanins (i.e., phytonutrient precursor compounds) to influence biological processes in HepG2 cells involving high glucose, palmitic acid-induced ROS overproduction, mitochondrial membrane collapse, and / or glutathione depletion, thereby improving conditions involving oxidative stress / damage and / or diabetes (e.g., via anti-diabetic activity).

[0030] The phytofunctional composition can be administered as needed, daily, several times a day, or in any suitable regimen to achieve the desired results. In the methods described, the frequency of administration can depend on several factors, including the desired level of prevention or improvement. Typically, the regimen involves administering the phytofunctional composition to the subject once or twice daily, for example, including administration in the morning and / or evening. The amount of composition administered to the subject during each administration period can depend on several factors, including the level of desired results and the specific composition used. Typically, the phytofunctional composition is administered in a therapeutically or physiologically effective amount. As used herein, the term "therapeutically effective amount" refers to the amount (i.e., quantity) of the composition (e.g., the phytofunctional composition of this embodiment) required to achieve a specific therapeutic and / or preventive effect (e.g., treating a patient). Similarly, as used herein, the term "physiologically effective amount" refers to the amount of the composition required to achieve the desired physiological effect. Such effective amounts are typically measured and / or expressed in g / day or derivatives thereof (e.g., mg / day). Typically, the phytofunctional composition is administered in an amount that effectively provides the subject with phytonutrients. In some embodiments, the phytofunctional composition is administered in an amount that effectively alters or improves the subject's phytonutrient producer status. In these or other embodiments, the plant-based functional composition is administered in an amount that effectively improves the subject's medical condition.

[0031] Generally, the plant functional compositions used in the methods are not limited in terms of formulation, auxiliary ingredients, form, or number of functions. Instead, plant functional compositions can vary, and many can be formulated in any manner consistent with this disclosure. As described above, plant functional compositions are used in the methods to impart health benefits to subjects, such as by improving the subject's phytonutrient producer status regarding a specific phytonutrient or a disease / condition associated with it.

[0032] Plant-based functional compositions contain active agents. The active agents are not limited and can be any agent suitable for improving the phytonutrient producer status of the subject. Typically, the active agents comprise probiotics, prebiotics, and / or phytonutrient precursor compounds, or probiotics, prebiotics, and / or phytonutrient precursor compounds.

[0033] In some embodiments, the active agent is a probiotic or contains probiotics. As used herein, the term "probiotic" can refer to one or more microorganisms that, when properly administered, can confer health benefits to a host or subject. Therefore, in some embodiments, the plant-based functional composition comprises a population of microorganisms. One or more probiotic microorganisms can be obtained in various ways. In some embodiments, a population sample is collected from a human fecal sample and subsequently cultured and processed into probiotics. Examples of suitable probiotics typically include those from the family Rhodotorulaceae (…). Coriobacteriaceae ) and / or Clostridium spheroides-rectum ( Clostridium coccoides–Eubacterium rectale Members of the cluster and various Lactobacillus genera ( Lactobacillus sp. ) and Bifidobacterium spp. Bifodobacterium sp. Some examples of suitable probiotics include probiotics or combinations thereof from families such as Bacteroidetes, Clostridium, Prevotella, Eubacteria, Ruminococci, Bifidobacteria, Lactobacilli, Enterobacteriaceae, Yeast, Methanobacteriaceae, etc. Some specific examples include: C. orbiscidens Oxidogenic Eubacteria (Eubacterium oxidoreducens) Bacillus subtilis (B. subtilus) Diplostomum (Bacteroides distasonis) Bacteroides monomorpha (Bacteroides uniformis) ; Oval-shaped Bacteroides (Bacteroides ovatus) Enterococcus faecalis (Enterococcus casseliflavus) ; Bacillus filamentosa (Eubacterium ramulus) Lactobacillus-Enterococcus (Lactobacillus– Enterococcus) Trichophyceae (Lachnospiraceae) Lactobacillus johnsonii (L johnsonii) Bifidobacterium chainii (Bifidobacterium catenulatum) Bifidobacterium pseudochain (Bifidobacterium pseudocatenultum) ; Gordonibacter urolithinfaciens ; Gordonibacter pamelaeae Clostridium spherulites (Clostridium coccoides) Clostridium perfringens (Clostridium leptum) Intermediate streptococci (Streptococcus intermedius) ; Ruminococcus productus Aggregates (Eggerthella (sp.)Julong 732 Enterococcus faecalis EPI1 (Enterococcus faecium EPI1) Lactobacillus mucosa EPI2 (Lactobacillus mucosae EPI2) ; *Goldelda elongata* EPI3 (Finegoldia magna EPI3) ; fecal bacteria (Feacalibacterium) ; Slackia isoflavoniconverten ; and Egerte bacteria (Eggerthella sp.) ; and its various derivatives and / or combinations.

[0034] In some embodiments, the active agent is a prebiotic or contains a prebiotic. As used herein, the term "prebiotic" refers to a compound or combination of compounds that cannot be digested by a subject (e.g., an animal) but can selectively stimulate the growth and / or activity of one or a limited number of beneficial bacteria in the subject's microbiome. Additionally, the term "prebiotic effect" refers to a selective, prebiotic-induced stimulation of the growth and / or activity of one or a limited number of bacteria (e.g., Bifidobacteria, Lactobacillus, etc.) in the host's microbiome. Generally, prebiotics are not limited and can be any compound or combination of compounds that stimulates the growth of one or more microorganisms in the host's microbiome, including those exemplified herein with respect to probiotics. Prebiotics can stimulate such growth directly (e.g., by providing nutrients to microorganisms) and / or indirectly (e.g., by preventing the growth of competing microorganisms). Examples of suitable prebiotics typically include fiber, such as soluble fiber (i.e., those soluble in water) and insoluble fiber (i.e., those insoluble in water). Some examples of fibers include starch, non-starch polysaccharides and oligosaccharides, carbohydrate fibers, lignans, and combinations thereof. Specific examples of suitable fibers used as prebiotics or as prebiotics include cellulose, hemicellulose, arabinoxylan, fructooligosaccharides, inulin, oligofructan, galactooligosaccharides, gums, mucilage, pectin, dextrin, maltodextrin, synthetic carbohydrates, polydextrose, methylcellulose, hydroxypropyl methylcellulose, waxes, phytates, cutin, saponins, cork resins, tannins, chitosan, alginate, curdian, cork resins, lignin, chitosan, and combinations thereof.

