Faculty, Staff and Student Publications

Publication Date

9-11-2024

Journal

Cell Host & Microbe

DOI

10.1016/j.chom.2024.08.004

PMID

39214085

PMCID

PMC11441101

PubMedCentral® Posted Date

9-11-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Keywords

Graft vs Host Disease, Animals, Bacteroides, Gastrointestinal Microbiome, Mice, Humans, Female, Male, Dysbiosis, Feces, Hematopoietic Stem Cell Transplantation, Disease Models, Animal, Mice, Inbred C57BL, Middle Aged, Akkermansia, Adult, Bacteroides thetaiotaomicron, Mice, Inbred BALB C, Bacteroides ovatus, Bacteroides thetaiotaomicron, Akkermansia muciniphila, allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, intestinal microbiome, mucus layer, xylose, polysaccharides, polysaccharide utilization loci

Published Open-Access

yes

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