Figure 1.

Diet-derived metabolites (red text) can alter multiple biologic pathways underlying diverse gastrointestinal (GI) diseases. (a) Dietary protein, both meat and nonmeat (e.g., grains, seeds, and nuts), includes varying levels of amino acids, such as tryptophan. Tryptophan can be metabolized by the host to produce kynurenines and serotonin (5-HT), which can alter gut physiology through the modulation of Toll-like receptors (TLRs) and serotonin receptors (5-HTRs), respectively. A small amount of tryptophan typically enters the colon, where it is synthesized by gut microbes. Gut microbiota can convert tryptophan to tryptamine or indole and indole derivatives via different metabolic pathways. Tryptamine increases intestinal secretion and mucus release from goblet cells by activating serotonin receptor 4 (5-HT₄R), while indole and indole derivatives are ligands for aryl hydrocarbon receptor (AHR) and play an important role in regulating barrier function and immune responses. (b) Dietary fiber includes both fermentable [e.g., fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), and inulin] and nonfermentable (e.g., cellulose, hemicellulose, and lignin) fiber. These are fermented into different short-chain fatty acids, such as butyrate and acetate, on the basis of the type of gut bacteria and the type of fiber. Butyrate acts on epithelial G protein–coupled receptors (GPCRs, e.g., GPR41, GPR43, and GPR109a) and as an epigenetic regulator by inhibiting histone deacetylase (HDAC) activity. Butyrate can increase serotonin synthesis, increase colonic contractility, alleviate visceral hypersensitivity, and augment the barrier. Physiological outcomes associated with irritable bowel syndrome (IBS) are shown in blue, and those associated with inflammatory bowel disease (IBD) are shown in green.