Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice.
Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice.
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DOI：
10.1038/ncomms9141
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发表时间：
2015-08-25
影响因子：
16.6
通讯作者：
Hennet T
中科院分区：
文献类型：
--
作者：
Huang YL;Chassard C;Hausmann M;von Itzstein M;Hennet T
在肠道炎症过程中，微生物组成经常发生快速变化，但这种变化的机制仍然难以捉摸。在这里，我们证明了盲肠唾液酸酶活性的增加在赋予一些细菌生长优势方面是至关重要的，包括大肠杆菌（E。大肠杆菌）。这种唾液酸酶活性尤其源自普通拟杆菌，其肠道水平在葡聚糖硫酸钠给药后增加。唾液酸酶活性增加介导唾液酸从肠组织中释放，从而促进大肠杆菌的生长。大肠杆菌感染。E.大肠杆菌可能通过刺激肠树突状细胞产生促炎细胞因子而加剧炎症反应。口服唾液酸酶抑制剂和低水平的肠道α 2，3-连接唾液酸可降低E.大肠杆菌生长和小鼠结肠炎的严重程度。唾液酸催化剂的调节为治疗肠道炎症开辟了新的前景，如E。大肠杆菌生态失调。 肠道炎症通常与微生物群组成的变化有关，但机制尚不清楚。在这里，作者表明，在肠道炎症过程中发生的盲肠唾液酸酶活性的增加促进了肠杆菌科的扩张，这可能导致炎症反应加剧。
Rapid shifts in microbial composition frequently occur during intestinal inflammation, but the mechanisms underlying such changes remain elusive. Here we demonstrate that an increased caecal sialidase activity is critical in conferring a growth advantage for some bacteria including Escherichia coli (E. coli) during intestinal inflammation in mice. This sialidase activity originates among others from Bacteroides vulgatus, whose intestinal levels expand after dextran sulphate sodium administration. Increased sialidase activity mediates the release of sialic acid from intestinal tissue, which promotes the outgrowth of E. coli during inflammation. The outburst of E. coli likely exacerbates the inflammatory response by stimulating the production of pro-inflammatory cytokines by intestinal dendritic cells. Oral administration of a sialidase inhibitor and low levels of intestinal α2,3-linked sialic acid decrease E. coli outgrowth and the severity of colitis in mice. Regulation of sialic acid catabolism opens new perspectives for the treatment of intestinal inflammation as manifested by E. coli dysbiosis. Intestinal inflammation is often associated with a shift in microbiota composition but the mechanisms are unclear. Here the authors show that an increase in caecal sialidase activity occurring during intestinal inflammation promotes the expansion of Enterobacteriaceae, which can lead to exacerbated inflammatory response.