[0035] In specific embodiments, the prebiotic comprises, or is substantially composed of, fiber and / or starch, or fiber and / or starch. In such embodiments, the fiber and / or starch are not limited and can be any fiber and starch exemplified in the general and specific examples of fiber and starch herein. In some embodiments, the prebiotic comprises, or is substantially composed of, resistant starch, or resistant starch, which is starch or starch digestion products that are not digested and / or absorbed in the stomach or small intestine of the subject but are suitable for delivery to the large intestine of the subject (e.g., for consumption, fermentation, and / or metabolism by the subject's gut microbiota). In particular, in embodiments in which the subject is a mammal (e.g., a human), examples of suitable resistant starch used as a prebiotic or as a prebiotic generally include those classified by those skilled in the art as Class I resistant starch (e.g., starch that is physically inaccessible or indigestible to the subject, such as starch found in seeds, legumes, and unprocessed whole grains), Class II resistant starch (e.g., starch that is resistant to enzymatic degradation in the subject's gut, including those that are inaccessible to enzymes due to the conformation of starch, such as high amylose corn starch), Class III resistant starch (e.g., starch formed when starchy foods (e.g., pasta) are cooked and cooled), and / or Class IV resistant starch (e.g., starch that is chemically modified to resist digestion).

[0036] In certain embodiments, the active agent is a phytonutrient precursor compound or contains a phytonutrient precursor compound. The phytonutrient precursor compound is not limited and can be any compound derived from a plant source and capable of being metabolized by microorganisms into a phytonutrient. In some embodiments, the phytonutrient precursor compound is a plant raw material. In these or other embodiments, the phytonutrient precursor compound is a processed plant material, such as a compound or combination of compounds derived from plant material via natural and / or synthetic methods, distillation, hydrolysis, or otherwise. In certain embodiments, the phytonutrient precursor compound is partially metabolized plant material (e.g., produced by microbial metabolism / digestion). Such partially metabolized plant material typically includes intermediates formed during the metabolic transformation of plant material into phytonutrients. Many intermediates are typically formed during the transformation (e.g., post-metabolism) of plant material (e.g., compounds extracted from it) into their respective phytonutrients. Therefore, the phytonutrient precursor compound can be any such intermediate or combination of such intermediates. In this way, administering the phytonutrient precursor compound to the subject can bypass the microbial metabolic steps that would otherwise be necessary to produce the phytonutrient (e.g., from the plant raw material).

[0037] General examples of plants containing suitable phytonutrient precursors typically include fruits and / or berries, vegetables, nuts and / or seeds, legumes, genus plants, herbs and / or spices, or combinations thereof. Some specific examples of such plants include red onions, capers, citrus fruits, cranberries, apples, grapes, sweet potatoes, blueberries, blackcurrants, pomegranates, cranberries, walnuts, soybeans, flax or other seeds, cruciferous vegetables or other leafy green vegetables, and / or green tea. Further examples of such plants may include whey, rice, wheat, legumes, peas, potatoes, fruits, buckwheat, and / or corn.

[0038] Examples of types of phytonutrient precursor compounds suitable for use according to this disclosure generally include proteins, peptides, complex amino acids, lipids (e.g., fatty acids, sterols, pentenols, glycolipids, glycerides, glycerophospholipids, polyketides, sphingolipids, etc.), carotenoids, phenolic plant compounds, alkaloids, glucosinolates, polysaccharides, terpenes, betaine pigments, polyacetylenes (e.g., falcanthol, falcanthidyldiol, ginsenoside diol, onanthetol, etc.), capsaicins (e.g., capsaicin, hihydrocapsaicin, hycapsaicin, nolanthylamine, etc.), Allium compounds (e.g., metiin, propiin, isoalliin, etc.), lectins (e.g., concanavalin A, ricin, lectins such as wheat germ lectin, peanut lectin, soybean lectin, etc.), organosulfur plant compounds (e.g., isothiocyanates, indoles, allyl sulfides, etc.), and their derivatives, modifiers, and combinations thereof. Specific examples of carotenoid phytonutrient precursor compounds include carotenes (e.g., α-carotene, β-carotene, etc.), cryptoxanthin, zeaxanthin, astaxanthin, lycopene, lutein, etc., as well as their derivatives, modifications, and combinations. Specific examples of phenolic phytonutrient precursor compounds include phenols, phenolic acids (e.g., benzoic acid and hydroxybenzoic acid, such as gallic acid, protocatechuic acid, vanillic acid, syringic acid, etc.; cinnamic acid and hydroxycinnamic acid, such as p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, etc.), flavonoids, flavonols (e.g., quercetin, kaempferol, myricetin, galangin, fisetin, etc.), flavones (e.g., apigenin, succinate, luteolin, etc.), flavanols (e.g., catechin, epicatechin, epigallocatechin, etc.), and flavanones (e.g., succinate, hesperidin, etc.). Examples of alkaloid precursor compounds include naringin, anthocyanins (cyanidin, hyoscyamine, paeonol, malvidin, etc.), proanthocyanidins, isoflavones (genistein, daidzein, gentiopicrin, etc.), dihydroflavonols, flavan-3-ols, flavonoids, isoflavones, tannic acid, acetophenone, phenylacetic acid, coumarins, benzophenone, zanthone, stilbene, chalcone, lignans, secoidoids, and their derivatives, modified compounds, and combinations thereof. Specific examples of alkaloid precursor compounds include amarin, berberine, caffeine, camptothecin, codeine, hyoscyamine, irinotecan, nicotine, noscarpine, oxycodone, hydroxymorphone, papaverine, and their derivatives, modified compounds, and combinations thereof.Specific examples of glucoiberin precursor compounds include glucoiberin, sinomenin, glucosinolate, gluconapoleiferin, radisin, glucosinolate, brassinolate, neobrassinolate, glucosinalbin, gluconasturtiin, and their derivatives, modifications, and combinations. Specific examples of polysaccharide precursor compounds include cellulose, hemicellulose, arabinoxylan, arabinoxygalactan, fructosaccharides, polydextrose, methylcellulose, inulin, oligofructan, oligosaccharides, gums, meilage, pectin, and their derivatives, modifications, and combinations. Specific examples of terpene precursor compounds include pyrethroids, geraniol, cucurbitacin, strigolactone, caulerpenyne, famesane, squalane, and their derivatives, modifications, and combinations. Some specific examples of beet pigment precursor compounds include beet pigment, betaine, oxalis, paclitaxel, portulaxanthin, purslane oxalis, and their derivatives, modifications, and combinations.

[0039] In some embodiments, the phytonutrient precursor compounds comprise, or are substantially composed of, quercetin, cyanidin-3-glucoside, hesperidin, ellagic acid, daidzein (+), diglucosinolate, glucosinolate, and / or epigallocatechin, or are quercetin, cyanidin-3-glucoside, hesperidin, ellagic acid, daidzein (+), diglucosinolate, glucosinolate, and / or epigallocatechin.

[0040] For the examples of phytonutrient precursor compounds described herein, modified and / or derivatives of the compounds may be altered, and can be illustrated by metabolic and / or synthetic intermediates of such compounds, as well as naturally occurring and / or synthetically modified compounds. For example, epicatechin gallate is an ester of gallic acid and epicatechin. Therefore, to illustrate the scope of some of the examples above, those skilled in the art will understand that epicatechin and epicatechin gallate can be considered derivatives and / or modified versions of each other (e.g., via esterification or hydrolysis). Therefore, it should be understood that the specific examples of phytonutrient precursor compounds are not intended to be limiting, but rather to illustrate that the methods and compositions of this disclosure are applicable to many phytonutrient precursor compounds.

