Department of Surgery, Nanjing Drum Tower Hospital, Nanjing 210008, China.
Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, China.
Food Funct. 2021 Mar 15;12(5):2201-2210. doi: 10.1039/d0fo02786c.
Gut microbiota takes part in the pathogenesis of inflammatory bowel disease (IBD). Clinical research has found that probiotics have a beneficial effect on active ulcerative colitis, but to date, significant efficacy has rarely been found in the use of probiotics in the remission phase of ulcerative colitis and Crohn's disease. More studies are needed to assess the utilization of probiotics in IBD remission. In this study, we assessed the administration of Bacillus subtilis in remission and its possible mechanism in mice with IBD. Oral administration of B. subtilis was implemented for 6 weeks (dextran sulfate sodium (DSS)-P6w group), 2 weeks (DSS-P2w group) or 0 weeks (DSS-control(CT) group) in the remission phase in rodents with (DSS)-induced IBD. The body weight, colon length and disease activity index (DAI) were recorded, and colon H&E staining was performed. The expression of tight junction proteins (ZO-1 and occludin) mRNA and epithelium proliferation-related Ki67 was detected. Gut microbiota were tested by 16S rRNA sequencing. Administration of B. subtilis in remission effectively increased the body weight and colon length and decreased DAI in the DSS-P6w group compared with the DSS-CT group, but there is no significant difference between the DSS-P2w and DSS-CT groups. The epithelial integrity was improved, and the expression of ZO-1 and occludin increased due to administration of B. subtilis in remission, which was more evident in the DSS-P6w group. The expression of Ki67 increased in the DSS-CT group compared with that in the CT group. The administration of B. subtilis effectively down-regulated the expression of Ki67 in the DSS-P6w and DSS-P2w groups compared with the DSS-CT group. Furthermore, gut microbial structure was improved, with significantly decreased Escherichia/Shigella and Enterococcus, and increased Akkermansia and corresponding microbial function in the DSS-P6w group. Short-term administration of B. subtilis in the remission phase showed no significant improvement in mice with IBD. Long-term and continuous supplementation of B. subtilis in remission could effectively maintain the remission by protecting epithelial integrity, regulating proliferation of intestinal epithelial cells, and improving gut microbiota and the corresponding microbial function.
肠道微生物群参与炎症性肠病（IBD）的发病机制。临床研究发现益生菌对活动性溃疡性结肠炎有益，但迄今为止，在溃疡性结肠炎和克罗恩病的缓解期使用益生菌很少发现显著疗效。需要更多的研究来评估益生菌在 IBD 缓解期的应用。在这项研究中，我们评估了枯草芽孢杆菌在 IBD 缓解期的给药及其在 IBD 模型小鼠中的可能机制。在（葡聚糖硫酸钠（DSS））诱导的 IBD 缓解期，给小鼠口服枯草芽孢杆菌 6 周（DSS-P6w 组）、2 周（DSS-P2w 组）或 0 周（DSS-对照（CT）组）。记录体重、结肠长度和疾病活动指数（DAI），并进行结肠 H&E 染色。检测紧密连接蛋白（ZO-1 和 occludin）mRNA 和上皮细胞增殖相关 Ki67 的表达。通过 16S rRNA 测序检测肠道微生物群。与 DSS-CT 组相比，缓解期给予枯草芽孢杆菌可有效增加 DSS-P6w 组的体重和结肠长度，降低 DAI，但 DSS-P2w 组与 DSS-CT 组之间无显著差异。枯草芽孢杆菌缓解期给药可改善上皮完整性，增加 ZO-1 和 occludin 的表达，DSS-P6w 组更为明显。与 CT 组相比，DSS-CT 组 Ki67 的表达增加。枯草芽孢杆菌可有效下调 DSS-P6w 和 DSS-P2w 组 Ki67 的表达，与 DSS-CT 组相比。此外，枯草芽孢杆菌缓解期给药可改善肠道微生物结构，显著降低大肠杆菌/志贺氏菌和肠球菌，增加阿克曼氏菌，相应微生物功能也增加，DSS-P6w 组最为明显。缓解期短时间给予枯草芽孢杆菌对 IBD 模型小鼠无明显改善。缓解期长期连续补充枯草芽孢杆菌可有效维持缓解，保护上皮完整性，调节肠上皮细胞增殖，改善肠道微生物群及其相应的微生物功能。
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