Autoimmune rheumatologic diseases

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Bacterial Dysbiosis Associates with Functional Intraepithelial Lymphocyte Changes in Inflammatory Bowel Disease and Spondyloarthritis

Thursday, June 15
5:45 PM - 7:00 PM

Dysbiosis occurs in spondyloarthritis (SpA) and inflammatory bowel disease (IBD), subdivided into Crohn's Disease (CD) and Ulcerative Colitis (UC). The immunologic consequences of dysbiosis have not been defined. Intraepithelial lymphocytes (IELs) are T cells within the intestinal epithelium that are in close contact with bacteria, and as such, are likely to be modulated by dysbiosis. We correlated IELs with resident bacteria in SpA, IBD, and controls. Subjects with biopsy-proven IBD (N=10 with CD and 7 with UC), SpA fulfilling ASAS criteria (N=5), and healthy controls (N=15) were evaluated for fecal microbiome by 16S rRNA sequencing and IELs from colon biopsies analyzed by flow cytometry and ELSIA. Subjects with SpA had significantly lower numbers of IELs compared to controls (p=0.03). Subjects with CD had significantly increased IL-17A, (p=0.03) and IFN-γ (p < 0.01) whereas those with UC had higher IL-1β (p=0.01) compared to controls. Both subjects with CD and SpA had significantly increased secretion of TNF-α (p=0.04). Correlating cytokines to bacteria revealed an association between TNF-α and the Simpson Diversity Index in subjects with UC (Spearman's r=0.943, p < 0.01); in subjects with CD, Fusobacterium had a negative correlation with TNFα+IFNγ+IL-1β (Spearman's r=-0.786, p=0.02). Sequencing results from subjects with SpA are pending. Our data indicate differences in IEL function among subjects with SpA, CD, and UC compared to healthy controls. We hypothesize that the correlations between dysbiosis and IEL function are relevant to the pathogenesis of SpA and IBD. Future studies will be aimed at further understanding these mucosal T cell and microbial interactions.

Neha Ohri

Assistant Professor
Mount Sinai Hospital

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    Mark E. Gerich

    University of Colorado, Anschutz Medical Campus

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      Blair P. Fennimore

      University of Colorado, Anschutz Medical Campus

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        Diana Ir

        University of Colorado, Anschutz Medical Campus

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          Charles E. Robertson

          University of Colorado, Anschutz Medical Campus

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            Emilie Regener

            University of Colorado, Anschutz Medical Campus

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              Liron Caplan

              University of Colorado, Anschutz Medical Campus

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                Brandie D. Wagner

                University of Colorado, Anschutz Medical Campus

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                  Daniel Frank

                  University of Colorado, Anschutz Medical Campus

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                    Kristine A. Kuhn

                    Assistant Professor
                    University of Colorado, Anschutz Medical Campus

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