Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases

Abstract

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

Keywords: High-fat diets; chronic diseases; gut microbiota; metabolites.

Figure 1.

Effects of HFD on gut microbiota dysbiosis.

Figure 2.

HFD-induced gut microbiota disturbances are associated with common chronic metabolic diseases.

Figure 3.

Microbial metabolites associated with HFD regulate host metabolism. An overview of HFD-induced changes in gut microbial metabolic responses affecting host energy homeostasis, body fat, inflammation, glucose regulation, insulin sensitivity, and hormone secretion. SCFAs: short chain fatty acids. LPS: lipopolysaccharide. BCAA: branched-chain amino acid. IAA: indole-3-acetic acid. IPA: indole-3-propionic acid. 5-HIAA: 5-hydroxyindole-3- acetic acid. 5-HT: 5-hydroxytryptamine. PGN: peptidoglycan. TMA: trimethylamine. GPCRs: G protein-coupled receptors. TLR: toll-like receptor. GLP-1: glucagon-like peptide-1. PYY: peptide YY. AhR: aryl hydrocarbon receptor. TMAO: trimethylamine oxide. TJps: tight junction proteins. FIAF: fasting-induced adipokine. Ecs: endocannabinoid systems. UCP1: uncoupling protein-1.