Ikeda Eri, Yamaguchi Masaya, Kawabata Shigetada
Department of Microbiology, Graduates School of Dentistry, Osaka University, Suita, Osaka, Japan.
Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Gastro Hep Adv. 2024 Feb 6;3(4):461-470. doi: 10.1016/j.gastha.2024.01.016. eCollection 2024.
Gut dysbiosis characterized by an imbalanced microbiota is closely involved in the pathogenesis of a widespread gastrointestinal inflammatory disorder, inflammatory bowel disease. However, it is unclear how the complex intestinal microbiota affects development or resistant of mucosal inflammation. Our aim was to investigate the impact of the gut microbiota on susceptibility in a mouse model of ulcerative colitis.
We compared the susceptibility to dextran sulfate sodium (DSS)-induced colitis of inbred BALB/c mice obtained from the 3 main distributors of laboratory animals in Japan. Clinical symptoms of the colitis and the faecal microbiota were assessed. Cohousing approach was used to identify whether the gut microbiota is a primary factor determining disease susceptibility.
Here, we showed differences in the susceptibility of BALB/c mice from the vendors to DSS colitis. Analysis of the gut microbiota using 16S ribosomal RNA sequencing revealed clear separation of the gut microbial composition among mice from the vendors. Notably, the abundance of the phylum was strongly associated with disease activity. We also observed the expansion of butyrate-producing species in mice with decreased susceptibility of the disease. Further cohousing experiments showed that variation in clinical outcomes was more correlated with the gut microbiota than genetic variants among substrains from different suppliers.
A BALB/c substrain that was resistant to DSS-induced colitis was observed, and the severity of DSS-induced colitis was mainly influenced by the gut microbiota. Targeting butyrate-producing bacteria could have therapeutic potential for ulcerative colitis.
以微生物群失衡为特征的肠道生态失调与一种广泛的胃肠道炎症性疾病——炎症性肠病的发病机制密切相关。然而，尚不清楚复杂的肠道微生物群如何影响黏膜炎症的发展或抗性。我们的目的是在溃疡性结肠炎小鼠模型中研究肠道微生物群对易感性的影响。
我们比较了从日本3家主要实验动物供应商处获得的近交系BALB/c小鼠对葡聚糖硫酸钠（DSS）诱导的结肠炎的易感性。评估了结肠炎的临床症状和粪便微生物群。采用同笼饲养方法来确定肠道微生物群是否是决定疾病易感性的主要因素。
在此，我们展示了来自不同供应商的BALB/c小鼠对DSS结肠炎易感性的差异。使用16S核糖体RNA测序对肠道微生物群进行分析，结果显示来自不同供应商的小鼠肠道微生物组成有明显区分。值得注意的是，某一门的丰度与疾病活动密切相关。我们还观察到在疾病易感性降低的小鼠中，产丁酸菌物种有所增加。进一步的同笼饲养实验表明，临床结果的差异与肠道微生物群的相关性比与来自不同供应商的亚系之间的基因变异的相关性更大。
观察到一种对DSS诱导的结肠炎具有抗性的BALB/c亚系，DSS诱导的结肠炎的严重程度主要受肠道微生物群的影响。针对产丁酸菌可能对溃疡性结肠炎具有治疗潜力。
