Transepithelial Barrier Dysfunction Drives Microbiota Dysbiosis to Initiate Epithelial Clock-driven Inflammation.

ABSTRACT:

Background

Factors that contribute to inflammatory bowel disease [IBD] pathogenesis include genetic polymorphisms, barrier loss, and microbial dysbiosis. A major knowledge gap exists in the origins of the colitogenic microbiome and its relationship with barrier impairment. Epithelial myosin light chain kinase [MLCK] is a critical regulator of the paracellular barrier, but the effects of MLCK activation on the intraepithelial bacteria [IEB] and dysbiosis are incompletely understood. We hypothesise that MLCK-dependent bacterial endocytosis promotes pathobiont conversion and shapes a colitogenic microbiome.

Methods

To explore this, transgenic [Tg] mice with barrier loss induced by intestinal epithelium-specific expression of a constitutively active MLCK were compared with wild-

SUBMITTER: Pai YC 

PROVIDER: S-EPMC10588795 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature