Acute gastrointestinal graft-versus-host disease is associated with reductions of secondary bile acids following allogeneic hematopoietic cell transplantation.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (HCT) can cure hematologic malignancies, but 30-70% of recipients experience acute graft-versus-host disease (GvHD). GvHD is associated with perturbations in the gut microbiome. Bile acids are host derived compounds that are transformed by gut bacteria and bind to specific host cell receptors, informing our hypothesis that changes in bile acid-metabolizing gut bacteria alter bile acid levels to affect gut physiology and immunity during GvHD.

METHODS: In a longitudinal case-control study of patients with and without acute gut GvHD, we characterized bile acid concentrations and the gut microbiome in stool.

RESULTS: Primary and conjugated bile acid levels were similar regardless of gut GvHD status, but endogenous secondary bile acid concentrations were associated with gut GvHD (p = 0.009). We observed 4.4-fold lower levels of endogenous secondary bile acids in GvHD, particularly lithocholic acid and derivatives (p = 0.004/padjusted = 0.02, fold change (FC) = 0.23). There was a 100-fold lower median abundance (p = 0.002 and FC < 0.01) and 20-fold lower median diversity of bacterial bile acid 7α-dehydroxylation (bai) genes (p = 0.0007 and FC < 0.05) in patients with GvHD.

DISCUSSION: This provides evidence that acute gut GvHD patients are deficient in microbial bai genes that make secondary bile acids.