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Capsaicin (CAP) is an ingredient of peppers that has biological activities at low doses but causes gastrointestinal (GI) discomfort at high doses. However, the GI effects of high doses of CAP and the evaluation criteria to determine this remain unknown. To elucidate the dose-related effects of CAP on GI health, CAP was administered to mice at 40, 60, and 80 mg/kg doses. The results showed that 40 mg/kg CAP did not negatively affect GI tissues, while 60 and 80 mg/kg CAP damaged GI tissues and caused significant inflammation in the jejunum, ileum, and colon. The levels of serum substance P (SP) and calcitonin gene-related peptide (CGRP) were CAP-dose-dependent, and short-chain fatty acids (SCFAs) content significantly increased in the 80 mg/kg group. Correlation analysis revealed that the underlying mechanisms might be related to the regulation of gut microbiota, especially Bifidobacterium, Lactobacillus, Faecalibacterium, and Butyricimonas. These results suggest that oral administration of 60 and 80 mg/kg CAP in mice causes intestinal inflammation and high levels of serum neuropeptides and cecal SCFAs, which may be related to alterations in gut microbiota.

Capsaicin, the Spicy Ingredient of Chili Peppers: Effects on Gastrointestinal Tract and Composition of Gut Microbiota at Various Dosages