[0041] In various embodiments, the plant-based functional composition comprises a variety of active agents, which can be selected independently. Typically, each active agent comprises, or optionally, at least one of the above-mentioned probiotics, prebiotics, and / or phytonutrient precursor compounds. However, in some embodiments, other active agents may be used besides those suitable for improving the phytonutrient producer status of the subject. In a particular embodiment, the plant-based functional composition comprises a combination of probiotics and phytonutrient precursor compounds. In some embodiments, the plant-based functional composition contains no or substantially no phytonutrient precursor compounds. In a specific embodiment, the plant-based functional composition is provided as a kit comprising a probiotic component and a phytonutrient precursor compound component. In such embodiments, the components of the kit may be administered together or separately (e.g., sequentially in any order).

[0042] In some embodiments, the method includes identifying an active agent to improve or otherwise alter the phytonutrient producer status of a subject. For example, the identification of the active agent may be based on the subject's phytonutrient producer status, such as in personalized treatment based on the subject's unique microbiome markers. However, identification may be based on the phytonutrient producer status of one or more hosts other than the subject. For example, in some embodiments, identifying the active agent includes conducting a cohort study to determine the phytonutrient producer status of individual individuals within the cohort. In such embodiments, the cohort study may assess the phytonutrient producer status of any number of specific phytonutrients in an individual, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more specific phytonutrients (e.g., via quality determination), and classify each individual as a producer or non-producer (or weak producer) for each specific phytonutrient assessed (collectively, an individual "phytonutrient production profile"). One or more active agents can then be selected to improve or alter the production status of each individual assessed with respect to each specific phytonutrient that is not adequately produced or metabolized. In this way, one or more active agents of a plant-based functional composition can be selected based on certain deficiencies shared by individuals within a population, regardless of the subject's own microbiome function. Therefore, this approach provides both personalized and universal treatment options, and plant-based functional compositions can exhibit increased efficacy and / or effectiveness compared to treatments that do not consider the phytonutrient production profile within the population.

[0043] In some embodiments, identifying the active agent may include conducting tests, studies, and / or model-based experiments, which may be exemplified by human intervention trials, experiments using other animal models (e.g., humanized mouse models), and / or in vitro colon models. For example, in some embodiments, identifying the active agent includes conducting human intervention studies. In such an implementation, human intervention studies may include: (i) collecting fecal and / or colonic microbiome samples and related sequence data (e.g., metagenomics, 16S RNA, etc., collectively referred to as “microbiome genetic data”) from participating subjects; (ii) administering phytonutrient precursor compounds to participating subjects; (iii) collecting blood, fecal, and / or urine samples from participating subjects; (iv) analyzing the conversion of phytonutrient precursor compounds to phytonutrients in blood, fecal, and / or urine samples; (v) analyzing microbiome genetic data associated with genes responsible for converting phytonutrient precursor compounds to phytonutrients; (vi) identifying genetic differences between phytonutrient producers and non-producers; (vii) identifying active agents (e.g., probiotics, prebiotics, and / or phytonutrient precursor compounds) to improve the producer status of participating subjects; (viii) administering to participating subjects a plant-functional composition containing the identified active agent, optionally in combination with a phytonutrient precursor compound; and (ix) monitoring the conversion of phytonutrient precursor compounds to phytonutrients. Similar workflows include in vitro colon models, intestinal models, humanized mouse models (e.g., those using germ-free mice that have been tube-fed human microbiome samples), etc.

[0044] In addition to active agents, plant-based functional compositions may contain any number of additional ingredients / components. For example, in some embodiments, the plant-based functional composition comprises an additive component, which may contain one or more additives. Examples of suitable additives for the additive component include amino acids, peptides, proteins, lipids, vitamins, carbohydrates, nucleic acids, minerals, anabolic nutrients, antioxidants, probiotic strains, anti-fatty liver agents, extracts, concentrates, oils, gums, fibers, starches, and combinations thereof. In some embodiments, the plant-based functional composition comprises an additive component, and the additive component comprises amino acids, peptides, proteins, lipids, vitamins, carbohydrates, nucleic acids, minerals, anabolic nutrients, antioxidants, probiotic strains, anti-fatty liver agents, or combinations thereof. In these or other embodiments, the additive component comprises flavoring agents, dyes, flow modifiers, preservatives, fillers, binders, dispersants, carriers, supplementary nutrients, or any combination thereof. In a particular embodiment, the additive component comprises a carrier, such as a consumable, nutrient, and / or pharmaceutical carrier, or a combination thereof. In some embodiments, the additive component comprises proteins, peptides, and / or complex amino acids based on animal, algae, and / or fungi, such as ovalbumin isolates.

[0045] In addition to the additives mentioned above, specific examples of additives suitable for additive components include pea protein isolate, isomaltose oligosaccharides, rice protein concentrate, 2'-fucosylated lactose powder, flaxseed, organic sucrose, natural flavorings, high-oleic sunflower oil, L-lysine hydrochloride, medium-chain triglycerides, L-leucine, silicon dioxide, L-valine, L-alanyl-L-glutamine, L-isoleucine, xanthan gum, vitamins, minerals, zinc gluconate, ascorbic acid, manganese gluconate, and α-acetic acid. Tocopherol esters, copper gluconate, D-biotin, retinyl palmitate, nicotinamide, cholecalciferol, calcium pantothenate, chromium pyridoxine, pyridoxine hydrochloride, riboflavin, potassium iodide, thiamine hydrochloride, L-5-methyltetrahydrofolate calcium, selenomethionine and methylcobalamin, monk fruit extract, vanilla, rosemary extract, cocoa powder, vitamin E, thiamine, riboflavin, niacin, vitamin B6, folic acid, vitamin B12, biotin, pantothenic acid, phosphorus, iodine, magnesium, zinc, selenium, copper, manganese, and combinations thereof. Of course, components other than additives can also be used in plant-based functional compositions.

[0046] Plant-based functional compositions can be administered orally to subjects, but other routes of administration are also possible. When formulated for oral administration, plant-based functional compositions can be present in discrete units (e.g., capsules, tablets, lozenges, tablets, etc.), each unit containing a predetermined amount of the plant-based functional composition (e.g., a recommended dose). However, plant-based functional compositions can be in any form, such as dry powder, solution, suspension, emulsion, etc. In some embodiments, the plant-based functional composition is a dry powder. In some embodiments, the plant-based functional composition is suitable for consumption as a liquid. For example, the plant-based functional composition can be a dry powder that is combined with a consumable liquid (e.g., water) to form a consumable liquid solution, suspension, or emulsion containing the plant-based functional composition.

