N-glycosylation enzyme Mpi is essential for mucin O-glycosylation, host-microbe homeostasis, Paneth cell defense, and metabolism.

ABSTRACT: Intestinal homeostasis relies on a protective mucus layer that separates bacteria from the host, with Muc2 as its primary component. This secreted, gel-forming mucin is heavily O-glycosylated, allowing it to retain water and support beneficial bacteria. For the first time, we demonstrate that Muc2 N-glycosylation plays a critical in mucin maturation, O-glycosylation, barrier integrity, and the prevention of dysbiosis. Using mouse models with global and intestine-specific N-glycan deficiency- caused by the loss of the mannose producing enzyme, Mpi- we uncover an unexpected link between N-glycosylation and intestinal homeostasis. Our findings reveal that Mpi hypomorphic mice are highly sensitive to DSS-induced colitis, while Mpiflox; VillinCre mice spontaneously develop disease, exhibiting i

SUBMITTER: SoRelle J 

PROVIDER: S-EPMC11975007 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature