Postnatal 14D is the Key Window for Mice Intestinal Development- An Insight from Age-Dependent Antibiotic-Mediated Gut Microbial Dysbiosis Study.

Abstract

The postnatal period is one of the critical windows for the structure-function development of the gastrointestinal tract and associated mucosal immunity. Along with other constituent members, recent studies suggest the contribution of gut microbiota in maintaining host health, immunity, and development. Although the gut microbiota's role in maintaining barrier integrity is known, its function in early life development still needs to be better understood. To understand the details of gut microbiota's effects on intestinal integrity, epithelium development, and immune profile, the route of antibiotic-mediated perturbation is taken. Mice on days 7(P7D), 14(P14D), 21(P21D) and 28(P28D) are sacrificed and 16S rRNA metagenomic analysis is performed. The barrier integrity, tight junction proteins (TJPs) expression, intestinal epithelial cell (IEC) markers, and inflammatory cytokines are analyzed. Results reveal a postnatal age-related impact of gut microbiota perturbation, with a gradual increase in the relative abundance of Proteobacteria and a reduction in Bacteroidetes and Firmicutes. Significant barrier integrity disruption, reduced TJPs and IECs marker expression, and increased systemic inflammation at P14D of AVNM-treated mice are found. Moreover, the microbiota transplantation shows recolonization of Verrucomicrobia, proving a causal role in barrier functions. The investigation reveals P14D as a critical period for neonatal intestinal development, regulated by specific microbiota composition.