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Microbiome-based diagnosis, prediction and treatment of relapsing obesity

Inactive Publication Date: 2019-05-16
YEDA RES & DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for reducing the risk of weight gain in individuals who have reached their target weight through a weight loss program. This is achieved by administering a therapeutically effective amount of an agent that modulates the gut microbiome, either up-regulating or down-regulating certain microbes or products that were previously associated with weight gain or weight loss during the weight loss process. This method helps to maintain the gut microbiome signature of non-obese individuals who have not undergone a weight loss program, reducing the risk of weight gain in the individual.

Problems solved by technology

Collectively, the global obesity endemic has far-reaching consequences on life expectancy, quality of life, and healthcare costs.
Despite a continuous worldwide medical and scientific effort, no medical intervention to date has been consistently shown to have long-lasting effects in reversing the obesity epidemic.
A plethora of dietary approaches have been claimed to efficiently induce a significant weight reducing effects, yet the vast majority of these have proven to be non-efficacious over prolonged period of time, or incompatible with long-term compliance.
Moreover, in more than 80% of cases in which weight loss was initially successful, the reduced weight is not maintained, and instead followed by recurrent weight gain and relapsing metabolic complications within 12 months of initial weight reduction that exceeded the pre-dieting metabolic derangements.

Method used

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  • Microbiome-based diagnosis, prediction and treatment of relapsing obesity
  • Microbiome-based diagnosis, prediction and treatment of relapsing obesity
  • Microbiome-based diagnosis, prediction and treatment of relapsing obesity

Examples

Experimental program
Comparison scheme
Effect test

example 1

Enhanced Recurrent Weight gain after Treatment of Obesity

[0278]To study the mechanisms underlying post-dieting weight gain, a mouse model of relapsing obesity was used, in which mice were exposed to cycles of high-fat diet (HFD) feeding, intermitted by normal chow (NC) consumption (cycHFD). Consequently, in these mice, weight gain and features of the metabolic syndrome developed during exposure to HFD, followed by recuperation and weight reduction during exposure to NC, ensuing by a second cycle of HFD and associated metabolic derangements. As controls, mice continuously fed a HFD, mice continuously fed an NC diet and mice which were exposed to only a single cycle of HFD (primHFD) were used (FIG. 1A). As observed in recurrently dieting humans (3), a preceding obesity-weight loss cycle rendered mice susceptible to accelerated and enhanced secondary weight gain, even after fully returning to baseline weight (FIG. 1B). This relapsing obesity was characterized by an increase in total bo...

example 2

Persistence of a Memory-like Microbiome Signature after Weight loss

[0281]Since secondary weight gain was associated with enhanced metabolic derangements despite a full return to normal weight, it was hypothesized that initial obesity had caused persistent abnormalities that predisposed mice to relapsing metabolic disease upon re-feeding with HFD. The present inventors therefore performed metabolic profiling at the nadir phase, i.e. when previously obese mice had returned to their original weight. However, despite marked metabolic derangements during the obese phase, body fat content, glucose tolerance, and serum insulin levels were indistinguishable between post-dieting mice and their non-cycling controls (FIGS. 2A-D). Similarly, other hallmarks of obesity, such as physical activity, food and drink intake, oxygen consumption, energy expenditure, serum levels of leptin, and adipose tissue inflammation all returned to normal levels upon weight loss. In contrast, the composition of the...

example 3

The Persistent Altered Microbiome Drives Exaggerated Recurrent Weight gain

[0284]The present inventors next sought to investigate whether the post-obesity microbiome signature was causally involved in the metabolic complications associated with relapsing weight gain.

[0285]To this end, following a HFD consumption period, mice were treated with broad-spectrum antibiotics (vancomycin, neomycin, ampicillin, and metronidazole) during the following weight loss period (FIG. 3A). Notably, antibiotic treatment during dieting abolished the persistence of a post-obesity microbiome signature upon return to normal weight, as determined by 16S sequencing, and equilibrated the microbiota composition between previously obese mice and constantly lean controls (FIG. 3B). Remarkably, antibiotic treatment also abrogated the exacerbation of metabolic derangements upon weight regain, including body fat content and glucose intolerance, while control mice without antibiotics that were included in the same e...

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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.

Description

FIELD AND BACKGROUND OF THE INVENTION[0001]The present invention, in some embodiments thereof, relates to microbiome based methods of maintaining a target body weight and analyzing the likelihood of weight regain following a diet.[0002]The past century has witnessed an alarming increase in the prevalence of obesity, with currently more than 44% of the adult world population estimated to be overweight, and over 300 million adults suffering from morbid obesity. In addition to its epidemic proportions, obesity is considered a major risk factor for a number of closely associated diseases, including type II diabetes mellitus affecting close to 500 million people worldwide, non-alcoholic fatty liver disease emerging as the most common liver disease in the developed world, and ischemic cardiovascular disease considered the leading cause of overall mortality. Collectively, the global obesity endemic has far-reaching consequences on life expectancy, quality of life, and healthcare costs.[000...

Claims

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Application Information

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IPC IPC(8): A61K35/741A23L33/135A23L33/105A23L33/00A61K31/352C12Q1/689A61P3/04
CPCA23V2200/332A61K31/352A61K35/741A23L33/135A23V2002/00A23L33/30A23V2250/2116C12Q1/689A61P3/04A23L33/105A61K35/74C12Q1/02
Inventor ELINAV, ERANSEGAL, ERAN
Owner YEDA RES & DEV CO LTD
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