PP407 - MECHANISM OF PARABACTEROIDES DISTASONIS IN REGULATING INTESTINAL IMMUNE CELLS AND RELIEVING INFLAMMATORY BOWEL DISEASE

PP407

MECHANISM OF PARABACTEROIDES DISTASONIS IN REGULATING INTESTINAL IMMUNE CELLS AND RELIEVING INFLAMMATORY BOWEL DISEASE

M. Zhou^1,*, J. Du¹, H. Zhu¹, H. Qin^1,2

¹Shanghai Tenth People's Hospital, School of Medicine, Tongji university, Shanghai, ²Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China

Rationale: Inflammatory bowel disease is a group of chronic, nonspecific inflammatory disorders of the intestine resulting from genetic susceptibility, environmental factors, and gut microbiota dysbiosis. Parabacteroides distasonis (P.distasonis) is negatively correlated with inflammatory activity and has the ability to regulate host immunity and barrier function; however, its underlying mechanisms remain unclear.

Methods: Colon biopsy samples from human IBD patients were obtained from Shanghai Tenth People's Hospital, China. Acute colitis was induced in C57BL/6 mice by DSS and TNBS. Mice were oral administered P.distasonis therapeutically and the severity of the disease was assessed daily. Fluorescence in situ hybridization was used to detect the abundance of P.distasonis in colonic biopises of human and mice. Mouse intestinal tissue was dissociated into single-cell suspension and  stained with antibodies. 

Results: 1.By examining paired colonoscopic biopsy tissues from patients with IBD, we found that both DNA expression level and colonization density of P. distasonis were significantly lower in inflamed tissues than in matched non-inflamed tissues. Similar findings were observed in DSS/TNBS-induced mouse colitis models. 2.Oral administration of P. distasonis markedly ameliorated body weight loss, elevated disease activity index, colon shortening, and histopathological injury. 3.ScRNA-seq and flow cytometry showed that intervention with P. distasonis suppressed the ability of antigen-presenting cells to secrete IL-12/IL-23 and reduced Th17 cell differentiation and expansion.

Conclusion: P. distasonis colonization is significantly reduced in the intestines of patients with IBD compared with healthy intestines, and that exogenous supplementation with P. distasonis can alleviate disease phenotypes in DSS/TNBS-induced mouse colitis models by suppressing the IL-12/IL-23-Th17 axis.

Disclosure of Interest: None declared