中国科学院上海药物研究所Wei Tang等研究人员合作发现，缺乏蛋氨酸-胆碱的饮食会通过肠道微生物紊乱和巨噬细胞浸润使DSS诱导的小鼠结肠炎恶化。这一研究成果于2024年4月29日在线发表在国际学术期刊《中国药理学报》上。

研究人员表示，溃疡性结肠炎（UC）与饮食习惯改变有关，主要与肠道微生物群失调、上皮细胞坏死和粘膜溃疡有关。在UC患者中发现了肝功能异常和肝脏代谢指数水平异常，这表明肠道疾病和肝脏疾病之间存在密切的相互作用。研究表明，蛋氨酸-胆碱缺乏饮食（MCD）可诱发肝炎期间肠道微生物群和代谢组的持续改变。

研究人员进一步探讨了UC患者的疾病表型，并研究了MCD是否是UC易感性的触发因素。在对88例UC患者的血清标本进行评估后，研究人员发现了明显的肝功能异常和血脂异常，包括 ALT、AST、TG、TC、LDL-c和HDL-c异常。DSS诱导的结肠炎小鼠的肝功能异常和血脂异常也得到了证实。研究人员用MCD喂养小鼠14天，造成轻度肝损伤，然后用DSS处理7天。

研究人员发现，在DSS诱导的急性、进行性和慢性结肠炎中，摄入MCD会明显加重粘膜炎症的发病机制，即促进粘膜溃疡、结肠缩短、腹泻、炎症免疫细胞浸润、细胞因子释放以及结肠和肝脏标本中炎症巨噬细胞的异常活化。腹腔注射氯膦酸盐脂质体在全身范围内清除巨噬细胞可显著降低MCD引发结肠炎的发病机理。

此外，摄入MCD明显改变了小鼠粪便、结肠和肝脏中短链脂肪酸（SCFA）的产生模式。研究人员证明，MCD诱导的结肠炎发病机制在很大程度上取决于肠道微生物，而且疾病表型可通过粪便微生物群移植（FMT）传播。总之，这项研究支持了，摄入MCD易导致实验性结肠炎并通过调节小鼠肠道微生物和巨噬细胞增强其发病机制的观点。

附：英文原文

Title: Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages

Author: Liu, Mo-ting, Zhang, Yao, Xiang, Cai-gui, Yang, Tao, Wang, Xiao-han, Lu, Qiu-kai, Lu, Hui-min, Fan, Chen, Feng, Chun-lan, Yang, Xiao-qian, Zou, Duo-wu, Li, Heng, Tang, Wei

Issue&Volume: 2024-04-29

Abstract: Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.

DOI: 10.1038/s41401-024-01291-y

Source: https://www.nature.com/articles/s41401-024-01291-y