[0047] In some embodiments, the plant-based functional composition may be suitable for mixing with food or beverage. As used herein, the term "food" refers to a material that can be used as food. Therefore, in some cases, the term "food" is used to describe compositions that can be consumed (e.g., by ingestion) by living organisms (e.g., mammals) for nutrition and / or maintenance. Similarly, as used herein, the term "beverage" refers to a drinkable liquid or other non-solid composition. Therefore, in some cases, the term "beverage" is used to describe non-solid (e.g., liquid, slurry, suspension, etc.) compositions that can be consumed by living organisms for nutrition and / or maintenance. Therefore, in certain cases, the terms "beverage" and "food" may overlap. In some cases, the term "nutritional composition" is used to describe food and / or beverage formulations that can be consumed or drunk by human subjects to obtain nutrition. Therefore, in some embodiments, the plant-based functional composition is a food or beverage, or a component of a food or beverage.

[0048] In these or other embodiments, plant-based functional compositions may be further defined as food additives. As used herein, the term "food additive" refers to an ingredient, additive, component, or supplement suitable for incorporation into foods and / or beverages to impart host technology, nutritional, and / or health benefits (i.e., functionality) to the consuming food and / or beverage. Therefore, such benefits may be closely related to the presence of phytonutrients in the subject. Food additives can be incorporated into different types of foods, including but not limited to medical foods, dietary foods, and supplements. Certain aspects of these embodiments may include the use of plant-based functional compositions as food additives, and the use of plant-based functional compositions in methods of preparing foods and / or beverages.

[0049] Typically, when used as a component of a food or beverage, the food or beverage comprises a mixture of a plant-based functional composition and one or more raw material products, liquids, supplements, or combinations thereof. However, in some embodiments, the plant-based functional composition itself may be further defined as a food or beverage composition, depending on the amount, nature, and identity of the individual additives and components present in the plant-based functional composition, such as those described above. Therefore, it should be understood that the embodiments described herein with respect to plant-based functional compositions are intended to equally include foods or beverages, food or beverage products, and / or food supplements containing plant-based functional compositions. Consequently, any amount and / or instance of such components described herein with respect to plant-based functional compositions themselves can be equally applied to foods or beverages containing plant-based functional compositions.

[0050] In some embodiments, a food or beverage containing a plant-based functional composition is further defined as a nutritional composition. In these or other embodiments, the nutritional composition is in the form of a dried food concentrate, which can be mixed with a liquid or food and subsequently consumed. It should be understood that a nutritional composition is different from a vaccine, and the plant-based functional compositions described herein may contain no or substantially no vaccines.

[0051] In some embodiments, the plant-based functional composition may be further defined as a nutritional supplement or complete nutrient. As used herein, the term "supplement" refers to a concentrated source of nutrients or other substances having nutritional or physiological effects, intended to supplement a normal diet. For example, a plant-based functional composition may be formulated to provide a mammal (e.g., a human) with at least 5%, or at least 10%, or at least 25%, or at least 50%, or at least 75%, or at least 90% of the daily calorie requirement required by the mammal, by consuming the plant-based functional composition. However, it should be understood that daily calorie requirements depend on several factors, including the mammal's sex, height, and / or age, and therefore the percentage of calorie requirements provided by the plant-based functional composition will depend on the specific person consuming the nutritional composition. For example, a 30-year-old male weighing 80 kg and 180 cm tall has a daily calorie requirement of approximately 2900 cal (calories) to maintain his / her weight, while a 30-year-old female weighing 55 kg and 165 cm tall has a daily calorie requirement of approximately 2100 cal (calories) to maintain her / her weight. In some embodiments, the food or beverage is further defined as a medical food. Therefore, it should be understood that medicinal foods contain plant-based functional compositions and may be the same as or different from the aforementioned nutritional compositions. As used herein, the term "medical food" is generally used to refer to foods intended for specific dietary purposes, such as foods formulated for dietary management of medical conditions (e.g., based on scientific or medical evaluation). However, it should be understood that the term "medical food" may have one or more specific definitions, depending on factors such as geographical location, specific purpose, regulatory body, etc. For example, in some cases, the term medical food can be defined as a food formulated for intestinal consumption or administration under the supervision of a physician and intended for the specific dietary management of a disease or condition, based on recognized scientific principles and established through medical evaluation to establish unique nutritional requirements for said disease or condition (see, for example, section 5(b) of the Orphan Drug Act (21 USC 360ee (b)(3)), which is incorporated herein by reference. In these or other cases, the term medical food can be defined as a food intended for a specific dietary purpose, such as a food that has been specially processed or formulated to meet the specific needs of a person who: (a) has a physical or physiological condition due to a disease, ailment, or injury; or (b) achieves a specific effect for said person through controlled food intake, including but not limited to weight loss (see, for example, section B.24.001 of the Canadian Food and Drug Regulations (FDR, CRC, c. 870, amended June 13, 2017), which is incorporated herein by reference).

[0052] In some embodiments, the plant functional composition is further defined as an animal food. In such embodiments, the plant functional composition is typically formulated for ingestion by one or more non-human animals, such as livestock including cattle, pigs, horses, sheep, goats, poultry, and fish; domesticated companion species such as dogs, cats, fish, and rodents; non-domesticated wild animals such as deer, moose, elk, migratory and non-migratory poultry; those non-human animals described herein; and combinations thereof. In certain circumstances, administering a plant functional composition as an animal food to a non-human subject (e.g., an animal) can result in an increased production of one or more commodities (e.g., eggs, meat, milk, wool, etc.) by the host.

[0053] The following examples are intended to illustrate the present invention and should not be construed as limiting the scope of the invention in any way.

[0054] Example 1: Status of Phytonutrient Producers The phytonutrient producer status of 11 subjects (referred to as "Subjects 1-11" or "S1"-"S11") was assessed by determining the microbial metabolism of various phytonutrient precursor compounds. Specifically, as described in SE Ladirat et al., High-throughput analysis of the impact of antibiotics on the human intestinal microbiota composition, Journal of Microbiological Methods 92 (2013), pp. 387-397 (incorporated hereby by reference), microarrays representing the gut microbiota were constructed by culturing in vitro ferments of fecal samples obtained from each donor using selected phytonutrient precursor compounds. The metabolism of the phytonutrient precursor compounds in each assay was subsequently determined by monitoring their conversion (+), partial conversion (±), or no conversion (-) over time. The results of the microarrays and the various phytonutrient precursor compounds used therein are illustrated in Table 1 below.

[0055] Table 1: Status of Phytonutrient Producers <![CDATA[ Phytonutrient precursor compounds ]]> <![CDATA[ S1 ]]> <![CDATA[ S2 ]]> <![CDATA[ S3 ]]> <![CDATA[ S4 ]]> <![CDATA[ S5 ]]> <![CDATA[ S6 ]]> <![CDATA[ S7 ]]> <![CDATA[ S8 ]]> <![CDATA[ S9 ]]> <![CDATA[ S10 ]]> <![CDATA[ S11 ]]> hesperidin + + + + ± + + + + + + Epigallocatechin + + ± + + + + + + + + Open-ring isolarcisinol diglucoside + + ± + + ± ± ± + + + Quercetin - + + + - + + - - + - cyanidin-3-glucoside ± ± + ± ± + + ± + + + Ellagic acid ± ± ± - - - - ± - ± - daidzein - - - - - - - - - - - As shown in Table 1, all subjects except two (S7 and S11) exhibited unique metabolic fingerprints, with varying abilities to metabolize phytonutrient precursor compounds.

[0056] Example 2: Identification of active compounds for mediating the state of phytonutrient producers To identify active compounds for use in plant-based functional compositions, the ability of various probiotics to metabolize phytonutrient precursor compounds was evaluated. Specifically, bacterial strains were obtained and stored at -80°C, then thawed, and the resulting cell suspensions were plated onto culture plates using an inoculation needle and incubated for 3–5 days. The bacterial strains, culture media, and culture conditions are described in Table 2 below.

[0057] Table 2: Probiotics used in surfactants Three days later, colonies were taken from each culture and plated again on another agar plate to check purity. The cultures were then incubated under optimal conditions for another 3-5 days, during which time another colony was taken and plated on an agar plate. The cultures were then incubated at 37°C under anaerobic conditions for 3-5 days to allow the strains to adapt to the selection culture conditions.

[0058] 48 hours and 24 hours before the experiment, colonies were transferred to culture media (MSRB, BHIB, GGB, MRSph6.8B and RCMB, kept anaerobic for at least 48 hours before inoculation) and incubated on shaking plates at 37°C and 450 rpm for 48 hours or 24 hours under anaerobic conditions.

[0059] Various phytonutrient precursor compounds were dissolved in DMSO to a concentration of 10 mg / ml. Twenty-four hours before the experiment, the compounds were mixed together and diluted in DMSO to a concentration of 0.5 mg / ml. Triplets of the compound mixture and DMSO (control) were transferred to 2.0 mL deep-well plates, and the resulting plates were sealed with a breathable sealant and stored anaerobically in wide-mouth bottles at 4°C.

[0060] On the day of the experiment, all steps were performed under anaerobic conditions, and the OD of each strain was measured. 600 Dilute to OD in culture medium 600 The concentration was 0.5. The strain was then diluted 100-fold in the culture medium, and 990 μL of the diluted strain-medium mixture was added to 10 μL of compound / DMSO in each well of the preparation plate. The plate was then incubated on a shaking plate for 48 hours under anaerobic conditions at 37°C and 450 rpm.

[0061] Samples (100 μL) were collected from each well at t=0, 24, and 48 hours and subjected to metabolite analysis (LC-MS) to determine the consumption (“yes”) and partial metabolism (“no”) of phytonutrient precursor compounds over time. ") or no conversion ("No"), the results of which are presented in Tables 3 and 4 below.

[0062] Table 3: Metabolic activity of probiotic bacteria selected for active agents <![CDATA[ nourish ]]> <![CDATA[ Quercetin ]]> <![CDATA[ cyanidin-3-glucoside ]]> <![CDATA[ Epigallocatechin ]]> <![CDATA[ hesperidin ]]> #1 no no no no #2 no no no no #3 no no no no #4 no no no no #5 no yes no no #6 no no no no #7 no yes no no #8 no yes no no #9 no no no no #10 no yes no yes #11 no no no #12 no yes no no #13 no yes no no #14 no yes yes no #15 no yes no #16 no yes no #17 no yes no no #18 no yes no no #19 no yes yes no #20 no yes no no #21 no yes no no #22 no yes no no #23 no yes no no #24 no yes no no #25 no yes no #26 no yes no #27 no yes no no #28 no yes no no Table 4: Metabolic activity of probiotic bacteria selected for active agents <![CDATA[ nourish ]]> <![CDATA[ Ellagic acid ]]> <![CDATA[ daidzein ]]> <![CDATA[ Open-ring isolarcisinol diglucoside ]]> #1 no no no #2 no no no #3 no no no #4 no no no #5 no no no #6 no no no #7 no no no #8 no no no #9 no no no #10 no no #11 no no #12 no no no #13 no no no #14 no no no #15 no no no #16 no no no #17 no no no #18 no no no #19 no no no #20 no no no #21 no no no #22 no no no #23 no no no #24 no no no #25 no no no #26 no no no #27 no no no #28 no no no In Tables 3 and 4 above, record "Yes" to indicate that the corresponding phytonutrient precursor compounds (i.e., quercetin, cyanidin-3-glucoside, epigallocatechin, hesperidin, ellagic acid, daidzein (+), or diglucan diglucan) were completely metabolized within 24 and / or 48 hours. Record "No" to indicate that the metabolism of the corresponding phytonutrient precursor compounds was not observed within 24 or 48 hours. Record " "To indicate the partial metabolism / consumption of the corresponding phytonutrient precursor compounds observed at 24 hours and / or 48 hours."

[0063] Mixtures of each phytonutrient precursor compound and its metabolites were prepared and diluted in used culture medium to verify the separation and sensitivity observable by LC-MS at lower concentrations. Using 50:50 (%) used culture medium / formic acid, the phytonutrient precursor compounds were well detectable at approximately 2 μg / mL (1:10 dilution).

[0064] As shown in Tables 3 and 4, the selected probiotic strains can be used or served as activators in plant-based functional compositions to metabolize certain phytonutrient precursor compounds via microbial metabolism. These activators can be readily identified via microarrays in a convenient and efficient manner for a wide range of phytonutrient precursor compounds. Furthermore, since phytonutrient precursor compounds are not universally metabolized, as demonstrated in Example 1 above, activators can be selected based on the subject's producer status, for example, via a personalized metabolome.

[0065] As those skilled in the art will understand, in a first embodiment, this disclosure provides a method for altering the phytonutrient producer status of a subject, wherein the method comprises: administering the subject a phytofunctional composition, wherein the phytofunctional composition comprises a phytonutrient precursor compound and an active agent comprising probiotics and / or prebiotics, wherein the active agent is adapted to mediate the production of a preselected phytonutrient from the phytonutrient precursor compound in the subject's gastrointestinal tract; thereby altering the subject's phytonutrient producer status.

[0066] In a second embodiment, the method of the first embodiment further includes identifying the subject's phytonutrient producer status by assessing the level of a preselected phytonutrient or a preselected phytonutrient precursor compound in the subject before administering the plant functional composition to the subject.

[0067] In a third embodiment, a further feature of the method described in the first or second embodiment is that the identification of the subject's phytonutrient producer status is performed in vitro as follows: obtaining a sample from the subject's gastrointestinal tract; and quantifying the amount of the preselected phytonutrient in the sample.

