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; Etienne Larger; Stanley L Hazen; Sophie L van Oppenraaij; Valentina Tremaroli; Katharina Beck; Per-Olof Bergh; Fredrik Bäckhed; Suzan P M Ten Brincke; Hilde Herrema; Albert K Groen; Sara-Joan Pinto-Sietsma; Karine Clément; Max Nieuwdorp

doi:10.1016/j.isci.2023.107471

Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes

iScience. 2023 Jul 25;26(8):107471. doi: 10.1016/j.isci.2023.107471. eCollection 2023 Aug 18.

Authors

Ilias Attaye¹, Pierre Bel Lassen^{2

3}, Solia Adriouch², Emilie Steinbach², Rafael Patiño-Navarrete², Mark Davids¹, Rohia Alili², Flavien Jacques², Sara Benzeguir², Eugeni Belda², Ina Nemet^{4

5}, James T Anderson^{4

5}, Laure Alexandre-Heymann⁶, Arno Greyling⁷, Etienne Larger³, Stanley L Hazen^{4

5

8}, Sophie L van Oppenraaij¹, Valentina Tremaroli⁹, Katharina Beck⁹, Per-Olof Bergh⁹, Fredrik Bäckhed^{9

10}, Suzan P M Ten Brincke¹, Hilde Herrema¹, Albert K Groen¹, Sara-Joan Pinto-Sietsma¹, Karine Clément^{2

3}, Max Nieuwdorp¹

Affiliations

¹ Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands.
² Sorbonne Université, INSERM, Nutrition and Obesities; Systemic Approaches (NutriOmics), Paris, France.
³ Assistance Publique Hôpitaux de Paris, Pitie-Salpêtrière Hospital, Nutrition Department, Paris, France.
⁴ Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland, OH, USA.
⁵ Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH, USA.
⁶ Assistance Publique Hôpitaux de Paris, Cochin Hospital, Diabetes department, Paris, France.
⁷ Unilever Foods Innovation Centre, Wageningen, the Netherlands.
⁸ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland, OH, USA.
⁹ Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, 413 45 Gothenburg, Sweden.
¹⁰ Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden.

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.

Keywords: Dietary supplement; Health sciences; Human metabolism; Microbiome.