Dietary protein intake and type 2 diabetes

The microbial composition of the gut microbiota affects human health and disease and plays a role in individuals with type 2 diabetes (T2D). Dietary composition is one of the most important factors shaping the gut microbiota. Furthermore, gut derived metabolite levels are potentially altered in T2D individuals depending on the dietary intake. So far, mainly microbial metabolism of dietary fibers has been studied, with less emphasis on dietary proteins. It is not known if and how dietary protein intake affects glucose and lipid metabolism in T2D.

MICRODIET (Understand and prevent production of microbially-produced pro-diabetic metabolites in different ethnic group: impact of dietary change’) was one of the projects granted under the HDHL-INTIMIC call co-funded by the European Commission that studied dietary protein intake in relation to the microbiota composition in T2D. Researchers from Sweden, France, and the Netherlands were involved in the project.

Aim

The aim of MICRODIET was to investigate how existing metagenome data available from different ethnicities is associated with different dietary patterns and to test how they respond to different dietary protein levels.

By using existing large patient cohorts, the consortium studied if there are correlations between dietary intake, gut microbiota composition and presence of obesity, insulin resistance and T2D. Moreover, the project tested the effect of 3 months dietary intervention of high protein (including animal and plant proteins) versus low protein on plasma (histidine) metabolites, glucose metabolism and gut microbiota composition in obese patients of different ethnic descent (Caribbean or Caucasian). Furthermore, they tested if these changes are driven by specific gut microbial strains and/or plasma metabolites using bioreactors.

Overall, they focused on whether a low-protein diet improves metabolism, alters the microbiota and reduces diabetogenic metabolites such as Imidazole Propionate (ImP) in T2D patients of different ethnicities. Lastly, they wanted to confirm if the microbiome produces ImP in humans using isotope-labelled histidine. The project also aimed to address whether the microbiota from healthy subjects and from patients with T2D differently metabolize aromatic amino acids, including histidine.

Results

There was no significant association found in the cohort study between protein intake (total, animal, or plant) with either gut microbiota diversity, regardless of ethnicity, but daily intake of (animal) protein was associated with glucose and lipid metabolism and T2D, which was independent of ethnic background. The results of the intervention trial did not show a clear effect on weight and glucose metabolism, but the researchers did observe a clear effect on plasma metabolites like phenylacetylglutamine.

The researchers of the MICRODIET project found that individuals with prediabetes or T2D have an altered microbiota that produce increased levels of ImP, which is confirmed in patients with different ethnicities. Dietary intake of protein (high versus low intake) had low effect on ImP levels. Nevertheless, they identified that diet, including animal protein, is associated with a small but significant effect on gut microbiota composition. The gut microbiota in T2D processes histidine in a different way, which may contribute to diabetes development both in subjects with a Caucasian or Caribbean background. 

The Dutch partner in the consortium has developed an online dietary tool that will help people to gain more insight into the relationship between (protein) diet, microbiota composition and metabolism and could potentially drive better treatment of DM2. The consortium is planning to run an implementation trial with the online tool to develop a ‘diet app’.

To summarize, the project found that dietary protein intake has no major impact on gut microbiota composition and production of bioactive metabolites is determined by both microbial composition, chemical environment, and substrate availability. Exploring this interaction more closely may provide increased understanding for how gut microbiota affects protein metabolism and production of bioactive amino acid derived metabolites.

In total, 11 projects were funded within the HDHL-INTIMIC cofunded call. All results will be shared on our website. Stay tuned! See ‘more information’ below for already published project results.

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