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

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Schematic representation of the experimental design.

LFD, Low-Fat Diet; HFD, High-Fat Diet; ABS, Antibiotics; FMT, Fecal Microbiota Transplantation.

Fig 2

A) Measurement of body weight during the 14 weeks of study and B) the percentage of body fat measured at weeks 1, 9, 11 and 14. *p

Fig 3

A) PCA of the family OTU abundance and the proteins that were identified that shows the separation between the LFD and HFD groups. The first two components are shown along with the percent variance that is explained by each. The points correspond to the individual samples.

Fig 4

A) Differences in the actual OTU abundances among the different groups at the phylum taxon levels. B) PCA of the differences between the groups treated with and without ABS. The first two components are shown along with the percentages of variance that they explain. The points correspond to individual samples.

Fig 5

A) PCA of OTU abundance. The first two components are shown along with the percentage of variance that they explain. The points correspond to individual samples. B) Hierarchical clustering analysis of the three significant families in the LFD, HFD and FMT groups.

Fig 6

A) PCA of up- and downregulated proteins showing the separation between the three groups. The first two components are shown along with the percentages of variance that they explain. The points correspond to individual samples. B) Percentages of proteins that represent the 15 most abundant protein functions according to Gene Ontology (GO) terms in the LFD, HFD and FMT groups. C) Hierarchical clustering analysis of 21 significant proteins in the LFD, HFD and FMT groups.

Fig 7. Significant correlations between families and proteins in the LFD, HFD and FMT groups.