Multi-omics unravel the compromised mucosal barrier function linked to aberrant mucin O-glycans in a pig model

Early weaning stress (EWS) in piglets is associated with intestinal dysfunction. Here, utilizing a pig EWS model to mimic early-life stress (ELS) in humans, we investigated the mechanism of ELS-induced intestinal diseases through integrated multi-omics analyses of proteome, glycome, and microbiome. Our results demonstrated that EWS resulted in disrupted the ileal barrier integrity by reducing tight junction-related gene expression and interfering with cell-cell adhesion paralleled the increased proportion of pathogens such as Escherichia_Shigella and Helicobacter. Furthermore, Proteome data revealed that the accumulation of unfolded proteins and insufficient unfolded protein response (UPR) process caused by EWS led to ER stress. Data from proteome and glycome found that EWS induced aberrant mucin O-glycans, including truncated glycans, reduction in acidic glycans, and increased in fucosylated glycans. In addition, correlation test by taking fucose and inflammatory response into account suggested that enhancement of fucose expression might be a compensatory host response. Taken together, these results extend the comprehensive knowledge of the detrimental impacts and pathogenesis of EWS and help to provide intervention targets for ELS-induced intestinal diseases in the future.

Automated summary

This study investigated the mechanism of early-life stress (ELS)-induced intestinal diseases using a pig early weaning stress (EWS) model. The results showed that EWS disrupted ileal barrier integrity, leading to increased proportion of pathogens and unfolded protein response (UPR) process. Aberrant mucin O-glycans were also induced by EWS. The findings contribute to a comprehensive understanding of EWS and provide intervention targets for ELS-induced intestinal diseases.