Fecal carbohydrate-degrading bacteria are associated with reduced incidence of lower gastrointestinal GVHD

ABSTRACT: Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop LGI-GVHD compared with those who did. The specific gene abundances of xylosidase, which contribute to the degradation of xylose-containing polysaccharides, were significantly associated with a reduced risk of LGI-GVHD. All these findings show the importance of the carbohydrate-degrading functionality of putative beneficial bacteria in mediating risk of LGI-GVHD.