Sofi MH(1), Wu Y(1), Ticer T(1), Schutt S(1), Bastian D(1), Choi HJ(1), Tian L(1), Mealer C(1), Liu C(2), Westwater C(1)(3), Armeson KE(4), Alekseyenko AV(3)(4), Yu XZ(1). Author information:
(1)Department of Microbiology and Immunology, Hollings Cancer Center, College of
Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
(2)Department of Pathology, Yale School of Medicine, New Haven, Connecticut,
(3)Department of Oral Health Sciences, College of Dental Medicine, Medical
University of South Carolina, Charleston, South Carolina, USA.
(4)Biomedical Informatics Center and Department of Public Health Sciences,
College of Medicine, and Department of Healthcare Leadership & Management,
College of Public Health Sciences, Medical University of South Carolina,
Charleston, South Carolina, USA.
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.
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