Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates that Clostridiales and Enterococcus could play a key role in the disease

Abstract

There is growing evidence indicating that gut microbiota contributes to the development of metabolic syndrome and Type 2 Diabetes (T2D). The most widely-used model for T2D research is the leptin deficient db/db mouse model. Yet, a characterisation of the gut microbial composition in this model in relationship with the metabolism is lacking. The objectives of this study were to identify metabolomics and microbial modulations associated with T2D in the db/db mouse model. The majority of microbial changes observed included an increase of Enterobacteriaceae and a decrease of Clostridiales in diabetics. The metabolomics interrogation of caecum indicated a lower proteolytic activity in diabetics, who also showed higher Short-Chain Fatty Acid (SCFA) levels. In the case of faeces, the model identified 9 metabolites, the main ones were acetate, butyrate and Branched Chain Amino Acids (BCAAs). Finally, liver was the organ with more metabolic links with gut-microbiota followed by the Gut-Brain Axis (GBA). In conclusion, the interaction between Clostridiales and Enterococcus with caecal metabolism could play a key role in the onset and development of diabetes. Further studies should investigate whether the role of these bacteria is causal or co-occurring.