A Scoping Review: Metabolomics Signatures Associated with Animal and Plant Protein Intake and Their Potential Relation with Cardiometabolic Risk

ABSTRACT The dietary shift from animal protein (AP) to plant protein (PP) sources is encouraged for both environmental and health reasons. For instance, PPs are associated with lower cardiovascular and diabetes risks compared with APs, although the underlying mechanisms mostly remain unknown. Metabolomics is a valuable tool for globally and mechanistically characterizing the impact of AP and PP intake, given its unique ability to provide integrated signatures and specific biomarkers of metabolic effects through a comprehensive snapshot of metabolic status. This scoping review is aimed at gathering and analyzing the available metabolomics data associated with PP- and AP-rich diets, and discusses the metabolic effects underlying these metabolomics signatures and their potential implication for cardiometabolic health. We selected 24 human studies comparing the urine, plasma, or serum metabolomes associated with diets with contrasted AP and PP intakes. Among the 439 metabolites reported in those studies as able to discriminate AP- and PP-rich diets, 46 were considered to provide a robust level of evidence, according to a scoring system, especially amino acids (AAs) and AA-related products. Branched-chain amino acids, aromatic amino acids (AAAs), glutamate, short-chain acylcarnitines, and trimethylamine-N-oxide, which are known to be related to an increased cardiometabolic risk, were associated with AP-rich diets, whereas glycine (rather related to a reduced risk) was associated with PP-rich diets. Tricarboxylic acid (TCA) cycle intermediates and products from gut microbiota AAA degradation were also often reported, but the direction of their associations differed across studies. Overall, AP- and PP-rich diets result in different metabolomics signatures, with several metabolites being plausible candidates to explain some of their differential associations with cardiometabolic risk. Additional studies specifically focusing on protein type, with rigorous intake control, are needed to better characterize the associated metabolic phenotypes and understand how they could mediate differential AP and PP effects on cardiometabolic risk.