Dietary and host-derived metabolites in the gut lumen

Dietary and host-derived metabolites in the gut lumen represent the diverse array of small molecules present within the gastrointestinal tract, originating from food intake, host secretions, and microbial transformation (Nicholson et al., 2012, Nature). This complex metabolome includes short-chain fatty acids (SCFAs) like butyrate, bile acids, amino acid derivatives such as indoles, and lipids, which serve as critical signaling molecules between the microbiota and the host (Koh et al., 2016, Cell). These metabolites interact with various host receptors, including G protein-coupled receptors (e.g., GPR41, GPR43) and nuclear receptors (e.g., FXR, PXR, AhR), to regulate immune responses, energy metabolism, and intestinal barrier integrity (Fan & Pedersen, 2021, Nature Reviews Microbiology). Dysregulation of this metabolite pool is strongly linked to the pathogenesis of inflammatory bowel disease (IBD), obesity, and metabolic syndrome (Postler & Ghosh, 2017, Cell Host & Microbe). While not a single therapeutic target, the gut metabolome is a focal point for drug development, with strategies aiming to modulate metabolite levels through diet, probiotics, or small molecule drugs to restore homeostasis and treat systemic diseases.

Other names

Gut metabolomeIntestinal metabolitesLuminal metabolitesMicrobiota-derived metabolitesGastrointestinal metabolite pool

Modulation of the gut chemical environment through sequestration of harmful metabolites, altered microbial production via antibiotics or biotics, or direct supplementation of beneficial metabolites to activate host receptors such as GPCRs and nuclear receptors.