Inflammatory bowel disease (IBD) is a common intermittent gastrointestinal condition and the incidence and prevalence of IBD are usually high in industrialized countries in North America and Europe. Several gut microbiome studies have been conducted in different IBD cohorts and certain specific taxonomic shifts have been associated with IBD. Although there is a relative escalation in the abundance of Enterobacteriaceae, including Escherichia coli and Fusobacterium, so far no single microbe has been demonstrated to cause IBD. It is plausible that intestinal microbiota dysbiosis may contribute to IBD pathogenesis by loss of health-promoting commensal symbionts or gain of pathobionts. We applied phosphoproteomics profiling and RNA-seq analysis in DUSP6-deficient Caco-2 cells. Our results suggested that DUSP6 could affect gut barrier functions and this is further confirmed with a dextran sulfate sodium (DSS)-induced colitis mouse model. Interestingly, with 16S rRNA gene sequencing we found that the gut/fecal microbiota in Dusp6-deficient mice was more resistant to DSS-induced dysbiosis compared with wild-type mice. In summary, these findings indicate that Dusp6-deficiency is a novel host genetic factor that could modulate gut barrier functions and mucosal immunity and inhibiting DUSP6 might be a novel strategy to shape the homeostasis of microbiota and beat IBD.
Date:
2019-05
Relation:
Journal of Immunology. 2019 May;202(1, Suppl. S):Meeting Abstract 191.8.
