TY - JOUR
T1 - Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes
AU - Attaye, Ilias
AU - Lassen, Pierre Bel
AU - Adriouch, Solia
AU - Steinbach, Emilie
AU - Patiño-Navarrete, Rafael
AU - Davids, Mark
AU - Alili, Rohia
AU - Jacques, Flavien
AU - Benzeguir, Sara
AU - Belda, Eugeni
AU - Nemet, Ina
AU - Anderson, James T.
AU - Alexandre-Heymann, Laure
AU - Greyling, Arno
AU - Larger, Etienne
AU - Hazen, Stanley L.
AU - van Oppenraaij, Sophie L.
AU - Tremaroli, Valentina
AU - Beck, Katharina
AU - Bergh, Per-Olof
AU - Bäckhed, Fredrik
AU - ten Brincke, Suzan P. M.
AU - Herrema, Hilde
AU - Groen, Albert K.
AU - Pinto-Sietsma, Sara-Joan
AU - Clément, Karine
AU - Nieuwdorp, Max
N1 - Funding Information:
I.A. and P.B.L. were supported by a JPI HDHL MICRODIET grant (5290510105). I.A. was also supported by a Fullbright Scholarship (2021). M.N. is supported by a personal ZONMW-VICI grant 2020 [09150182010020]. M.N. K.C. F.B. and S.L.H. are supported by a Leducq consortium grant (fre). K.C. is supported by grants to the French Foundation of Medical research. K.C. and S.A. are also supported by National Agency of Research (ANR, deepIntegromics). E.S. is funded by Ministry of Research (MENRT grant). H.H. is supported by a Senior Fellowship of the Dutch Diabetes Research Foundation (no. 2019.82.004). Supports were also provided by Unilever, the Netherlands, and Nutrisens (Marion Leconte and Cyril Gratadou), France and K santé (Mr Vincent Guillet), France which provided food products in a collaborative program with APHP. Trial registration number: NCT03732690 (Paris) and NTR7424 (Amsterdam). I.A. P.B.L. K.C. and M.N. coordinated the clinical trial and drafted the first version of the manuscript. S.A. and S.L.O. coordinated the dietary adherence. R.P.N. V.T. and M.D. performed the metagenamic analysis. I.N. S.L.H. P.O.B. K.B. and F.B. coordinated the metabolomics analyses and integration in the study. I.A. also performed metabolomics analysis with the help of a Fulbright Scholarhip (2021). E.S. R.A. F.V. S.B. E.B. J.T.A. L.A.H. A.G. E.L. S.P.M.B. H.H. A.K.G. and S.J.P.S. helped with drafting the manuscript and provided input in the trial design and analyses. M.N. is in the SAB of Caelus health; however, this is not relevant for the current paper. S.L.H. reports being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, being a paid consultant formerly for Procter & Gamble in the past, and currently with Zehna Therapeutics, and both receiving research funds from Procter & Gamble, Zehna Therapeutics, and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Procter & Gamble, Zehna Therapeutics, and Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics.
Funding Information:
I.A. and P.B.L. were supported by a JPI HDHL MICRODIET grant ( 5290510105 ). I.A. was also supported by a Fullbright Scholarship (2021). M.N. is supported by a personal ZONMW-VICI grant 2020 [ 09150182010020 ]. M.N., K.C., F.B., and S.L.H. are supported by a Leducq consortium grant (fre). K.C. is supported by grants to the French Foundation of Medical research . K.C. and S.A. are also supported by National Agency of Research (ANR, deepIntegromics). E.S. is funded by Ministry of Research (MENRT grant). H.H. is supported by a Senior Fellowship of the Dutch Diabetes Research Foundation (no. 2019.82.004 ). Supports were also provided by Unilever, the Netherlands , and Nutrisens (Marion Leconte and Cyril Gratadou), France and K santé (Mr Vincent Guillet), France which provided food products in a collaborative program with APHP.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/8/18
Y1 - 2023/8/18
N2 - 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.
AB - 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.
KW - Dietary supplement
KW - Health sciences
KW - Human metabolism
KW - Microbiome
UR - https://www.scopus.com/pages/publications/85166940536
U2 - 10.1016/j.isci.2023.107471
DO - 10.1016/j.isci.2023.107471
M3 - Article
C2 - 37599833
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 8
M1 - 107471
ER -
SDG 3 Good Health and Well-being