[0068] In the fourth embodiment, a further feature of the method described in the third embodiment is that the sample is further defined as a fecal sample.

[0069] In a fifth embodiment, the method of the fourth embodiment further includes culturing the fecal sample in the presence of the preselected phytonutrient precursor compound before quantifying the amount of the preselected phytonutrient in the sample.

[0070] In a sixth embodiment, the method of any one of the first to fifth embodiments is further characterized in that the preselected phytonutrient is further defined as a first preselected phytonutrient; wherein identifying the phytonutrient producer status further comprises assessing the level of at least one of a second preselected phytonutrient and a second preselected phytonutrient precursor compound in the subject, wherein the second preselected phytonutrient is a microbial metabolite of the second phytonutrient precursor compound; and wherein the plant functional composition is adapted to mediate the production of the second preselected phytonutrient in the gastrointestinal tract of the subject.

[0071] In the seventh embodiment, a further feature of the method described in the sixth embodiment is that the first and second preselected phytonutrients are metabolically unrelated.

[0072] In the eighth embodiment, a further feature of the method in any one of the first to seventh embodiments is that: (i) the preselected phytonutrient is a microbial metabolite of the phytonutrient precursor compound; (ii) mediating the production of the preselected phytonutrient is further defined as increasing the level of microbial metabolism that produces the preselected phytonutrient in the gastrointestinal tract of the subject; or (iii) both (i) and (ii).

[0073] In the ninth embodiment, a further feature of the method described in any one of the first to eighth embodiments is that the active agent of the plant functional composition comprises probiotics.

[0074] In the tenth embodiment, a further feature of the method described in the ninth embodiment is that the probiotic comprises a bacterial strain capable of metabolizing the phytonutrient precursor compound to increase the level of the preselected phytonutrient in the gastrointestinal tract of the subject.

[0075] In the eleventh embodiment, a further feature of the method described in the tenth embodiment is that the probiotic comprises: (i) a species of Bifidobacterium; (ii) a species of Lactobacillus; or (iii) both of (i) and (ii).

[0076] In the twelfth embodiment, a further feature of the method described in any one of the first to eleventh embodiments is that altering the phytonutrient producer status of the subject is further defined as increasing the production of the preselected phytonutrient in the gastrointestinal tract of the subject.

[0077] In the thirteenth embodiment, a further feature of the method described in any one of the first to twelfth embodiments is that the plant functional composition is orally administered to the subject.

[0078] In the fourteenth embodiment, a further feature of the method described in any one of the first to thirteenth embodiments is that the plant functional composition is administered to the subject in a dose formulation during treatment.

[0079] In the fifteenth embodiment, a further feature of the method described in the fourteenth embodiment is the selection of the amount and timing of each dose to maintain the altered phytonutrient producer state for most of the treatment period.

[0080] In the sixteenth embodiment, a further feature of the method described in any one of the first to fifteenth embodiments is that the phytonutrient precursor compound comprises: (i) quercetin; (ii) cyanidin-3-glucoside; (iii) epigallocatechin; (iv) hesperidin; (v) ellagic acid; (vi) diglucoside of seco-larch resinol; (vii) a metabolite of any one of (i)-(vi); or (viii) any combination of (i)-(vii).

[0081] In the seventeenth embodiment, a further feature of the method described in any one of the first to sixteenth embodiments is that the phytonutrient is preselected from 2,4,6-trihydroxybenzoic acid, parargonidin-3-O-glucoside, hesperidin, urolithin A, hydrogenated ferulic acid, hydrogenated caffeic acid, and dihydroxyphenylacetic acid.

[0082] As those skilled in the art will also understand, in the eighteenth embodiment, this disclosure further provides a plant-based functional composition for mediating the microbial metabolism of a subject, the plant-based functional composition comprising a phytonutrient precursor compound and an active agent comprising probiotics and / or prebiotics, wherein the active agent is adapted to mediate the production of a preselected phytonutrient from the phytonutrient precursor compound in the gastrointestinal tract of the subject.

[0083] In the nineteenth embodiment, a further feature of the plant functional composition of the eighteenth embodiment is that the phytonutrient precursor compound comprises: (i) quercetin; (ii) cyanidin-3-glucoside; (iii) epigallocatechin; (iv) hesperidin; (v) ellagic acid; (vi) diglucoside of seco-larch resinol; (vii) a metabolite of any one of (i)-(vi); or (viii) any combination of (i)-(vii).

[0084] In the twentieth embodiment, a further feature of the plant functional composition described in the eighteenth or nineteenth embodiment is that the active agent of the plant functional composition comprises probiotics.

[0085] In the twenty-first embodiment, a further feature of the plant-based functional composition of the twenty-tenth embodiment is that the probiotic comprises a bacterial strain capable of metabolizing the phytonutrient precursor compound to increase the level of the preselected phytonutrient in the gastrointestinal tract of the subject.

[0086] In the twenty-second embodiment, a further feature of the plant functional composition of the twenty or twenty-first embodiment is that the probiotic comprises: (i) a species of Bifidobacterium; (ii) a species of Lactobacillus; or (iii) both of (i) and (ii).

[0087] In the twenty-third embodiment, and any one of the eighteenth to twenty-second embodiments, the plant functional composition is further characterized in that the phytonutrient is preselected from 2,4,6-trihydroxybenzoic acid, parargonidin-3-O-glucoside, hesperidin, urolithin A, hydrogenated ferulic acid, hydrogenated caffeic acid, and dihydroxyphenylacetic acid.

[0088] In the 24th embodiment, a further feature of the plant functional composition of any one of the 18th to 23rd embodiments is that the phytonutrient precursor compound is further defined as a first phytonutrient precursor compound, and the preselected phytonutrient is further defined as a first preselected phytonutrient, wherein the plant functional composition further comprises a second phytonutrient precursor compound, and wherein the activator is adapted to mediate the production of the first preselected phytonutrient from the first phytonutrient precursor compound and the production of the second preselected phytonutrient from the second phytonutrient precursor compound in the gastrointestinal tract of the subject.

[0089] The terms “comprising” or “comprise” are used in their broadest sense herein to mean and encompass the concepts of “including,” “include,” “substantially constitute,” and “compose of.” The use of “for example,” “eg,” “suchas,” and “comprising” to list illustrative examples is not limited to the examples listed. Therefore, “for example” or “such as” means “for example but not limited to” or “such as but not limited to,” and covers other similar or equivalent examples. The term “about” as used herein is used to reasonably cover or describe minute variations in numerical values ​​measured by instrumental analysis or as a result of sample processing. Such minute variations can be on the order of ±0-10%, ±0-5%, or ±0-2.5% of the numerical value. Furthermore, when associated with a range of numerical values, the term “about” applies to two numerical values. Moreover, the term “about” may also apply to numerical values ​​even if not explicitly stated otherwise.

