# Spermine Ameliorates DSS-Induced Ulcerative Colitis in Mice by Improving Mitophagy and Intestinal Microbiota

## TL;DR

Spermine helps treat ulcerative colitis in mice by reducing inflammation, improving cell function, and balancing gut bacteria.

## Contribution

This study reveals spermine's novel therapeutic effects on colitis via mitophagy and microbiota modulation.

## Key findings

- Spermine upregulates tight junction protein occludin and inhibits NLRP3-mediated inflammation in DSS-treated mice.
- Spermine enhances mitophagy by increasing PINK1, Parkin, and LC3-II levels in colitis mice.
- Spermine improves gut microbiota composition by increasing Muribaculaceae and decreasing Firmicutes and Blautia.

## Abstract

Spermine (Spe) plays a critical role in maintaining the integrity of the intestinal barrier and promoting intestinal development. However, the therapeutic role of Spe on ulcerative colitis (UC) remains unclear. This study aims to research the impact and mechanism of Spe on dextran sulfate sodium (DSS)-induced colitis in mice. Twenty-eight C57BL/6 mice were orally administered Spe before and during DSS treatment to evaluate its protective effects. Lipopolysaccharides (LPSs) were used to construct an in vitro UC model in IEC-6 cells. The study indicates that Spe treatment upregulated the expression of tight junction protein occludin and inhibited NLRP3 mediated inflammatory response by downregulating the levels of NLRP3, Caspase-1, IL-1β, IL-18 and TNF-α in the colon of DSS-treated mice. In addition, Spe enhanced mitophagy in colitis mice by increasing expressions of mitophagy factors (PINK1, Parkin, LC3-II) in DSS-treated mice. PINK1-mediated mitophagy helps alleviate LPS-induced mitochondrial damage in IEC-6 cells. Furthermore, Spe regulates the gut microbiota composition in mice with colitis by increasing the abundance of unclassified Muribaculaceae, reducing the levels of Firmicutes and Blautia, and lowering the Firmicutes/Bacteroidetes ratio. In conclusion, spermine exhibited treatment efficacy on DSS-induced colitis by inhibiting NLRP3-mediated inflammatory response, promoting mitophagy and improving intestinal microbial dysbiosis.