Microbiome-based diagnosis, prediction and treatment of relapsing obesity

Abstract

A method of analyzing the likelihood of weight regain in a subject who has reached a target weight by practicing a weight loss program is disclosed. The method comprises determining an amount or presence of at least one microbe and/or product thereof in the gut microbiome of the subject, wherein the amount of the at least one microbe is altered during a prior weight gain period of the subject to reach a level representative of an obese subject and further wherein the amount of the at least one microbe is retained at the level following the weight loss program, wherein the amount or presence of the at least one microbe or product thereof is predictive of weight regain.

1 . A method of analyzing the likelihood of weight regain in a subject who has reached a target weight by practicing a weight loss program, the method comprising determining an amount or presence of at least one microbe and/or product thereof in the gut microbiome of the subject, wherein the amount of said at least one microbe is altered during a prior weight gain period of the subject to reach a level representative of an obese subject and further wherein the amount of said at least one microbe is retained at said level following said weight loss program, wherein the amount or presence of said at least one microbe or product thereof is predictive of weight regain. 
     
     
         2 . A method of monitoring the efficacy of a dieting aid in a subject:
 (a) treating the subject with a dieting aid; and   (b) analyzing for the presence or the level of a microbe in the family Weeksellaceae and/or product thereof, a microbe in the family Tissierellaceae and/or a product thereof, a microbe in the genus  Lactobacillus  and/or a product thereof, a microbe in the genus  Bacteroides  and/or a product thereof, a microbe in the class Mollicutes and/or a product thereof, a microbe in the class Gammaproteobacteria and/or a product thereof, a microbe in the phylum Actinobacteria and/or a product thereof, a microbe in the phylum Tenericutes and/or a product thereof, a microbe in the species  Bacteroides acidifaciens  and/or a product thereof, and a microbe in the species  Bacteroides uniformis  and/or a product thereof;   wherein the level or presence of at least one of said microbes or product thereof is indicative of the efficacy of a dieting aid.   
     
     
         3 . The method of  claim 1 , wherein said at least one microbe is differentially present in the gut microbiome of the subject as compared with in the gut microbiome of a non-obese control who has not undergone a weight loss program. 
     
     
         4 . The method of  claim 1 , wherein said product thereof is a metabolite. 
     
     
         5 . The method of  claim 1 , wherein the subject who has reached a target weight has terminated said weight loss program. 
     
     
         6 . The method of  claim 1 , wherein said analyzing is effected in a fecal sample of the subject. 
     
     
         7 . The method of  claim 1 , wherein said at least one microbe is in the family Weeksellaceae or Tissierellaceae, in the genus  Lactobacillus  or  Bacteroides , in the class Mollicutes or Gammaproteobacteria, in the phylum Actinobacteria or Tenericutes or in the species  Bacteroides acidifaciens  or  Bacteroides uniformis.    
     
     
         8 . A method of reducing the risk of weight gain in a subject who has reached a target weight by practicing a weight loss program, the method comprising administering to the subject an agent which alters the gut microbiome of the subject so that a signature of said gut microbiome becomes more similar to a signature of a gut microbiome of a non-obese subject who has not undergone a weight loss program, thereby reducing weight gain in the subject. 
     
     
         9 . The method of  claim 8 , wherein the signature of said gut microbiome comprises a microbe diversity. 
     
     
         10 . The method of  claim 8 , wherein said agent is a fecal transplant of a healthy subject who has not undergone a weight loss program. 
     
     
         11 . The method of  claim 8 , wherein said signature of said gut microbiome is a metabolite signature. 
     
     
         12 . The method of  claim 8 , wherein said signature of said gut microbiome is a bacterial signature. 
     
     
         13 . The method of  claim 8 , wherein said agent downregulates at least one metabolite selected from the group consisting of ursodeoxycholate, glycocholate, phenylacetate and heptanoate. 
     
     
         14 . The method of  claim 8 , wherein said agent is a flavonoid. 
     
     
         15 . The method of  claim 14 , wherein said flavonoid is apigenin and/or naringenin. 
     
     
         16 . The method of  claim 8 , wherein said agent is a probiotic. 
     
     
         17 . The method of  claim 16 , wherein said probiotic is a bacterial population associated with nitrate synthesis or heptose biosynthesis. 
     
     
         18 . The method of  claim 8 , wherein said agent is an antibiotic. 
     
     
         19 . The method of  claim 18 , wherein said antibiotic agent downregulates an amount and/or activity of the class Mollicutes or of the order Bacteroidales. 
     
     
         20 . The method of  claim 8 , further comprising analyzing said signature of said gut microbiome of the subject prior to the administering. 
     
     
         21 . The method of  claim 8 , wherein the subject who has reached a target weight has terminated said weight loss program. 
     
     
         22 . The method of  claim 2 , wherein said product thereof is a metabolite. 
     
     
         23 . The method of  claim 2 , wherein said analyzing is effected in a fecal sample of the subject.