612 Characterization of Intestinal Microbiome in Diarrhea-Predominant Irritable Bowel Syndrome, Depression Patients and Their Comorbidity

Abstract

cytokine production was assessed by LMA on cell supernatants. Results: With chronic Hp infection, there was decreased total gastritis in Egfr∆mye mice (p<0.001) versus Egfr or LysM mice. Chronic and acute gastritis scores were significantly decreased in Egfr∆mye mice. Hp colonization was significantly higher, a 1.4 log-order increase, in Egfr∆mye mice (p<0.001) vs. the Egfr and LysM controls. Consistent with these findings, mRNA levels of M1 polarization genes (iNOS, TNFα, IL-1β; p<0.05) were decreased in gastric tissues from Egfr∆mye vs. control mice. iNOS was also decreased (p<0.05) at the protein level in infiltrating Gmacs in Egfr∆mye mice. Mreg gene expression (IL-10, TGF-β, LIGHT; p<0.05) was also decreased in the tissues of Egfr∆mye mice. Levels of pro-inflammatory cytokines/chemokines (KC, IP-10, RANTES; p<0.005; G-CSF, MIG, MIP-1 α, MIP-1β, IL17; p<0.05) were significantly decreased in tissues from Egfr∆mye mice. Splenic T-cells from Egfr∆mye mice produced less IFN-γ and IL-2 (p<0.05) indicative of a diminished Th1 response. IL-4 and IL-5 levels were equivalent between genotypes, indicating Th2 responses remained unchanged. Gmac infiltration was not altered in Egfr∆mye vs. Egfr mice. Conclusions: EGFR acts as a master regulator of M Φ polarization and function in vivo. Our findings indicate that MΦ EGFR signaling promotes control of Hp infection by increasing M1 polarization and the downstream Th1 response. However, this scenario also enhances gastritis and thus may contribute to gastric carcinogenesis.