# Microbiota-derived short-chain fatty acids in hematopoietic stem cell transplantation: immunomodulation at the host-microbiota interface

## TL;DR

This review explores how gut microbiota-produced short-chain fatty acids, like butyrate, can help improve outcomes in hematopoietic stem cell transplantation by supporting immune recovery and reducing complications.

## Contribution

The paper reviews the role of microbiota-derived short-chain fatty acids in modulating immunity during hematopoietic stem cell transplantation and highlights potential therapeutic strategies.

## Key findings

- Short-chain fatty acids (SCFAs) help maintain gut barrier function and regulate immune responses after transplantation.
- Transplant-related disruptions in gut microbiota reduce SCFA availability, contributing to immune imbalance.
- Strategies to enhance SCFA production, such as dietary fiber or probiotics, may improve transplant outcomes.

## Abstract

Hematopoietic stem cell transplantation (HSCT) remains a cornerstone treatment for many hematological malignancies, but its clinical success is still challenged by graft-vs.-host disease (GvHD), infectious complications, and the profound microbial disruptions caused by conditioning, antibiotics, and hospitalization. Over the past few years, a growing body of work has highlighted how tightly post-transplant immunity is linked to the state of the gut microbiota. In particular, short-chain fatty acids (SCFAs), especially butyrate, have emerged as key microbial metabolites involved in maintaining epithelial barrier function, moderating inflammatory responses, and supporting regulatory T-cell homeostasis. In this review, we bring together current evidence on the SCFA-gut-immune axis in the setting of HSCT, with a focus on how transplant-related dysbiosis alters SCFA availability and contributes to immune imbalance. We also discuss the potential of strategies designed to restore or enhance SCFA production, ranging from dietary fiber interventions to next-generation probiotics and other microbiota-directed approaches. Overall, by better understanding and eventually harnessing the metabolic capacity of the gut microbiota, SCFA-centered therapies may offer new opportunities to support immune recovery, reduce GvHD risk, and improve outcomes for HSCT recipients. Still, well-designed clinical trials are needed to determine how these approaches can be safely and effectively integrated into transplant care.

Diagram illustrating the role of short-chain fatty acids (SCFAs) in hematopoietic stem cell transplantation (HSCT). SCFAs, derived from dietary fiber by gut microbiota, enhance post-transplant outcomes. Arrows indicate the formation of SCFAs from fiber, their absorption, and the positive impact on transplantation success.