ena-STUDY-Xinqiao Hospital,The Army Medical University, Chongqing,China-07-04-2021-11:24:40:455-848
Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). Toll-like-receptor 4(TLR4) serves as the hub mediating the crosstalk between the intestinal commensal microbiome and host immunity. However, the impact of TLR4 on the shaping of intestinal microbiota and host immunity remains poorly characterized.
Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation. Toll-like-receptor 4 (TLR4) serves as the hub mediating the crosstalk between the intestinal microbiome and host immunity. We report here that TLR4 deficiency-mediated dysbiosis gives rise to enhanced predisposition of transmissible colon inflammation in mice. Decreased abundance of Akkermansia muciniphila (A. muciniphila) and the reduced proportion of suppressive ROR?t+ Treg cells in lamina propria (LP) contribute to the pronounced susceptibility to colitis in TLR4-/- mice. Reciprocal microbiota transplantation demonstrate disease risk was decreased in TLR4-/- host that were recolonized with gut microbiota from wild-type (WT) mice accompanied with increased abundance of A. muciniphila and ROR?t+ Treg cells. Mucosal biopsies from healthy participants manifested paralleled correlation between TLR4 expression and A. muciniphila colonization. Targeting specific PRRs and therefore regulating colonic microbial ecology, as detected in TLR4, might provide potential therapeutic approach in the treatment of human intestinal disorders.
Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation. Toll-like-receptor 4 (TLR4) serves as the hub mediating the crosstalk between the intestinal microbiome and host immunity. We report here that TLR4 deficiency-mediated dysbiosis gives rise to enhanced predisposition of transmissible colon inflammation in mice. Decreased abundance of Akkermansia muciniphila (A. muciniphila) and the reduced proportion of suppressive ROR?t+ Treg cells in lamina propria (LP) contribute to the pronounced susceptibility to colitis in TLR4-/- mice. Reciprocal microbiota transplantation demonstrate disease risk was decreased in TLR4-/- host that were recolonized with gut microbiota from wild-type (WT) mice accompanied with increased abundance of A. muciniphila and ROR?t+ Treg cells. Mucosal biopsies from healthy participants manifested paralleled correlation between TLR4 expression and A. muciniphila colonization. Targeting specific PRRs and therefore regulating colonic microbial ecology, as detected in TLR4, might provide potential therapeutic approach in the treatment of human intestinal disorders.