医学
肠道菌群
肠道通透性
炎症性肠病
势垒函数
内科学
免疫系统
细菌易位
微生物群
脂多糖
促炎细胞因子
作者
Kirstin Andersen,Marie Sophie Kesper,Julian A. Marschner,Lukas Konrad,Mi Heon Ryu,Santhosh V. Kumar,Onkar P. Kulkarni,Shrikant R. Mulay,Simone Romoli,Jana Demleitner,Patrick Schiller,Alexander Dietrich,Susanna Müller,Oliver Groß,Hans‐Joachim Ruscheweyh,Daniel H. Huson,Bärbel Stecher,Hans‐Joachim Anders
出处
期刊:Journal of The American Society of Nephrology
日期:2016-05-05
卷期号:28 (1): 76-83
被引量:175
标识
DOI:10.1681/asn.2015111285
摘要
CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α 3–deficient mice with Alport syndrome–related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen–presenting cells, CD4 and CD8 T cells, and Th17– or IFNγ–producing T cells in the spleen as well as regulatory T cell suppression. CKD–related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD–related systemic inflammation and its consequences.
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