Akkermansia muciniphila and its outer membrane protein Amuc_1100 prophylactically attenuate 5-fluorouracil-induced
Shoujun Chen1, Kaiyue Qian1, Guanghui Zhang1
1School of Life Sciences, Anhui University, Hefei, 230601, Anhui, China; Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, 230601, Anhui, China.
Abstract:
5-Fluorouracil (5-FU) is a chemotherapy drug used to treat tumors. Previous studies have shown that Akkermansia muciniphila (A. muciniphila) and its outer membrane protein, Amuc_1100, alleviate dextran sodium sulfate (DSS)-induced colitis in mice. We investigated the effects of both A. muciniphila and Amuc_1100 on 5-FU-induced intestinal mucosal damage in mice. C57BL/6 mice were gavaged with A. muciniphila or Amuc_1100 daily before, during, and after 5-FU injection for a total of 14 days. By evaluating diarrheal toxicity scores, body weight changes, colonic anatomy images, and histopathology of intestinal injury in these mice, we found that A. muciniphila and Amuc_1100 alleviated 5-FU-induced intestinal mucositis. Quantitative polymerase chain reaction assays of intestinal cytokine mRNA levels demonstrated that both A. muciniphila and Amuc_1100 attenuated the upregulation of intestinal Tumor Necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) induced by 5-FU treatment. In addition, they both reduced 5-FU-induced the NLR family pyrin domain containing 3 (NLRP3) inflammatory vesicle activation. Furthermore, by monitoring the mRNA expression of tight junction proteins in the intestine, we found that A. muciniphila and Amuc_1100 were capable of restoring the damaged intestinal barrier. Notably, A. muciniphila and Amuc_1100 also played a role in altering the structure of the intestinal microbial community. The present study revealed the protective role of both A. muciniphila and Amuc_1100 in the intestinal mucositis caused by 5-FU, providing new insights into treatment options.
Insights
Akkermansia muciniphila and its protein Amuc_1100 protect against chemotherapy-induced intestinal damage. These interventions reduce inflammation, restore gut barrier function, and alter the gut microbiome, offering new therapeutic possibilities.
Area of Science:
- Microbiology
- Gastroenterology
- Pharmacology
Background:
- 5-Fluorouracil (5-FU) is a widely used chemotherapy agent.
- 5-FU can cause significant gastrointestinal side effects, including mucositis.
- Akkermansia muciniphila (A. muciniphila) and its outer membrane protein Amuc_1100 have shown protective effects against colitis.
Purpose of the Study:
- To investigate the protective effects of A. muciniphila and Amuc_1100 against 5-FU-induced intestinal mucositis in mice.
- To elucidate the underlying mechanisms of this protection, including inflammatory responses and gut barrier integrity.
Main Methods:
- Mice were treated with A. muciniphila or Amuc_1100 daily before, during, and after 5-FU injection.
- Evaluated outcomes included diarrheal toxicity, body weight changes, colonic anatomy, and intestinal histopathology.
- Quantitative PCR was used to assess cytokine mRNA levels (TNF-α, IL-6), NLRP3 inflammasome activation, and tight junction protein expression.
Main Results:
- A. muciniphila and Amuc_1100 significantly alleviated 5-FU-induced intestinal mucositis.
- Both interventions attenuated the upregulation of TNF-α and IL-6, and reduced NLRP3 inflammasome activation.
- Treatment restored the expression of intestinal tight junction proteins, indicating repair of the gut barrier.
- A. muciniphila and Amuc_1100 also modulated the structure of the intestinal microbial community.
Conclusions:
- A. muciniphila and Amuc_1100 demonstrate a protective role against 5-FU-induced intestinal mucositis.
- These findings suggest potential therapeutic applications of A. muciniphila and Amuc_1100 for managing chemotherapy-related gastrointestinal toxicity.
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