The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.
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.
Markey, KA; Schluter, J; Gomes, ALC; Littmann, ER; Pickard, AJ; Taylor, BP; Giardina, PA; Weber, D; Dai, A; Docampo, MD; Armijo, GK; Slingerland, AE; Slingerland, JB; Nichols, KB; Brereton, DG; Clurman, AG; Ramos, RJ; Rao, A; Bush, A; Bohannon, L; Covington, M; Lew, MV; Rizzieri, DA; Chao, N; Maloy, M; Cho, C; Politikos, I; Giralt, S; Taur, Y; Pamer, EG; Holler, E; Perales, M-A; Ponce, DM; Devlin, SM; Xavier, J; Sung, AD; Peled, JU; Cross, JR; van den Brink, MRM
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