Heritable components of the human fecal microbiome are associated with visceral fat

Abstract

Obesity and its associated diseases are one of the major causes of death worldwide. The gut microbiota has been identified to have essential regulatory effects on human metabolism and obesity in particular. In a recent study we provided some insights into the link between the gut microbiota (GM) and adiposity, as well as host genetic modulation of these processes. Our results identify novel evidence of association between 6 adiposity phenotypes and faecal microbial operational taxonomic units (OTUs). Accumulation of visceral fat, a key risk factor for cardio-metabolic disease, has the strongest and most pervasive signature on the gut microbiota of the factors we examined. Furthermore, we observe that the adiposity-associated OTUs were classified as heritable and in some cases were also associated with host genetic variation at obesity-associated human candidate genes FHIT, TDRG1 and ELAVL4. This addendum confirms our previously published results in the TwinsUK cohort using a different approach to OTU clustering and multivariate analysis, and discusses further the importance of considering the GM as a complex ecosystem.

Keywords: gut microbiome; heritability; obesity; visceral fat mass.

Figure 1.

VFM is strongly associated with gut microbiota composition. A. VFM distribution within the extended TwinsUK data set (n = 1313). B. Plot of the observed scores against the cross-validated scores generated by the O-PLS DA calculated using VFM as a predictor and 155 OTUs (belonging to the Bacteroides, Clostridium, Blautia, Coprococcus, Lachnospira, Oscillospira and Ruminococcus genera) relative abundance as a matrix of independent responders, each score represents one of the 1313 individuals used to generate the model and is color-coded in accordance to individual VFM level. C. Diversity distribution of the 155 OTUs used to generate the O-PLS DA model and of the 26 OTUs that were considered as significantly associated to VFM from the same model. D. Association loadings between VFM and the 14 significant OTUs; genera highlighted in blue are OTUs that were negatively associated with VFM in the Beaumont et al paper, while those in red are positively associated, and purple represents a mixture of positive and negative associations.