School 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.
School 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.
Biochem Biophys Res Commun. 2022 Jul 23;614:34-40. doi: 10.1016/j.bbrc.2022.04.135. Epub 2022 May 3.
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.
5-氟尿嘧啶（5-FU）是一种用于治疗肿瘤的化疗药物。先前的研究表明，阿克曼氏菌（Akkermansia muciniphila，A. muciniphila）及其外膜蛋白 Amuc_1100 可缓解葡聚糖硫酸钠（Dextran sodium sulfate，DSS）诱导的小鼠结肠炎。我们研究了 A. muciniphila 和 Amuc_1100 对 5-FU 诱导的小鼠肠道黏膜损伤的影响。C57BL/6 小鼠在 5-FU 注射前、期间和后每日灌胃 A. muciniphila 或 Amuc_1100，共 14 天。通过评估这些小鼠的腹泻毒性评分、体重变化、结肠解剖图像和肠道损伤的组织病理学，我们发现 A. muciniphila 和 Amuc_1100 缓解了 5-FU 诱导的肠道黏膜炎。肠道细胞因子 mRNA 水平的定量聚合酶链反应检测表明，A. muciniphila 和 Amuc_1100 均可减弱 5-FU 治疗引起的肠道肿瘤坏死因子-α（Tumor Necrosis Factor-α，TNF-α）和白细胞介素-6（Interleukin-6，IL-6）的上调。此外，它们均减少了 5-FU 诱导的 NLR 家族包含 pyrin 域的 3（NLRP3）炎性小体激活。此外，通过监测肠道中紧密连接蛋白的 mRNA 表达，我们发现 A. muciniphila 和 Amuc_1100 能够恢复受损的肠道屏障。值得注意的是，A. muciniphila 和 Amuc_1100 还可以改变肠道微生物群落的结构。本研究揭示了 A. muciniphila 和 Amuc_1100 在 5-FU 引起的肠道黏膜炎中的保护作用，为治疗选择提供了新的见解。
