(LB04-02-26) Plant Protein–Dominant Diet Improves Glycaemic Variability and Reshapes Host–Microbiota Metabolism in Overweight Adults

Objectives: Dietary protein source has been associated with cardiometabolic health, yet its effects on glycaemic dynamics and gut microbiota–associated metabolism under controlled dietary conditions remain incompletely understood. To compare the metabolic effects of plant protein–dominant and animal protein–dominant diets on glycaemic variability and host–microbiota metabolic responses in overweight adults.

Methods: In a randomized, isocaloric, and isonitrogenous controlled feeding trial, 96 overweight adults were assigned to either a plant protein–dominant diet (PPD) or an animal protein–dominant diet (APD) for 3 weeks. All intervention diets were chemically validated to ensure precise nutrient exposure. Continuous glucose monitoring (CGM), shotgun metagenomics, plasma metabolomics, and fecal metabolomics were performed before and after intervention.

Results: Compared with APD, PPD resulted in greater reductions in CGM-derived glycaemic variability, accompanied by modest improvements in fasting glucose, lipid profiles, and renal indices despite comparable weight loss. Metagenomic analyses revealed selective remodeling of gut microbial functional profiles, with enrichment of fermentative taxa and suppression of Enterobacteriaceae-related signatures under PPD. Plasma metabolomics demonstrated distinct diet-associated metabolic patterns, including alterations in amino acid–related and plant-derived metabolites. Integrated multi-omics analyses identified coordinated associations among microbial functional modules, circulating metabolites, and glycaemic phenotypes.

Conclusions: Under controlled dietary conditions, dietary protein source differentially modulated glycaemic dynamics and host–microbiota metabolic profiles independent of energy intake and total protein quantity. These findings support a role for dietary protein quality in shaping metabolic regulation and glycaemic stability in humans.

Funding Sources: National Natural Science Foundation of China