[0090] Generally, as used herein, a hyphen “-” or dash “–” within a range of values ​​means “to” or “to”; ">” means “higher than” or “greater than”; “≥” means “at least” or “greater than or equal to”; “<” means “lower than” or “less than”; and “≤” means “at most” or “less than or equal to”. On an individual basis, the aforementioned patent applications, patents and / or patent application disclosures are each expressly incorporated herein by reference in their entirety in one or more non-limiting embodiments.

[0091] It should be understood that the appended claims are not limited to the specific compounds, compositions, or methods described in the detailed description, and may vary among specific embodiments falling within the scope of the appended claims. Regarding any Markush group relied upon herein to describe a specific feature or aspect of the various embodiments, it should be understood that different, specific, and / or unexpected results can be obtained from each of the corresponding Markush groups, independent of all other Markush members. Each Markush group can be relied upon individually and / or in combination and provides sufficient support for the specific embodiments within the scope of the appended claims.

[0092] It should also be understood that any scopes and subscopes relied upon in independently and collectively describing the various embodiments of the invention fall within the scope of the appended claims, and it should be understood that they describe and contemplate all ranges including integer values ​​and / or fractional values, even if these values ​​are not explicitly stated herein. Those skilled in the art will readily recognize that the enumerated scopes and subscopes adequately describe and enable the implementation of the various embodiments of the invention, and that such scopes and subscopes may be further described as related halves, thirds, quarters, fifths, etc. By way of example only, the range “0.1-0.9” may be further described as the lower third (i.e., 0.1-0.3), the middle third (i.e., 0.4-0.6), and the upper third (i.e., 0.7-0.9), which are individually and collectively within the scope of the appended claims and may be individually and / or collectively relied upon and provide sufficient support for specific embodiments within the scope of the appended claims. Furthermore, regarding language used to define or modify scopes, such as “at least,” “greater than,” “less than,” “not exceeding,” etc., it should be understood that such language includes subscopes and / or upper or lower limits. As another example, the scope of "at least 10" inherently includes sub-scopes of at least 10-35, at least 10-25, 25-35, etc., and each sub-scope can be relied upon individually and / or collectively to provide sufficient support for specific embodiments within the scope of the appended claims. Finally, individual numerical values ​​within the disclosed scope can be relied upon to provide sufficient support for specific embodiments within the scope of the appended claims. For example, the scope of "1-9" includes various individual integers, such as 3, and individual digits including decimal points (or fractions), such as 4.1, which can be relied upon to provide sufficient support for specific embodiments within the scope of the appended claims.

[0093] This invention has been described in an illustrative manner, and it should be understood that the terminology used is intended to be descriptive rather than restrictive. Many modifications and variations of the invention are possible based on the foregoing teachings. The invention can be practiced in ways other than those specifically described within the scope of the appended claims. The subject matter of all combinations of the independent and dependent claims (both single and multiple dependent claims) is expressly contemplated herein.

Claims

1. Use of phytonutrient precursor compounds and probiotic-containing activators in the preparation of a plant-based functional composition, said plant-based functional composition being used to alter the phytonutrient producer status of a subject, said method comprising: The phytonutrient producer status of the subject is identified by assessing the level of a pre-selected phytonutrient or a pre-selected phytonutrient precursor compound within the subject. The subject was given the plant-based functional composition, the plant-based functional composition comprising: Phytonutrient precursor compounds containing cyanidin-3-glucan, and active agents containing Bifidobacterium breve Bb-03, Bifidobacterium bifidum Bb-06, Bifidobacterium infantis Bi-26, Lactococcus lactis subsp. lactis Ll-23, Streptococcus thermophilus St-21, Lactobacillus acidophilus NCFM, Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37, Lactobacillus plantarum Lp-115, Lactobacillus acidophilus La-14, Lactobacillus casei Lc-11, Lactobacillus rhamnosus Lr-32, Lactobacillus salivarius Ls-33, Lactobacillus bulgaricus Lb-87, Lactobacillus brevis Lbr-35, Lactobacillus reuteri 1E1, Lactobacillus fermentum SBS-1, Lactobacillus gasseri Lg-36, Lactobacillus rhamnosus GG, Fusion Weissella DGCC2236 and / or Saccharomyces cerevisiae DGCC9624; Phytonutrient precursor compounds containing epigallocatechin, and active agents containing Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37, Lactobacillus plantarum Lp-115 and / or Lactobacillus rhamnosus Lr-32. Phytonutrient precursor compounds containing hesperidin, and active agents containing *Lactobacillus gasseri* Lg-36 and / or *Lactobacillus rhamnosus* GG; and / or Phytonutrient precursor compounds containing ellagic acid, and activators containing Lactococcus lactis subsp. Ll-23; The active agent is adapted to mediate the production of a preselected phytonutrient from the phytonutrient precursor compound in the gastrointestinal tract of the subject, thereby altering the subject's phytonutrient producer status. The probiotics described therein comprise bacterial strains capable of metabolizing the phytonutrient precursor compounds to increase the levels of the preselected phytonutrients in the gastrointestinal tract of the subject.

2. The use according to claim 1, wherein the plant functional composition comprises: Phytonutrient precursor compounds containing cyanidin-3-glucan, and active agents containing *Bifidobacterium breve* Bb-03, *Bifidobacterium bifidum* Bb-06, *Bifidobacterium infantis* Bi-26, *Streptococcus thermophilus* St-21, *Lactobacillus acidophilus* NCFM, *Lactobacillus rhamnosus* HN001, *Lactobacillus paracasei* Lpc-37, *Lactobacillus plantarum* Lp-115, *Lactobacillus acidophilus* La-14, *Lactobacillus casei* Lc-11, *Lactobacillus rhamnosus* Lr-32, *Lactobacillus salivarius* Ls-33, *Lactobacillus bulgaricus* Lb-87, *Lactobacillus brevis* Lbr-35, *Lactobacillus reuteri* 1E1, *Lactobacillus fermentum* SBS-1, *Lactobacillus gasseri* Lg-36, *Lactobacillus rhamnosus* GG, *Weissella fusionis* DGCC2236, and / or *Saccharomyces cerevisiae* DGCC9624; and / or Phytonutrient precursor compounds containing epigallocatechin and active agents containing Lactobacillus rhamnosus HN001 and / or Lactobacillus rhamnosus Lr-32.

3. The use according to claim 2, wherein the identification of the subject's phytonutrient producer status is performed in vitro and includes: Samples were obtained from the gastrointestinal tract of the subject; and Quantify the amount of the pre-selected phytonutrients in the sample.

4. The use according to claim 3, wherein the sample is further defined as a fecal sample, and the method further comprises culturing the fecal sample in the presence of the preselected phytonutrient precursor compound before quantifying the amount of the preselected phytonutrient in the sample.

