Spicy food intake and dietary factors shape the gut microbiome and metabolism of mucin and short-chain fatty acids in healthy adults.

Whether spicy food intake independently modulates mucin metabolism and short-chain fatty acid (SCFA) production or depends on co-ingested factors such as alcohol remains poorly understood. Herein, shotgun metagenomics characterized gut microbial composition, functional pathways, and their relationship with spicy food intake, alcohol consumption, and intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) levels in 229 healthy Korean adults. Alcohol intake was positively correlated with urinary I-FABP levels indicating mild epithelial stress, whereas spicy food intake was not associated with either FABP biomarker. Consumption of highly spicy foods resulted in increased abundance of SCFA-producing and mucin-metabolizing taxa, along with mucin degradation and SCFA production. Individuals with high alcohol intake showed stronger enrichment of mucin-degrading taxa with reduced SCFA flux and increased abundance of Proteobacteria and Fusobacteria. The cross-classified dietary groups exhibited distinct mucin and SCFA activity patterns. The Drink-High-Spicy-High (DHSH) group displayed elevated mucin turnover and SCFA production with dysbiosis. These findings suggest that spicy food may modulate mucus layer metabolism in a context-dependent manner, whereas alcohol more consistently perturbs mucin-SCFA networks and epithelial integrity.