肠道纤维化中菌群或起关键作用

肿瘤坏死因子样细胞因子1A(TL1A)在IBD中起作用,可调节肠道炎症及纤维化的位置及严重程度;
在炎症性肠道黏膜中,TL1A表达增加,且与纤维化狭窄型克罗恩病相关;
过表达Tl1a引起小鼠的自发性回肠炎,恶化近端结肠炎及纤维化,在缺失肠道菌群的小鼠中过表达Tl1a则无上述炎症表型;
将SPF小鼠或健康人的粪便菌群移植给Tl1a转基因无菌小鼠及野生型无菌小鼠,移植了SPF小鼠菌群的Tl1a转基因小鼠,肠道胶原沉积及成纤维细胞活化增加。
延伸阅读
Mucosal Immunology [IF:7.36]

Inflammation-independent TL1A-mediated intestinal fibrosis is dependent on the gut microbiome

炎症依赖性TL1A介导的肠道纤维化依赖于肠道菌群

2018-07-09, Article, 10.1038/s41385-018-0055-ymore

Abstract:
Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease (IBD), modulating the location and severity of intestinal inflammation and fibrosis. TL1A expression is increased in inflamed gut mucosa and associated with fibrostenosing Crohn’s disease. Tl1a-overexpression in mice lead to spontaneous ileitis, and exacerbated induced proximal colitis and fibrosis. IBD is associated with shifts in the gut microbiome, but the effect of differing microbial populations and their interaction with TL1A on fibrosis has not been investigated. We demonstrate that the pro-fibrotic and inflammatory phenotype resulting from Tl1a-overexpression is abrogated in the absence of resident microbiota. To evaluate if this is due to the absence of a unique bacterial population, as opposed to any bacteria per se, we gavaged germ-free (GF) wild-type and Tl1a-transgenic (Tl1a-Tg) mice with stool from specific pathogen free (SPF) mice and a healthy human donor (Hu). Reconstitution with SPF, but not Hu microbiota, resulted in increased intestinal collagen deposition and fibroblast activation in Tl1a-Tg mice. Notably, there was reduced fibroblast migration and activation under GF conditions compared to native conditions. We then identified several candidate organisms that correlated directly with increased fibrosis in reconstituted mice and showed that these organisms directly impact fibroblast function in vitro. Thus, Tl1a-mediated intestinal fibrosis and fibroblast activation are dependent on specific microbial populations.

First Authors:
Noam Jacob

Correspondence Authors:
Noam Jacob,David Q Shih

All Authors:
Noam Jacob,Jonathan Jacobs,Kotaro Kumagai,Connie W Y Ha,Yoshitake Kanazawa,Venu Lagishetty,Katherine Altmayer,Ariel M Hamill,Aimee Von Arx,R Balfour Sartor,Suzanne Devkota,Jonathan Braun,Kathrin S Michelsen,Stephan R Targan,David Q Shih