Does a diverse microbiota lower the risk of diabetes?

Even though some studies had already made a link between the intestinal microbiota and type 2 diabetes (T2D), they were limited by a small sample size and there was ongoing debate as to the exact taxonomic units involved (results not always reproducible, insufficient power, etc.) This is why researchers decided to embark upon a large-scale study of 2,166 subjects taken from two Dutch cohorts, to investigate links between the composition of the intestinal microbiota (analyzed using bacterial 16S RNA gene sequencing and amplification on fecal samples) and T2D (verified by two physicians using WHO criteria (blood glucose, use of anti-diabetic drugs, etc.).

Even though it used a cross-sectional design (i.e., data about the microbiota and T2D collected at the same time), the analyses were adjusted for several confounders, such as energy intake, body mass index, education level, etc. Another strength and novel aspect of the study was the investigation of links between the microbiota and insulin resistance (IR), measured using fasting insulin and blood glucose, a significant subclinical parameter indicating an early stage in the pathogenesis of T2D.

Does a diverse microbiota strengthen protection?

Several indicators of microbiota α-diversity (sidenote: α diversity A measure indicating the diversity of a single sample, i.e. the number of different species present in an individual. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej200997 ) were linked to lower IR and a reduced prevalence of T2D. In turn, β-diversity (sidenote: β diversity A measure indicating the species diversity between samples, it allows to assess the variability of microbiota diversity between subjects. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej20099 ) was linked to IR. Finally, an abundance of seven taxonomic units - belonging to the Christensenellaceae and Ruminococcaceae families and the genus Marvinbryantia - were linked to a lower risk of IR, and an abundance of five other taxa - the Clostridiaceae and Peptostreptococcaceae families, and the genera Clostridium sensu stricto, Intestinibacter and Romboutsia – to a lower risk of T2D.

Butyrate-producing taxa that reduce the risk of T2D

These 12 taxonomic units, 10 of which have been linked for the first time to a lower risk of T2D or IR, are known to produce butyrate, a short-chain fatty acid produced by the breakdown of dietary fibers by bacteria. Enhanced mitochondrial activity, improved energy metabolism, and reduced endotoxemia and inflammation are some of the mechanisms put forward to explain these effects. However, ad hoc studies are still needed to validate its role in glucose metabolism and the prevention of diabetes.

Nevertheless, the links that have been identified between, on the one hand, microbiota diversity and an abundance of butyrate-producing bacteria, and on the other hand, a lower risk of IR and T2D, shed further light on the etiology, pathogenesis, and treatment of type 2 diabetes.