An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease

We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal. In multivariable analysis of data from 613 allogeneic haematopoietic cell transplant recipients, peri-engraftment presence of O. splanchnicus was associated with ~50% lower risk for grade II–IV aGVHD (hazard ratio 0·53, 95% confidence interval 0·28–1·00, P = 0·05). O. splanchnicus may protect rs4415345G individuals against aGVHD.