Abstract

Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Hypercaloric diets are tightly related to the obesity etiology and also cause alterations in gut microbiota functionality. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent an accurate strategy to understand its relationship with obesity caused by diet. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function. To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as a complementary obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption. This new approach could be implemented to support the dietary and healthy habits recommended as a first option to maintain the homeostasis of the microbiota.

Highlights

  • Obesity is defined as a disequilibrium in energy balance and is currently a global health problem in Western societies, where its prevalence has increased considerably in recent years

  • To assess the impact of diet on gut microbiota, metagenomics and metaproteomics analyses were performed in cecal samples obtained immediately after sacrifice that were divided into two equal portions for use in both omics approaches

  • The gut microbiota is essential for maintaining health and has a primary role in metabolism and homeostasis, and its alteration during high fat diet-induced obesity is a problem that needs to be addressed

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Summary

Introduction

Obesity is defined as a disequilibrium in energy balance and is currently a global health problem in Western societies, where its prevalence has increased considerably in recent years. It is widely known that obesity is affected by numerous factors, such as diet, lifestyle and genetic background [2], and recently it has been shown to be related to gut microbiota [3], which have been implicated in energy homeostasis and metabolic functions [4]. There are different obesogenic diets that can be employed. One example of these diets is the semi-purified high-fat diet [6,7]. These types of diets are more commonly used in these models due to their well-defined nutritional composition [8,9,10]

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