Zhu Lanping, Luo Yang, Liu Yaxin, Sun Siyuan, Yuan Junjie, Zhang Lijun, Zhong Weilong, Ma Shuang, Yu Zihan, Zhou Jinjie, Chen Xin, Zhao Jingwen
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.
Front Microbiol. 2025 Mar 19;16:1509876. doi: 10.3389/fmicb.2025.1509876. eCollection 2025.
Nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a serious clinical complication with no effective treatments available. Modulating the intestinal microbiota through dietary and nutritional targets is a promising strategy for preventing NSAID enteropathy. This study aimed to investigate the protective effect and underlying mechanisms of the probiotic (CB) on indomethacin (IND)-induced enteropathy. C57BL/6J mice received CB treatment for 14 days along with concurrent IND gavage for the final 7 days. Caco2 cells were stimulated with IND to evaluate the effect of CB supernatant (CBS) on the intestinal barrier function, and LS174T cells were used to validate the modulatory action of CBS on the Notch signaling pathway. Our findings revealed that CB treatment prevented anorexia and weight loss, reduced the severity of enteropathy, and decreased the inflammatory response of the small intestine. CB also increased the expression of tight junction proteins and reduced permeability in mice and Caco2 cells. Additionally, CB suppressed apoptosis and promoted proliferation in the small intestine. Further research found that CB increased the number of goblet cells and MUC2 secretion. Mechanistically, CB may promote MUC2 secretion by suppressing the Notch signaling pathway, consistent with the results of intervention in LS174T cells with CBS. In conclusion, CB might prevent NSAID enteropathy by increasing MUC2 secretion through the inhibition of the Notch pathway. Our study identified the potential efficacy of CB as a preventive strategy against NSAID enteropathy and showed promising prospects for CB as a food supplement.
非甾体抗炎药（NSAID）肠病是一种严重的临床并发症，目前尚无有效的治疗方法。通过饮食和营养靶点调节肠道微生物群是预防NSAID肠病的一种有前景的策略。本研究旨在探讨益生菌（CB）对吲哚美辛（IND）诱导的肠病的保护作用及其潜在机制。C57BL/6J小鼠接受CB治疗14天，并在最后7天同时进行IND灌胃。用IND刺激Caco2细胞以评估CB上清液（CBS）对肠道屏障功能的影响，并使用LS174T细胞验证CBS对Notch信号通路的调节作用。我们的研究结果表明，CB治疗可预防厌食和体重减轻，降低肠病的严重程度，并减轻小肠的炎症反应。CB还增加了小鼠和Caco2细胞中紧密连接蛋白的表达并降低了通透性。此外，CB抑制了小肠中的细胞凋亡并促进了增殖。进一步的研究发现，CB增加了杯状细胞的数量和MUC2分泌。从机制上讲，CB可能通过抑制Notch信号通路来促进MUC2分泌，这与用CBS干预LS174T细胞的结果一致。总之，CB可能通过抑制Notch途径增加MUC2分泌来预防NSAID肠病。我们的研究确定了CB作为预防NSAID肠病的潜在功效，并显示了CB作为食品补充剂的广阔前景。