5. The use according to any one of claims 1-4, wherein the preselected phytonutrient is further defined as a first preselected phytonutrient; wherein identifying the phytonutrient producer status further comprises assessing the level of at least one of a second preselected phytonutrient and a second preselected phytonutrient precursor compound in the subject, wherein the second preselected phytonutrient is a microbial metabolite of the second phytonutrient precursor compound; wherein the plant functional composition is adapted to mediate the production of the second preselected phytonutrient in the gastrointestinal tract of the subject; and wherein the first and second preselected phytonutrients are metabolically unrelated.

6. The use according to any one of claims 1-5, wherein: (i) the preselected phytonutrient is a microbial metabolite of the phytonutrient precursor compound; (ii) mediating the production of the preselected phytonutrient is further defined as increasing the level of microbial metabolism of the preselected phytonutrient in the gastrointestinal tract of the subject; or (iii) both (i) and (ii).

7. The use according to any one of claims 1-6, wherein the plant functional composition further comprises fiber and / or starch.

8. The use according to any one of claims 1-7, wherein: (i) The plant-based functional composition was administered orally to the subject; (ii) The subject is given the plant functional composition in a dosage form during treatment, wherein the amount and timing of each dose are selected to maintain the altered phytonutrient producer status for most of the treatment period; or (iii) both (i) and (ii).

9. The use according to any one of claims 1-8, wherein the phytonutrient precursor compound is provided as a plant extract component in the plant functional composition.

10. The use according to any one of claims 1-9, wherein the phytonutrient is preselected from 2,4,6-trihydroxybenzoic acid, parargonidin-3-O-glucoside, hesperidin, urolithin A, hydrogenated ferulic acid, hydrogenated caffeic acid, and dihydroxyphenylacetic acid.

11. A plant-based functional composition for mediating the microbial metabolism of a subject, said plant-based functional composition comprising: a phytonutrient precursor compound comprising a plant extract and an active agent comprising probiotics or prebiotics: Phytonutrient precursor compounds containing cyanidin-3-glucan, and compounds containing *Bifidobacterium breve* Bb-03, *Bifidobacterium bifidum* Bb-06, *Bifidobacterium infantis* Bi-26, *Bifidobacterium animalis* subsp. *lactotrichum* Bb-12, *Lactococcus lactis* subsp. *lactotrichum* Ll-23, *Streptococcus thermophilus* St-21, *Lactobacillus acidophilus* NCFM, *Lactobacillus rhamnosus* HN001, *Lactobacillus paracasei* Lpc-37, and *Lactobacillus plantarum* Lp-1.

15. Active agents of Lactobacillus acidophilus La-14, Lactobacillus casei Lc-11, Lactobacillus rhamnosus Lr-32, Lactobacillus salivarius Ls-33, Lactobacillus bulgaricus Lb-87, Lactobacillus pumilus Lbr-35, Lactobacillus reuteri 1E1, Lactobacillus fermentum SBS-1, Lactobacillus gasseri Lg-36, Lactobacillus rhamnosus GG, Fusion Weissella DGCC2236 and / or Saccharomyces cerevisiae DGCC9624; Phytonutrient precursor compounds containing epigallocatechin, and active agents containing Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37, Lactobacillus plantarum Lp-115 and / or Lactobacillus rhamnosus Lr-32. Phytonutrient precursor compounds containing hesperidin, and active agents containing *Lactobacillus gasseri* Lg-36 and / or *Lactobacillus rhamnosus* GG; and / or Phytonutrient precursor compounds containing ellagic acid, and activators containing Lactococcus lactis subsp. Ll-23; The active agent is adapted to mediate the production of a preselected phytonutrient from the phytonutrient precursor compound in the gastrointestinal tract of the subject; and The preselected phytonutrients are selected from 2,4,6-trihydroxybenzoic acid, parargonidin-3-O-glucoside, hesperidin, urolithin A, hydrogenated ferulic acid, hydrogenated caffeic acid, and dihydroxyphenylacetic acid.

12. The plant functional composition according to claim 11, wherein the plant functional composition comprises: Phytonutrient precursor compounds containing cyanidin-3-glucan, and active agents containing *Bifidobacterium breve* Bb-03, *Bifidobacterium bifidum* Bb-06, *Bifidobacterium infantis* Bi-26, *Streptococcus thermophilus* St-21, *Lactobacillus acidophilus* NCFM, *Lactobacillus rhamnosus* HN001, *Lactobacillus paracasei* Lpc-37, *Lactobacillus plantarum* Lp-115, *Lactobacillus acidophilus* La-14, *Lactobacillus casei* Lc-11, *Lactobacillus rhamnosus* Lr-32, *Lactobacillus salivarius* Ls-33, *Lactobacillus bulgaricus* Lb-87, *Lactobacillus brevis* Lbr-35, *Lactobacillus reuteri* 1E1, *Lactobacillus fermentum* SBS-1, *Lactobacillus gasseri* Lg-36, *Lactobacillus rhamnosus* GG, *Weissella fusionis* DGCC2236, and / or *Saccharomyces cerevisiae* DGCC9624; and / or Phytonutrient precursor compounds containing epigallocatechin and active agents containing Lactobacillus rhamnosus HN001 and / or Lactobacillus rhamnosus Lr-32.

13. The plant functional composition according to claim 11 or 12, wherein the plant functional composition further comprises fiber and / or starch.

14. The plant-based functional composition according to any one of claims 11-13, wherein the active agent of the plant-based functional composition comprises a probiotic, and the probiotic comprises a bacterial strain capable of metabolizing the phytonutrient precursor compound to increase the level of the preselected phytonutrient in the gastrointestinal tract of the subject.

15. The plant functional composition according to any one of claims 11-14, wherein the phytonutrient precursor compound is further defined as a first phytonutrient precursor compound, and the preselected phytonutrient is further defined as a first preselected phytonutrient; wherein the plant functional composition further comprises a second phytonutrient precursor compound; and wherein the activator is adapted to mediate the production of the first preselected phytonutrient from the first phytonutrient precursor compound and the production of the second preselected phytonutrient from the second phytonutrient precursor compound in the gastrointestinal tract of the subject.

16. Use of phytonutrient precursor compounds and probiotic-containing activators in the preparation of a plant-based functional composition for increasing phytonutrient production in a subject, the method comprising the steps of: The following methods were used to determine the phytonutrient producer status and phytonutrient levels within subjects in order to identify low levels of phytonutrients: Microbiome samples were obtained from the subjects; Culture microbial samples to produce metabolites of phytonutrients; Monitor the metabolites of phytonutrients to determine metabolic fingerprints; and Analyze metabolic fingerprints to determine which phytonutrients were not metabolized by the subjects; Choose probiotics that metabolize unmetabolized phytonutrients. and The subjects were given phytonutrients and selected probiotics that metabolize the phytonutrients, thereby increasing the subjects' levels and production of metabolized phytonutrients.

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