Research Article: Effects from diet-induced gut microbiota dysbiosis and obesity can be ameliorated by fecal microbiota transplantation: A multiomics approach

Date Published: September 23, 2019

Publisher: Public Library of Science

Author(s): Maria Guirro, Andrea Costa, Andreu Gual-Grau, Pol Herrero, Helena Torrell, Núria Canela, Lluis Arola, Pratibha V. Nerurkar.


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.

Partial Text

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. Obesity triggers a vast number of comorbidities associated with hypertension, cardiovascular disease, and diabetes, as well as other conditions [1]. 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]. Moreover, the same factors that affect obesity can modulate gut microbiota composition, and the function of the gut microbiota will be affected by factors involved in gut microbiota-host equilibrium [5].

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. Our results applied a combination of metagenomics and metaproteomics approaches to confirm some previous observations: (i) the diet can alter the biochemical composition of the gut microbiota either by shifting the phenotype composition or the activity of bacterial cells; (ii) antibiotics disrupt microbiota biodiversity; (iii) FMT is effective in recolonizing the gut microbiota and in restoring some metabolic functions. When testing these three microbiota modulation strategies, different changes were observed in the bacterial metaproteome, demonstrating that every single change in the host environment can affect microbiota function. In addition to results observed over a short-term period of time [16,18], these findings show that a HFD has a major impact on the mouse cecal microbiota that extends beyond compositional changes to major alterations in bacterial physiology. Additionally, FMT can be considered as a new strategy to complement the conventional treatments for obesity based on healthy dietary and behavioral factors.