Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease

Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C. Stinson, Mohamed A. Jamal, Miriam R. Ortega, Christopher A. Sanchez, Saira S. Ahmed, Jennifer L. Karmouch, Chia Chi Chang, Ivonne I. Flores, Lauren K. McDaniel, Alexandria N. Brown, Rawan K. El-Himri, Valerie A. Chapa, Lin Tan, Bao Q. Tran, Yao Xiao, Christopher Fan, Dung PhamTaylor M. Halsey, Yimei Jin, Wen Bin Tsai, Rishika Prasad, Israel K. Glover, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Katherine Y. King, Robert A. Britton, Pavan Reddy, Matthew C. Wong, Nadim J. Ajami, Jennifer A. Wargo, Samuel Shelburne, Pablo C. Okhuysen, Chen Liu, Stephanie W. Fowler, Margaret E. Conner, Zoe Katsamakis, Natalie Smith, Marina Burgos da Silva, Doris M. Ponce, Jonathan U. Peled, Marcel R.M. van den Brink, Christine B. Peterson, Gabriela Rondon, Jeffrey J. Molldrem, Richard E. Champlin, Elizabeth J. Shpall, Philip L. Lorenzi, Rohtesh S. Mehta, Eric C. Martens, Amin M. Alousi, Robert R. Jenq

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1621-1636.e6
JournalCell Host and Microbe
Volume32
Issue number9
DOIs
StatePublished - Sep 11 2024

Keywords

  • Akkermansia muciniphila
  • Bacteroides ovatus
  • Bacteroides thetaiotaomicron
  • allogeneic hematopoietic stem cell transplantation
  • graft-versus-host disease
  • intestinal microbiome
  • mucus layer
  • polysaccharide utilization loci
  • polysaccharides
  • xylose

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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