Shotgun metagenomic sequencing of the fecal microbiome to predict response to frontline high-dose steroids in patients with lower gastrointestinal acute graft-versus-host disease

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) recipients. High-dose steroids are the conventional frontline treatment for aGVHD. Because steroid- refractory aGVHD, esp. lower gastrointestinal (LGI) aGVHD, has a dismal prognosis, early identification of patients unlikely to respond to frontline treatment is of critical importance and highlights a target population for novel therapeutics. Specifically, biomarkers of treatment refractoriness, if found before the onset of aGVHD, would potentially guide monitoring and preparation for high-risk disease in the following days to weeks. We report an exploratory analysis using shotgun metagenomic sequencing to evaluate whether gut microbiota changes before LGI aGVHD onset are predictive of response to frontline high-dose steroids.