A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD
M. Hanief Sofi, Yongxia Wu, Taylor Ticer, Steven Schutt, David Bastian, Hee-Jin Choi, Linlu Tian, Corey Mealer, Chen Liu, Caroline Westwater, Kent E. Armeson, Alexander V. Alekseyenko, Xue-Zhong Yu
M. Hanief Sofi, Yongxia Wu, Taylor Ticer, Steven Schutt, David Bastian, Hee-Jin Choi, Linlu Tian, Corey Mealer, Chen Liu, Caroline Westwater, Kent E. Armeson, Alexander V. Alekseyenko, Xue-Zhong Yu
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Research Article Immunology Transplantation

A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD

Abstract

Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality. The loss of diversity among intestinal bacteria caused by pretransplant conditioning regimens leads to an outgrowth of opportunistic pathogens and exacerbated GVHD after allo-HCT. Using murine models of allo-HCT, we found that an increase of Bacteroides in the intestinal microbiota of the recipients was associated with reduced GVHD in mice given fecal microbial transplantation. Administration of Bacteroides fragilis through oral gavage increased gut microbiota diversity and beneficial commensal bacteria and significantly ameliorated acute and chronic GVHD development. Preservation of gut integrity following B. fragilis exposure was likely attributed to increased short chain fatty acids, IL-22, and regulatory T cells, which in turn improved gut tight junction integrity and reduced inflammatory cytokine production of pathogenic T cells. The current study provides a proof of concept that a single strain of commensal bacteria can be a safe and effective means to protect gut integrity and ameliorate GVHD after allo-HCT.

Authors

M. Hanief Sofi, Yongxia Wu, Taylor Ticer, Steven Schutt, David Bastian, Hee-Jin Choi, Linlu Tian, Corey Mealer, Chen Liu, Caroline Westwater, Kent E. Armeson, Alexander V. Alekseyenko, Xue-Zhong Yu

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Figure 6

B. fragilis increases SCFAs in the recipient intestine after BMT.

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B. fragilis increases SCFAs in the recipient intestine after BMT. B6 BA...
B6 BALB/c BMT was initiated and B. fragilis was administered as described in Figure 3. BALB/c recipients were administered FITC-dextran by oral gavage and deprived of food and water for 4 hours on day 7 post-BMT. Peripheral blood was collected from the recipients and concentrations of FITC-dextran were measured (A). Data shown are from 2 representative experiments with each mouse sample in triplicates of 4–8 mice from each group. Three weeks after BMT, recipient ileums were collected and snap-frozen in dry ice. SCFAs were measured in intestinal tissues. The expression of different SCFAs are shown (B). The data shown here are from 1 of the 2 representative experiments with 3–4 mice from each group. The quantitative expression of different genes is shown (C). Data from 1 of the 2 representative experiments with each mouse sample in triplicates of 3–4 mice from each group. Significance is determined by 1-way ANOVA (using multiple comparison test). Asterisks indicate statistical significance *P < 0.05, **P < 0.01, **P < 0.001.