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* = Presenting author

P019 Anti-TNF-alpha therapy induces microbial and immunological changes in dextran sodium sulphate chronic colitis

Petito V.*1, Graziani C.1, Lopetuso L.1, Quaranta G.2, Paroni Sterbini F.2, Masucci L.2, Sgambato A.3, Cammarota G.1, Sanguinetti M.2, Gasbarrini A.1, Scaldaferri F.1

1Fondazione Policlinico Universitario Gemelli, Catholic University of Sacred Heart, Gastroenterological Area, Gastroenterological and Endocrino-Metabolical Sciences Department, ROME, Italy 2Catholic University of Sacread Hearth, “A. Gemelli” Hospital, Department of Microbiology, Rome, Italy 3Catholic University of Sacred Heart of Rome, Department of Pathology, Rome, Italy

Background

Anti-TNF alpha represent the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe Ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNF-alpha therapy and this role in mucosal healing. Evaluate gut microbiota changes and adaptive immune system response to anti TNF-alpha therapy in murine DSS colitis.

Methods

C57BL/6 mice were fed for 5 days with 3% Dextransodium sulphate (DSS) in drinking water. At day 3 of DSS treatment, a group of mice received intravenous administration of infliximab (IFX) (5 mg/Kg) or placebo. Further 2 groups of mice received IFX or placebo without DSS. Disease severity was scored daily using the four points Disease Activity Index (DAI). At the moment of sacrifice, serum, colon, feces and mesenteric lymph node (MLN) were collected from each animal. Bacillus fragilis, Clostridium scindens, Fecalibacterium prausnitzii and Escherichia coli were assessed by qPCR, following bacterial DNA extraction from feces.

Results

Anti- inflammatory species increased in fecal samples of colitis mice trated by IFX, compared to control mice, and in particular B. fragilis, F. prausnitzii and C. scindens. Furthermore, in colitic mice treated with IFX, microbial changes are associated to an initial increase (day 5 of the colitis) in T reg cells and Th1 cells, followed by a consequent decrease (day 14 of the colitis) in Treg, Th1, Th2 and Th17. Similar results, with different absolute values, were found in mice treated with IFX in absence of DSS induced colitis.

Conclusion

IFX therapy is associated with measurable microbial and immune cells changes in DSS colitis. These preliminary data open the scenario to the possibility that the translocation of microbial products, especially from anti-inflammatory species, could influenced the plasticity of T cells from Th1 to iT regs. Further analysis on immune cells within mucosa will be necessary.