Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes
Ilias Attaye, Pierre Bel Lassen, Solia Adriouch, Emilie Steinbach, Rafael Patiño‐Navarrete, Mark Davids, Rohia Alili, Flavien Jacques, Sara Benzeguir, Eugeni Belda, Ina Nemet, James T. Anderson, Laure Alexandre‐Heymann, Arno Greyling, Étienne Larger, Stanley L. Hazen, Sophie L. van Oppenraaij, Valentina Tremaroli, Katharina R. Beck, Per-Olof Bergh, Fredrik Bäckhed, Suzan P.M. ten Brincke, Hilde Herrema, Albert K. Groen, Sara‐Joan Pinto‐Sietsma, Karine Clément, Max Nieuwdorp
Abstract
High-protein diets are promoted for individuals with type 2 diabetes (T2D). However, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized-controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and -derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure.