Microbiome response to agents

Patent metadata

Field	Value
Publication number	US-2016263166-A1
Application number	US-201515030650-A
Country	US
Kind code	A1
Filing date	Apr 28, 2015
Priority date	Apr 28, 2014
Publication date	Sep 15, 2016
Grant date	—

Abstract

A method of determining tolerance to an agent in a healthy subject is disclosed. The method comprises:
(a) determining a signature of a microbiome in a sample of the healthy subject who has been subjected to the agent or condition; and (b) comparing the signature of the microbiome of the healthy subject to at least one reference signature of a pathological microbiome, wherein when the signature of the microbiome of the healthy subject is statistically significantly similar to the reference signature of the pathological microbiome, it is indicative that the healthy subject is intolerant to the agent.

First claim

1 . A method of determining tolerance to an agent in a healthy subject, comprising:
(a) determining a signature of a microbiome in a sample of the healthy subject who has been subjected to the agent or condition; and (b) comparing said signature of said microbiome of the healthy subject to at least one reference signature of a pathological microbiome, wherein when said signature of the microbiome of the healthy subject is statistically significantly similar to said reference signature of said pathological microbiome, it is indicative that the healthy subject is intolerant to the agent.

2 . A method of determining an effect of an agent on a microbiome of a healthy subject comprising:
(a) exposing the microbiome to the agent; (b) comparing the signature of said microbiome following said exposing with a reference signature of a pathological microbiome, wherein when said signature of said microbiome is statistically significantly similar to said pathological microbiome reference signature, it is indicative that said agent has a deleterious effect on the microbiome.

3 . The method of claim 2 , further comprising comparing the signature of said microbiome following said exposing with a non-pathological microbiome reference signature, wherein when said signature of said microbiome is statistically significantly different to said non-pathological microbiome reference signature, it is indicative that said agent has a deleterious effect on the microbiome.

4 . The method of claim 2 , wherein said exposing is effected in vivo.

5 . The method of claim 1 , further comprising comparing said signature of said microbiome of the healthy subject to at least one non-pathological reference signature, wherein when said signature of said microbiome of the healthy subject is statistically significantly different to said at least one non-pathological reference signature, it is indicative that the healthy subject is intolerant to the agent.

6 . The method of claim 1 , wherein the agent is a substance.

7 . The method of claim 1 , wherein the agent is a condition.

8 . The method of claim 6 , wherein said substance is a food additive.

9 . The method of claim 8 , wherein said food additive is a preservative.

10 . The method of claim 8 , wherein said substance is an artificial sweetener.

11 . The method of claim 1 , wherein said pathological microbiome is derived from a healthy subject who is intolerant to the agent.

12 . The method of claim 3 , wherein said non-pathological microbiome is derived from a healthy subject who is tolerant to the agent.

13 . The method of claim 10 , wherein said artificial sweetener comprises a component selected from the group consisting of saccharin, steviol and Aspartame.

14 . The method of claim 1 , wherein said signature of a microbiome is a presence or level of microbes of said microbiome.

15 . The method of claim 1 , wherein said signature of a microbiome is a presence or level of genes of microbes of said microbiome.

16 . The method of claim 1 , wherein said signature of a microbiome is a product generated by microbes of said microbiome.

17 . The method of claim 16 , wherein said product is selected from the group consisting of a mRNA, a polypeptide, a carbohydrate and a metabolite.

18 . The method of claim 16 , wherein said product comprises short chain fatty acids (SCFAs).

19 . The method of claim 1 , further comprising subjecting the subject to the agent prior to the analyzing.

20 . The method of claim 1 , wherein data pertaining to said reference signature of a pathological microbiome is found on a first database and data pertaining to said signature of a microbiome of said healthy subject is found on a second database.

21 . The method of claim 20 , wherein said first database comprises data pertaining to a plurality of reference signatures of a pathological microbiome.

22 . A method of determining tolerance to an artificial sweetener in a healthy subject comprising analyzing the amount of a microbe belonging to an order selected from the group consisting of bacteroidales order, Clostridilales order, Bactobacillales order, YS2 order, RF32 order, Erysipelotrichales order, Burkholderiales order and/or Campylobacterales order in a microbiome of the subject, wherein an amount of microbes of the Bacteroidales, Clostridilales, Bactobacillales and/or YS2 order above a predetermined level is indicative of a subject being tolerant to the artificial sweetener and an amount of microbes of the RF32, Erysipelotrichales, Burkholderiales and/or Campylobacterales order above a predetermined level is indicative of a subject being intolerant to the artificial sweetener.

23 . A method of determining tolerance to an artificial sweetener in a healthy subject comprising analyzing the amount of at least one microbe or class of microbes as set forth in Table 5 in a microbiome of the subject, wherein the amount of at least one of said microbes or said class of microbes above a predetermined level is indicative of a subject being intolerant to the artificial sweetener.

24 . The method of claim 1 , wherein said microbiome is selected from the group consisting of a gut microbiome, an oral microbiome, a bronchial microbiome, a skin microbiome and a vaginal microbiome.

25 . The method of claim 1 , further comprising processing said sample prior to the determining.

26 . The method of claim 25 , wherein said processing comprises generating a nucleic acid sample.

27 . The method of claim 22 , further comprising administering the artificial sweetener to the subject prior to the analyzing.

28 . A method of restoring the tolerance of a subject to an agent comprising administering to the subject an effective amount of a probiotic composition which comprises statistically significantly similar microbes to the non-pathological microbiome, thereby restoring the subjects tolerance to the agent.

29 . The method of claim 28 , wherein said agent comprises a substance.

30 . The method of claim 28 , wherein said agent comprises a condition.

31 . The method of claim 30 , wherein said condition comprises circadian misalignment.

32 . The method of claim 28 , wherein said substance is a food additive.

33 . The method of claim 32 , wherein said food additive is a preservative.

34 . The method of claim 29 , wherein said substance is an artificial sweetener.

35 . A probiotic composition, wherein a majority of the microbes of the composition are microbes of the bacteroidales order, the Clostridilales order, the Bactobacillales order and/or the YS2 order, the composition being formulated for rectal or oral administration.

36 . A method of restoring the tolerance of a subject to an artificial sweetener comprising administering to the subject an effective amount of probiotic composition of claim 35 , thereby restoring the tolerance of the subject to the artificial sweetener.

37 . A method of restoring the tolerance of a subject to an artificial sweetener comprising administering to the subject an effective amount of antibiotic which reduces the relative abundance of a microbe being of the RF32, Erysipelotrichales, Burkholderiales and/or Campylobacterales order, thereby restoring

Assignees

• Yeda Res & Dev
• Yeda Res & Dev

Inventors

• Elinav Eran
• Segal Eran

Classifications

• C12Q1/025

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18) · CPC title

• A61K35/741 Primary

  Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06) · CPC title

• G01N2570/00

  Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes · CPC title

• C12Q1/04

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title