Piperine Improves DSS‐Induced Colitis in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota

Jun 2, 2025Phytotherapy research : PTR

Piperine reduces inflammation and changes gut bacteria to improve colitis in mice

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Abstract

Piperine administration increased colon length and reduced spleen index in a mouse model of colitis.

Piperine may ameliorate colitis symptoms and inflammation in mice exposed to dextran sulfate sodium (DSS).
The treatment enhanced intestinal barrier integrity by increasing specific proteins associated with gut health.
Piperine modulated inflammatory responses by inhibiting a signaling pathway, leading to decreased pro-inflammatory molecules.
16S rDNA sequencing indicated an increase in the abundance of the gut bacterium Dubosiella with piperine treatment.
The findings suggest that gut microbiota plays a significant role in the protective effects of piperine against intestinal damage.

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Inflammatory bowel disease (IBD) is a global health concern with limited therapeutic options. Previous studies have demonstrated that piperine exhibited anti-inflammatory effects both in vitro and in vivo. However, its potential to ameliorate colitis in mice through modulation of gut microbiota has not been explored. This study aimed to investigate the role of gut microbiota in the protective effects of piperine against colitis using a dextran sulfate sodium (DSS)-induced mouse model. Mice were administered piperine (12.5 and 25 mg/kg) prior to DSS exposure. Fecal microbiota transplantation (FMT) was then performed, after which we evaluated colitis symptoms, inflammation levels, and intestinal barrier function. Subsequently, 16S rDNA-based high-throughput sequencing was employed to analyze the microbial composition of the mouse cecal contents. Piperine administration increased the colon length, decreased the spleen index, and improved colon histopathology. Furthermore, piperine modulated inflammatory responses by inhibiting NF-κB signaling, thereby reducing the release of pro-inflammatory cytokines and mediators. It also enhanced intestinal barrier integrity by increasing the expression of claudin-1, claudin-3, ZO-1, occludin, and mucin 2. Notably, the 16S rDNA sequencing results revealed that piperine increased the abundance of Dubosiella in the gut. Piperine effectively protected mice from DSS-induced colitis, suppressed inflammation, and improved poor intestinal barrier function. It reshaped the intestinal microbiota, ultimately alleviating DSS-induced colitis in mice. Our research highlighted the significant role of gut microbiota in the piperine-mediated alleviation of intestinal damage and suggested its therapeutic potential for promoting gut health and reducing the risk of colitis.

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Piperine Improves DSS‐Induced Colitis in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota

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