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 (SCFA) 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 was available - rather than plasma - and the differences in SCFA observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort, and one of two 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 short chain fatty acids.