Microbiota Dynamics in Hematopoietic Stem Cell Transplantation

The process of allogeneic haematopoietic stem cell transplantation (HCT) entails profound alterations in the gut microbiome, which in turn influence engraftment, immune reconstitution and clinical outcomes. Conditioning regimens such as chemotherapy and radiotherapy disrupt commensal communities, precipitating dysbiosis characterised by loss of beneficial taxa and expansion of opportunistic pathogens. This imbalance elevates the risk of graft-versus-host disease (GVHD), bloodstream infections and Clostridioides difficile infection. Conversely, a resilient and diverse microbiota fosters production of short-chain fatty acids (SCFAs), fortifies intestinal barrier integrity and modulates systemic immunity through metabolite-driven signalling. Interventions aimed at restoring homeostasis include dietary modulation, microbial metabolite supplementation, targeted bacteriophage enzymes and faecal microbiota transplantation (FMT). Recent advances have elucidated mechanisms by which specific bacterial species or their metabolites regulate haematopoiesis, temper alloreactive T-cell responses and protect against invasive infection. An integrated understanding of microbial ecology and host responses is guiding novel prophylactic and therapeutic strategies to improve transplant success and patient survival.

Research from Nature Portfolio

Recent studies have demonstrated that administration of a bacteriophage-derived enzyme effectively disrupts biofilms formed by pathogenic Enterococcus faecalis in the intestinal tract of transplantation recipients, curbing proliferation of cytolysin-positive strains and mitigating the severity of acute GVHD in preclinical models. In parallel, a feasibility trial of dietary intervention with resistant potato starch revealed that sustained supplementation from pre-transplant through engraftment is achievable in clinical settings and significantly elevates faecal butyrate concentrations. This intervention stabilised key plasma metabolites during early post-transplantation, suggesting that dietary modulation of microbial fermentation can support metabolic resilience and may attenuate inflammatory complications following HCT.

Microbiota Dynamics in Hematopoietic Stem Cell Transplantation publication trend

The graph below shows the total number of articles in microbiota dynamics in hematopoietic stem cell transplantation across all publications each year (not limited to Nature Index journals).

Technical terms

Allogeneic haematopoietic stem cell transplantation (HCT): Transfer of blood-forming stem cells from a genetically matched donor to a recipient, following myeloablative or reduced-intensity conditioning.

Graft-versus-host disease (GVHD): Immune-mediated tissue damage in the recipient caused by donor T cells recognising host antigens as foreign.

Dysbiosis: Disruption of the normal microbiota characterised by reduced diversity and imbalance between beneficial and pathogenic microorganisms.

Short-chain fatty acids (SCFAs): Metabolic by-products of microbial fermentation of dietary fibres, notably acetate, propionate and butyrate, with immunomodulatory and barrier-protective functions.

Biofilm: Structured community of bacteria embedded in a self-produced extracellular matrix, often conferring resistance to antimicrobials.

Faecal microbiota transplantation (FMT): Transfer of processed stool from a healthy donor into the gastrointestinal tract of a patient to restore microbial balance.

References

1. An enterococcal phage-derived enzyme suppresses graft-versus-host disease. Nature (2024).
2. Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation. Nature Medicine (2023).
3. Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection. Genome Medicine (2016).
4. Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study. Frontiers in Immunology (2018).
5. Protective Factors in the Intestinal Microbiome Against Clostridium difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation. The Journal of Infectious Diseases (2017).