Mohammadi Mohammad, Rahimi Kaveh, Rezaie Anahita, Tabandeh Mohammad Reza
Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Sci Rep. 2025 Apr 28;15(1):14831. doi: 10.1038/s41598-025-96948-x.
The purpose of this study was to investigate the function of the NLRP3-Caspase 1 signaling pathway in the colon during fecal microbiota transplantation (FMT) in colitis induced by acetic acid. Additionally, the study aimed to determine the impact of FMT on anxiety behaviors by analyzing the function of the NLRP3-Caspase 1 signaling pathway in the hippocampus. A total of twenty-four rats were selected randomly for the study and divided into two groups, a control group, and an acid acetic-induced colitis group. The acid acetic-induced colitis group further consisted of three subgroups: untreated acid acetic-induced colitis group, mesalazine 0.3 gr/kg group, and FMT group. After 6 days, the colon was evaluated for macroscopic and microscopic damage, and the signaling pathway NLRP3-Caspase1-related genes in the colon and hippocampus were analyzed. Additionally, anxiety-related behaviors of the rats were observed. FMT decreased colonic mRNA expression levels of NLRP3, NF-кB, and Caspase1 and pro-inflammatory cytokines (IL-1β and IL-18). Also, FMT reduced the expression of NLRP3, NF-κB, and Caspase1 protein levels as well as pro-inflammatory cytokines IL-1β and IL-18 in the hippocampus, resulting in a reduction of anxiety behaviors in the open field and elevated plus maze tests in the colitis model. FMT may improve acetic acid-induced colitis by regulating the NLRP3-Caspase1 signaling pathway in the colon. It also reduced colitis-induced anxiety behavior by regulating the expression of proteins related to the NLRP3-Caspase 1 pathway in the hippocampus.
本研究的目的是探讨在乙酸诱导的结肠炎粪便微生物群移植(FMT)过程中,NLRP3-半胱天冬酶1信号通路在结肠中的作用。此外,该研究旨在通过分析海马体中NLRP3-半胱天冬酶1信号通路的功能,确定FMT对焦虑行为的影响。总共随机选择24只大鼠进行研究,并分为两组,即对照组和乙酸诱导的结肠炎组。乙酸诱导的结肠炎组进一步分为三个亚组:未治疗的乙酸诱导的结肠炎组、美沙拉嗪0.3克/千克组和FMT组。6天后,评估结肠的宏观和微观损伤,并分析结肠和海马体中NLRP3-半胱天冬酶1相关信号通路基因。此外,观察大鼠的焦虑相关行为。FMT降低了结肠中NLRP3、NF-κB和半胱天冬酶1以及促炎细胞因子(IL-1β和IL-18)的mRNA表达水平。此外,FMT降低了海马体中NLRP3、NF-κB和半胱天冬酶1蛋白水平以及促炎细胞因子IL-1β和IL-18的表达,从而减少了结肠炎模型在旷场试验和高架十字迷宫试验中的焦虑行为。FMT可能通过调节结肠中的NLRP3-半胱天冬酶1信号通路来改善乙酸诱导的结肠炎。它还通过调节海马体中与NLRP3-半胱天冬酶1通路相关的蛋白质表达,减少了结肠炎诱导的焦虑行为。