Modulation of the gut microbiome to treat mental disorders or diseases of the central nervous system

A therapeutic, disease-based technology applied in the field of modulating the gut microbiome to treat psychiatric or central nervous system disorders, able to address issues such as microbiological limitations

Pending Publication Date: 2019-05-03
HOLOBIOME INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] Current microbiological research is i...

Method used

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  • Modulation of the gut microbiome to treat mental disorders or diseases of the central nervous system
  • Modulation of the gut microbiome to treat mental disorders or diseases of the central nervous system
  • Modulation of the gut microbiome to treat mental disorders or diseases of the central nervous system

Examples

Experimental program
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Effect test

Embodiment 1

[0304] Example 1: Human feces collection

[0305] Fecal samples from healthy human donors were collected using commercially available fecal collection containers. Within 5 minutes of collection, 1 gram of feces was resuspended in 9 mL of sterile 20% glycerol in PBS and homogenized using a vortex for 30 seconds. 1 mL aliquots of this mixture were loaded into cryovials and stored at -80°C for incubation.

Embodiment 2

[0306] Example 2: Culture of Helper-Uncultured Pairs from Human Fecal Samples

[0307] All cultures were carried out in a Coy Anaerobic Vinyl chamber with 5% hydrogen and 10% CO 2 , Executed in an environment of 85% nitrogen. Serial dilutions of thawed fecal samples were prepared anaerobically in PBS and beads dispersed (7-10 beads / plate) on 1X Fastidious Anaerobic Agar (Accumedia) (FAAy) plates with 2.5% yeast extract. Plates were incubated anaerobically at 37°C for one week, and the daily appearance of colonies was followed by dotting the outside of the plate with different colored marker pens. At the end of the week, serial dilutions of late-forming colonies (appearing after 4-7 days) were prepared in PBS and beads dispersed on FAAy plates. Adjacent (< 2 cm), early-forming colonies (formed in 1-3 days) were resuspended at high density in PBS. 5 µL of this suspension was spotted onto a plate with its corresponding dispersion candidate dependent and incubated indoors for u...

Embodiment 3

[0310] Example 3: Determination of GABA as a growth factor for E. gabavorous

[0311] like Figure 2A and 2B 48-hour cultures of B. fragilis KLE1758 grown in enriched medium are shown to induce growth of E. gabavorous, which enables bioassay-driven purification of growth factors. The supernatant was solvent-separated using ethyl acetate, and the residual fraction in water induced the growth of E. gabavorous. The aqueous fraction was subsequently purified using HP-20 column chromatography, and as Figure 2C Most of the polar fractions shown induced the growth of E. gabavorous. The active fraction was then further fractionated by preparative HPLC. HPLC yielded an active fraction and NMR showed 10 compounds, mainly GABA, threonine, lactate, valine, glutamine, malonate, succinate and alanine. All the compounds were spotted on the plate with E. gabavorous dispersed, and only GABA caused induced growth, as Figure 2E -F shown. Compounds were identified by NMR analysis, which ...

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Abstract

The present disclosure relates to methods of treating at least one symptom of a mental disorder or disease of the central nervous system in a subject by modulating the amount of GABA produced in the subject's gut. The present disclosure also relates to methods of culturing the bacterial strain new bacterial strains. Also disclosed are methods of identifying bacterial strains capable of producing GABA, and engineering strains to produce GABA.

Description

[0001] Cross References to Related Applications [0002] This application claims priority and benefit to U.S. Provisional Application No. 62 / 307,991, filed March 14, 2016, the contents of which are incorporated herein by reference in their entirety. [0003] Incorporated into sequence listing [0004] The contents of the text file named "HOBE001001WOSeqList.txt", created on March 13, 2017 and having a size of 7.6 MB, are hereby incorporated by reference in their entirety. [0005] Government funding [0006] This invention was made with government support under 3R01HG005824-02S1 awarded by the National Institutes of Health. The Government has certain rights in this invention. field of invention [0007] The present invention relates to compositions and methods for treating at least one symptom of a disease in a subject. In some instances, the disorder is a psychiatric disorder or a central nervous system disorder. The present invention teaches the treatment of diseases by...

Claims

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Application Information

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IPC IPC(8): A61K35/74A61K35/745A61K35/742A61P25/00A61P25/18A61P25/22A61P25/24A61P43/00
CPCA61K35/74A61K35/745A61K35/742A61P25/22A61P25/18A61P25/24C12N9/0008C12N9/0069C12N9/1096C12N9/78C12N9/88C12Y102/01019C12Y113/12001C12Y206/01082C12Y305/03011C12Y401/01015C12Y401/01017Y02A50/30
Inventor P.斯特兰维茨K.路易斯
Owner HOLOBIOME INC
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