Desulfovibrio-Hydrogen Sulfide Mediates Capsaicin-Induced Oxidative Stress and Gut Inflammation via TXNIP/NLRP3 Pathway

Abstract

The intake of capsaicin can disrupt the gut microecology and impact health, yet its underlying mechanism is not fully elucidated. This study, by establishing capsaicin-induced human microbiota-associated (HMA) mouse models revealed the molecular mechanism by which capsaicin perturbs the gut microbiota and metabolites, leading to intestinal barrier dysfunction, inflammation, and oxidative stress. This study demonstrated that capsaicin intake significantly increased the abundance of Desulfovibrio and raised the level of hydrogen sulfide (H₂S). Concurrently, the abundance of Faecalibacterium prausnitzii, which shared a symbiotic relationship with Desulfovibrio, also increased. These changes resulted in impaired intestinal barrier function, oxidative stress, and inflammation. Through microbe-colonization and chromate (an H₂S inhibitor) intervention experiments, it was confirmed that H₂S, the metabolite of Desulfovibrio, mediated oxidative stress and triggered capsaicin-induced gut inflammation by activating the Thioredoxin-interacting protein (TXNIP)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) pathway. This study elucidated the mechanism by which capsaicin impaired gut health via the Desulfovibrio-H₂S-TXNIP/NLRP3 pathway. It also provided a new target for improving and preventing intestinal health problems caused by dietary capsaicin.

Keywords

capsaicin / Desulfovibrio / Faecalibacterium prausnitzii / gut inflammation / hydrogen sulfide

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2026 The Author(s). Food Bioengineering published by John Wiley & Sons Australia, Ltd. on behalf of State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology.