Oral Sodium Butyrate Supplementation, Gut Microbiome Modulation, and Reduced Acute Graft-Versus-Host Disease After...

Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Disruption of the gut microbiome during transplantation has been implicated in the pathogenesis of aGVHD, yet clinically applicable strategies to modulate the microbiome in immunocompromised patients remain limited. To evaluate the association between oral sodium butyrate supplementation and the incidence and severity of aGVHD, and to investigate its impact on gut microbiome recovery following allo-HSCT. In this prospective, single-center study, 39 consecutive patients undergoing allo-HSCT received oral sodium butyrate (1200 mg/d) from neutrophil engraftment to day +100. Outcomes were compared with 18 historical controls treated at the same institution without butyrate supplementation. The primary endpoint was the cumulative incidence of grade II to IV aGVHD by day +100. Secondary endpoints included lower gastrointestinal aGVHD and microbiome characteristics assessed using shotgun metagenomic sequencing. Competing risk analyses were performed to account for death as a competing event. Butyrate supplementation was associated with a lower incidence of grade II to IV aGVHD (30% versus 53%, P = .028) and grade III to IV aGVHD (5% versus 34%, P = .002). Lower gastrointestinal aGVHD occurred in 5% of the butyrate group compared with 40% of historical controls (P < .001). In multivariable competing risk analysis, butyrate supplementation remained independently associated with reduced grade II to IV aGVHD (adjusted HR: 0.31, 95% CI: 0.11 to 0.89; P = .029) and lower gastrointestinal aGVHD (adjusted HR: 0.07, 95% CI: 0.02 to 0.30; P < .001). Microbiome analysis demonstrated improved recovery of gut microbial diversity at day +100 in the butyrate group, with enrichment of commensal taxa and restoration of fecal butyrate levels. Oral sodium butyrate supplementation was associated with reduced incidence and severity of aGVHD, particularly involving the gastrointestinal tract, along with improved microbiome recovery. These findings suggest a potential role for postbiotic-based microbiome modulation in GVHD prevention and warrant validation in randomized controlled trials.