Fecal microbiota transplantation enhances gut microbial diversity and metabolic functional potential in a pediatric allo-HCT recipient with steroid-refractory GvHD

Abstract

Abstract Fecal microbiota transplantation (FMT) is a promising strategy to restore gut microbial diversity and functional potential after hematopoietic stem cell transplantation (HCT). To characterize microbiome and functional changes after FMT in a pediatric HCT recipient with steroid-refractory GvHD. Detailed single-patient case study of a pediatric HCT recipient with refractory graft-versus-host disease who underwent FMT 224 days post-transplantation. Shotgun metagenomics after FMT profiled alpha diversity, species-level composition, and longitudinal changes in gut metabolic modules, including carbohydrate, amino-acid, and mucin degradation and anaerobic energy metabolism. Before FMT, the patient had lower alpha diversity than pediatric HCT controls. FMT induced a rapid, marked increase in diversity that mirrored the donor material. A two-shot FMT scheme produced a more sustained effect, with elevated diversity persisting for several days post-infusion. Species-level analyses showed post-FMT increases in taxa of potential functional interest, including Roseburia intestinalis and Lactobacillus gasseri, whereas potentially opportunistic taxa, including Escherichia coli, displayed transient blooms around infectious episodes. Functional assessments indicated that several gut metabolic modules enriched in the donor material also increased in the recipient following FMT, consistent with increased functional potential. In our single case study, FMT was followed by increased gut microbial diversity and functional potential in a pediatric HCT recipient with refractory GvHD. The sustained alpha-diversity gains with a two-shot scheme support this dosing approach, while the infection-linked fluctuations highlight the need for strategies that enhance the durability and resilience of FMT outcomes in the face of infectious challenges.