Outcomes from a Finnish trial show that indolepropionic acid, a secondary metabolite produced by gut bacteria, could prevent diabetes by protecting the insulin-producing function of beta-cells.
In addition, the team reported that lipid metabolites linked with type 2 diabetes (T2D) could boost insulin sensitivity.
“Earlier studies have linked intestinal bacteria with the risk of disease in overweight people,” said Kati Hanhineva, Academy Research Fellow at the University of Eastern Finland.
“Our findings suggest that indolepropionic acid may be one factor that mediates the protective effect of diet and intestinal bacteria.”
The findings directly associate indolepropionic acid production with dietary fibre intake, pointing to a strong link between diet, intestinal microbiota, insulin and glucose metabolism and T2D risk.
“This hypothesis fits well with previous observational findings on the protective role of fibre and low-fat high-complex carbohydrate diet for T2D,” the study put forward.
“The role of microbiota in e.g. efficient conversion of complex indigestible dietary carbohydrates into short-chain fatty acids and maintenance of gut microbiome carbohydrate fermentation seem to be important to maintain gut and systemic health.”
A metabolomics approach
The study consisted of two groups that were made up of 200 overweight participants with impaired glucose tolerance.
Blood metabolite profiles of these subjects were determined who either developed T2D within the first five years, or did not convert to T2D within a 15-year follow-up.
A metabolomics approach was taken in which concentrations of several metabolites, such as nutrient intermediates, lipids, hormones and other signalling molecules, could be determined.
Results identified a higher indolepropionic acid concentration was linked with a reduced risk of T2D developing.
In those who remained T2D free, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively.
The presence of these metabolites appeared to also suppress low-grade inflammation.
“Taken together, our results suggest that T2D is predicted by circulating metabolites reflecting gut microbiota composition and function,” the study concluded.
“The observed inverse relationship of low-grade inflammation with protective lipid metabolites and indolepropioinic acid support this view.”
METSIM and VIP
The findings from this study closely mimic those in two comparable studies, which also highlighted the protective role of indolepropionic acid.
In the METSIM (Metabolic Syndrome in Men) study, Finnish researchers also found during a 5-year follow-up that indolepropionic acid was lower in subjects who developed T2D than in those who remained non-diabetic.
The Swedish Västerbotten Intervention Program (VIP) found that indolepropionic acid was around 15% lower in T2D cases than in their matched healthy controls at baseline and was negatively associated with T2D incidence.
Despite the strength of all three findings, the researchers highlighted a few limitations that may have had a bearing on the results.
These include the use of samples collected one year after the onset of the study as baseline samples available at the start of the trial were not available.
Additionally, insulin secretion and insulin sensitivity were not measured either by the hyperinsulinaemic-euglycaemic clamp or the intravenous glucose tolerance test (IVGTT), a method considered the ‘gold standard’ of measuring insulin resistance.
Source: Nature Scientific Reports
Published online ahead of print: doi:10.1038/srep46337
“Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study.”
Authors: Vanessa de Mello et al.