Dietary Non-Protein Nitrogen-Containing Compounds and the Microbiota-Gut-Liver Axis in Glycolipid Metabolism: Beneficial Effects and Mechanistic Insights

Disorders of glycolipid metabolism can predispose individuals to metabolic diseases, posing significant risks to human health. Dietary non-protein nitrogen-containing compounds (NPNCCs) not only supplement essential nitrogen but also ameliorate intestinal homeostasis to counteract metabolic dysregulation. In this review, food-derived NPNCCs are categorized into eight categories: alkaloids, amines and their derivatives, non-protein amino acids, vitamins, nitrogen-containing organic acids, nucleotides, alkaline polysaccharides, and nitrates. NPNCCs interact with the host gut microbiota and regulate glycolipid synthesis and decomposition, energy expenditure, and intestinal barrier integrity by reshaping the abundances of key microbial taxa such as Bifidobacterium, Lactobacillus, Bacteroides, Akkermansia, and Lachnospiraceae_NK4A136_group. Furthermore, NPNCCs influence host glycolipid metabolism through the microbial-gut-liver axis, involving neuroendocrine regulation, secretion of secondary metabolites, and modulation of the enterohepatic circulation. Among these, the FXR/FGF15/CYP7A1, TMA/FMO3/TMAO, and TGR5/GLP-1 pathways represent three major routes within the enterohepatic circulation. Finally, given the complexity and diversity of both NPNCCs and the gut microbiota, a comprehensive analysis of their association and the mechanism of regulating glycolipid metabolism still requires further research data and validation.