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.

Metabolomics signatures of plant protein intake: effects of amino acids and compounds associated with plant protein on cardiometabolic health

“…PP are lower in essential AA (particularly methionine, lysine, and tryptophan) but provide higher amounts of arginine, glycine, alanine, and serine (nonessential AA). In contrast, branched chain AAs (BCAAs: leucine, isoleucine and valine) and aromatic AA (AAA: tyrosine and phenylalanine) are present in higher quantities in AP [17 ▪▪ ]. Thus, distinct plasma untargeted metabolomic profiles are associated with intakes from animal and plant protein sources [22 ▪▪ ].…”

“…The effects of AP and PP may therefore be mediated through complex combinations of macro and micronutrients, affecting numerous metabolic pathways, thus constituting the substrates and mechanisms of their effects on cardiometabolic health. Given the multitude of pathways potentially involved, the use of holistic and integrative approaches, such as metabolomics, has emerged as the most relevant to characterize the effects of AP and PP [17 ▪▪ ]. By profiling the global signature (metabolome) of an individual, it is possible to obtain a snapshot of metabolic status.…”

“…Though several hypotheses have been proposed, the mechanistic bases for the effects of AP and PP on cardiometabolic health are still largely unknown. In recent years, several studies reported metabolomics signatures related to the nutritional protein transition and provided novel hypotheses leading to a better understanding of the molecular processes involved in relation to prevention of cardiometabolic diseases [17 ▪▪ ]. In this review, we focus on the metabolomics signatures associated with diets contrasting in their protein sources, going beyond the specific protein nature and AA composition.…”

Plasma Metabolite Profiles Following Consumption of Animal Protein and Soybean-Based Diet in Hypercholesterolemic Postmenopausal Women

“…Plasma metabolites in a cohort living in Japan found that hydroxyproline, 3-methylhistidine, aromatic amino acids, beta-alanine, carnitine and 2-aminobutyrate were positively associated with animal protein intake [ 11 ]. These studies identified different clusters of animal protein associated metabolites [ 4 , 9 , 10 , 11 ], with amino acids being the main metabolites that differed between dietary animal and plant proteins [ 12 ].…”

Plant to animal protein ratio in the diet: nutrient adequacy, long-term health and environmental pressure

“…However, plant proteins are also important for the intake of some indispensable nutrients and fiber, and are also lower in saturated fats (5). Beyond the relationship to nutrient adequacy, animal/plant proteins and their packages largely affect the metabolome and the microbiota and physiological functions that are crucial for long-term health (5)(6)(7)(8). Accordingly, there have been many contrasting associations reported recently between plant and animal protein intake and mortality, especially regarding cardiovascular diseases (5,9,10).…”