Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
复制标题
DOI：
10.3389/fmicb.2019.02259
复制
发表时间：
2019-10-01
影响因子：
5.2
通讯作者：
Li, Lanjuan
中科院分区：
文献类型：
--
作者：
Bian, Xiaoyuan;Wu, Wenrui;Li, Lanjuan
炎症性肠病（IBD）的发展是基因、先天免疫和环境因素之间复杂相互作用的结果，这些因素与肠道微生物群有关。多项临床和动物数据表明，嗜粘蛋白阿克曼氏菌与健康粘膜相关。然而，其在结肠炎中的确切作用目前尚不清楚。我们的研究旨在确定其在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中的保护作用和潜在机制。24只C57BL/6雄性小鼠给予A.嗜粘蛋白Muc（T）或磷酸盐缓冲盐水（PBS）通过口服管饲法每天一次持续14天。通过在第0天至第6天饮用2%DSS，然后饮用正常水2天，诱发结肠炎。每天称重小鼠，然后在第8天处死。我们发现A.嗜粘蛋白体改善了DSS诱导的结肠炎，这通过减少的体重减轻、结肠长度缩短和组织病理学评分以及增强的屏障功能来证明。血清和组织中炎性细胞因子和趋化因子（TNF-α、IL 1 α、IL 6、IL 12 A、MIP-1A、G-CSF和KC）的水平由于A.嗜粘蛋白体施用。16S rDNA序列分析表明，A.嗜粘蛋白菌诱导显著的肠道微生物群改变。相关性分析表明，促炎细胞因子和其他损伤因子与疣微菌属、阿克曼菌属、瘤胃球菌科和Rikenellaceae呈负相关，且在A.嗜粘蛋白处理的小鼠。我们证实A.嗜粘蛋白治疗可以通过微生物与宿主的相互作用（保护肠道屏障功能并降低炎症细胞因子水平）或通过改善微生物群落来改善粘膜炎症。我们的研究结果表明，A.嗜粘蛋白菌可能是一种潜在的改善结肠炎的益生菌制剂。
Inflammatory bowel diseases (IBDs) develop as a result of complex interactions among genes, innate immunity and environmental factors, which are related to the gut microbiota. Multiple clinical and animal data have shown that Akkermansia muciniphila is associated with a healthy mucosa. However, its precise role in colitis is currently unknown. Our study aimed to determine its protective effects and underlying mechanisms in a dextran sulfate sodium (DSS)-induced colitis mouse model. Twenty-four C57BL/6 male mice were administered A. muciniphila Muc(T) or phosphate-buffered saline (PBS) once daily by oral gavage for 14 days. Colitis was induced by drinking 2% DSS from days 0 to 6, followed by 2 days of drinking normal water. Mice were weighed daily and then sacrificed on day 8. We found that A. muciniphila improved DSS-induced colitis, which was evidenced by reduced weight loss, colon length shortening and histopathology scores and enhanced barrier function. Serum and tissue levels of inflammatory cytokines and chemokines (TNF-alpha, IL1 alpha, IL6, IL12A, MIP-1A, G-CSF, and KC) decreased as a result of A. muciniphila administration. Analysis of 16S rDNA sequences showed that A. muciniphila induced significant gut microbiota alterations. Furthermore, correlation analysis indicated that pro-inflammatory cytokines and other injury factors were negatively associated with Verrucomicrobia, Akkermansia, Ruminococcaceae, and Rikenellaceae, which were prominently abundant in A. muciniphila-treated mice. We confirmed that A. muciniphila treatment could ameliorate mucosal inflammation either via microbe-host interactions, which protect the gut barrier function and reduce the levels of inflammatory cytokines, or by improving the microbial community. Our findings suggest that A. muciniphila may be a potential probiotic agent for ameliorating colitis.