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

   


Authors: Hayase, E.; Hayase, T.; Mukherjee, A.; Stinson, S. C.; Jamal, M. A.; Ortega, M. R.; Sanchez, C. A.; Ahmed, S. S.; Karmouch, J. L.; Chang, C. C.; Flores, I. I.; McDaniel, L. K.; Brown, A. N.; El-Himri, R. K.; Chapa, V. A.; Tan, L.; Tran, B. Q.; Xiao, Y.; Fan, C.; Pham, D.; Halsey, T. M.; Jin, Y.; Tsai, W. B.; Prasad, R.; Glover, I. K.; Enkhbayar, A.; Mohammed, A.; Schmiester, M.; King, K. Y.; Britton, R. A.; Reddy, P.; Wong, M. C.; Ajami, N. J.; Wargo, J. A.; Shelburne, S.; Okhuysen, P. C.; Liu, C.; Fowler, S. W.; Conner, M. E.; Katsamakis, Z.; Smith, N.; Burgos da Silva, M.; Ponce, D. M.; Peled, J. U.; van den Brink, M. R. M.; Peterson, C. B.; Rondon, G.; Molldrem, J. J.; Champlin, R. E.; Shpall, E. J.; Lorenzi, P. L.; Mehta, R. S.; Martens, E. C.; Alousi, A. M.; Jenq, R. R.
Article Title: Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease
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. Copyright © 2024 Elsevier Inc. All rights reserved.
Keywords: adult; middle aged; mouse; animal; animals; mice; hematopoietic stem cell transplantation; drug effect; mice, inbred balb c; mice, inbred c57bl; c57bl mouse; disease model; bagg albino mouse; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; disease models, animal; intestine flora; microbiology; graft vs host disease; polysaccharides; feces; graft-versus-host disease; bacteroides; humans; human; male; female; dysbiosis; intestinal microbiome; gastrointestinal microbiome; akkermansia muciniphila; xylose; polysaccharide utilization loci; bacteroides thetaiotaomicron; akkermansia; bacteroides ovatus; mucus layer
Journal Title: Cell Host & Microbe
Volume: 32
Issue: 9
ISSN: 1931-3128
Publisher: Cell Press  
Date Published: 2024-01-01
Start Page: 1621
End Page: 1636
Language: English
DOI: 10.1016/j.chom.2024.08.004
PUBMED: 39214085
PROVIDER: scopus
PMCID: PMC11441101
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85204165933&doi=10.1016%2fj.chom.2024.08.004&partnerID=40&md5=985468cebe564bb7c6b866d56fafbf4d
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK staff member Alan Hanash is thanked in the acknowledgements "... for serving as external advisory committeemember[s] of this work." -- Source: Scopus
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Doris Ponce
    256 Ponce
  3. Jonathan U Peled
    155 Peled
  4. Marina Burgos da Silva
    26 Burgos da Silva
  5. Zoe Katsamakis
    4 Katsamakis
  6. Natalie Grier Smith
    2 Smith
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