Type 2 diabetes – microbiome impacts insulin resistance
Six percent of the UK population suffers from type 2 diabetes (T2D), the yearly cost of patient treatments is some 12 billion £. T2D is a risk factor for chronic and incurable cardiovascular diseases (CVD), which are one of the main causes of mortality in developed countries, responsible for over 27% of UK deaths in 2013. Increased resistance to insulin, the hormone that controls glucose levels, is, in turn, a risk factor for T2D. Preventing or slowing down development of insulin resistance (IR) could lead to a decrease in costly, debilitating and mortal diseases. Individuals with IR have high blood levels of several essential amino-acids, collectively labelled branched chain amino-acids (BCAA; isoleucine, leucine and valine). It is thought that BCAA play a role in the development of IR, but it is not known what controls their serum levels – as our bodies can’t synthesise them, they must be provided by our food or our gut microbiome.
An international team including King’s College London has reported this week in Nature that the gut microbiome can impact the level of BCAA in the serum. Concomitant analysis of the gut microbiome composition, IR and over a thousand serum metabolites and lipids (the metabolome) in 272 non-diabetic individuals revealed that high IR individuals carry a microbiome that has increased capacity to produce BCAA and lowered capacity to utilise them. The most important bacterial species for BCAA production were two members of the Bacteroidetes family, Prevotella copri and Bacteroides vulgates. These are known to be mutually exclusive – individuals that have high levels of Bacteroides have low levels of Prevotella and vice versa, they belong to two different enterotypes that harbour distinct bacterial communities. Individuals with low levels of both bacteroides and prevotella harbour higher levels of two BCAA-utilising species, Butyrivibrio crossotus and Eubacterium siraeum.
The direct role of P. copri on BCAA levels and IR was shown in mice. Supplementing a high fat diet with P. copri increased both the BCAA and IR without significant alteration of the overall gut microbiome composition. Nevertheless, in humans, it is likely that the whole microbial community may play a role, even if some of its members appear more important than others. From a health-related perspective, the study opens avenues for targeting the microbiome to prevent, or at least slow down, development of IR and, in turn, deadly and incurable diseases.
Currently online, out on paper on the 20th of July.
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature18646.html