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

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 allo-HSCT patient stool (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 enZyme (CAZyme) and found that Parabacteroides merdae, Parabacteroides distasonis and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop LGI-GVHD compared to those who did. The specific gene abundances of xylosidase, which contribute to the degradation of xylose-containing polysaccharides, were significantly associated with reduced risk of LGI-GVHD. Together, these findings show the importance of carbohydrate degrading functionality of putative beneficial bacteria in mediating risk of LGI-GVHD.