The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.

Abstract

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.

• Authors: Kate A Markey, Jonas Schluter, Antonio L C Gomes, Eric R Littmann, Amanda J Pickard, Bradford P Taylor, Paul A Giardina, Daniela Weber, Anqi Dai, Melissa D Docampo, Gabriel K Armijo, Ann E Slingerland, John B Slingerland, Katherine B Nichols, Daniel G Brereton, Annelie G Clurman, Ruben J Ramos, Arka Rao, Amy Bush, Lauren Bohannon, Megan Covington, Meagan V Lew, David A Rizzieri, Nelson Chao, Molly Maloy, Christina Cho, Ioannis Politikos, Sergio Giralt, Ying Taur, Eric G Pamer, Ernst Holler, Miguel-Angel Perales, Doris M Ponce, Sean M Devlin, Joao Xavier, Anthony D Sung, Jonathan U Peled, Justin R Cross, Marcel R M van den Brink
• Journal: Blood (Blood) Vol. 136 Issue 1 Pg. 130-136 (07 02 2020) ISSN: 1528-0020 [Electronic] United States
• PMID: 32430495 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by The American Society of Hematology.

Chemical References

• Butyrates
• Propionates

Topics

• Adult
• Allografts
• Bacteria (isolation & purification, metabolism)
• Butyrates (blood)
• Case-Control Studies
• Chronic Disease
• Dysbiosis (etiology, microbiology)
• Feces (microbiology)
• Gastrointestinal Microbiome
• Graft vs Host Disease (blood, etiology, microbiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Metabolome
• Propionates (blood)
• Ribotyping