Fecal microbiota transplantation (FMT) is an emerging microbiome-based approach being studied for patients with gastrointestinal graft-versus-host disease (GI-GVHD), particularly when the disease does not respond adequately to standard treatment.

After an allogeneic hematopoietic stem cell transplant, changes in the intestinal microbiome can contribute to inflammation and disruption of the gut barrier. FMT aims to restore a healthier and more diverse community of intestinal microorganisms. Current evidence suggests potential benefit in selected patients with steroid-refractory or steroid-dependent GI-GVHD, although the treatment remains an area of active clinical research.

What Is Graft-Versus-Host Disease?

Graft-versus-host disease occurs when immune cells from a donor attack tissues in the transplant recipient.

It is a potential complication of allogeneic stem cell transplantation and can affect several organs, including:

• Skin

• Liver

• Gastrointestinal tract

When GVHD affects the gastrointestinal tract, patients may develop symptoms such as diarrhea, abdominal pain, nausea, vomiting, and difficulty maintaining adequate nutrition.

What Is Refractory GVHD?

GVHD is considered refractory when it does not respond adequately to standard treatment.

For acute GVHD, corticosteroids are commonly used as initial therapy. Some patients, however, have persistent or worsening gastrointestinal disease despite treatment.

These patients may require additional immunosuppressive or targeted therapies. FMT is being investigated as one potential microbiome-directed approach for selected patients with refractory GI-GVHD.

The Gut Microbiome and GVHD

The intestine contains a complex community of microorganisms collectively known as the gut microbiome.

Chemotherapy, conditioning treatment, antibiotics, transplantation, and immunosuppressive medicines can disrupt this microbial ecosystem.

This disruption, known as dysbiosis, may be associated with:

• Reduced microbial diversity

• Loss of beneficial bacterial populations

• Increased intestinal inflammation

• Impaired gut-barrier function

• Changes in immune regulation

The relationship between intestinal microbiota and GVHD is an active area of research. Restoring microbial diversity may help influence intestinal inflammation and immune responses.

How Does Fecal Microbiota Transplantation Work?

FMT involves transferring processed intestinal microbiota from a carefully screened donor into the gastrointestinal tract of the recipient.

The objective is to introduce a diverse microbial community that may help restore the recipient's disrupted gut microbiome.

Depending on the treatment protocol, FMT may be administered through routes such as:

• Oral capsules

• Upper gastrointestinal administration

• Colonoscopy

• Other gastrointestinal delivery methods

The optimal route, dose, frequency, and donor characteristics for GVHD are not yet standardised. Studies have used different protocols, contributing to variability in reported outcomes.

Who May Be Considered for FMT?

FMT has primarily been studied in patients with gastrointestinal GVHD, particularly those with steroid-refractory or steroid-dependent disease.

Potential candidates require careful clinical assessment, including consideration of:

• Type and severity of GVHD

• Gastrointestinal involvement

• Response to standard treatment

• Infection status

• Immune status

• Current immunosuppressive therapy

• Overall clinical condition

FMT should not be viewed as a replacement for established GVHD treatment. Its use in this setting requires specialist assessment and appropriate donor screening and infection-control procedures.

What Does the Evidence Show?

Early studies have reported encouraging responses in patients with refractory GVHD.

A 2023 systematic review and meta-analysis involving 242 patients with steroid-resistant or steroid-dependent GVHD reported complete responses in 100 patients and partial responses in 61 patients. However, the evidence included prospective and retrospective single-arm studies, case series, and case reports, so the results cannot establish the same level of certainty as large randomised controlled trials.

More recent evidence continues to suggest potential benefit, particularly in gastrointestinal GVHD. A 2026 systematic review of 20 studies found that responses in GVHD were variable, with median complete-response and overall-response rates around 50% to 55% in steroid-refractory cases. The authors also highlighted substantial differences between studies in patient selection, FMT protocols, and outcome assessment.

A 2026 meta-analysis of six studies involving 262 patients found higher short-term clinical and complete-response rates for FMT in GI-GVHD compared with conventional treatment groups. However, the authors concluded that further research is needed to define its role and that the evidence does not establish FMT as a standard treatment for GVHD prevention.

Potential Benefits of FMT

The proposed benefits of FMT in GVHD include:

• Restoration of gut microbial diversity

• Reintroduction of beneficial bacterial populations

• Potential improvement in intestinal barrier function

• Modulation of inflammatory and immune responses

• Potential improvement in gastrointestinal GVHD symptoms

Studies have reported increases in certain bacterial groups following FMT, including Bacteroides and Bifidobacterium.

Safety Considerations

Patients who have undergone allogeneic stem cell transplantation are often significantly immunocompromised. This makes infection prevention particularly important.

Potential concerns with FMT include transmission of infectious organisms from the donor and complications related to gastrointestinal administration.

For this reason, donor screening and microbiological testing are critical. The safety profile also needs to be considered in the context of the patient's immune status, active infections, and concurrent treatment.

Recent reviews have reported predominantly mild gastrointestinal adverse events in published studies, but the available evidence remains limited and heterogeneous.

FMT Is Not the Same as Conventional GVHD Treatment

FMT works through a different mechanism from conventional immunosuppressive treatment.

Standard GVHD management may involve corticosteroids and other immunosuppressive or targeted therapies depending on disease severity and response.

FMT aims to modify the intestinal microbiome rather than directly suppress the immune system.

It is therefore being explored as a complementary or salvage strategy in selected patients rather than as a universal replacement for established GVHD therapies.

The Future of Microbiome-Based Treatment

Research into the relationship between the gut microbiome and GVHD is rapidly evolving.

Future approaches may include:

• More precisely selected donor microbiota

• Defined microbial consortia

• Microbiome-derived therapeutics

• Personalised microbiome profiling

• Combination approaches with conventional GVHD therapies

The goal is to develop safer and more predictable ways of restoring intestinal microbial balance after transplantation.

Conclusion

Fecal microbiota transplantation represents an emerging approach for selected patients with refractory gastrointestinal graft-versus-host disease following allogeneic stem cell transplantation.

By attempting to restore the intestinal microbiome, FMT may influence gut-barrier function, inflammation, and immune regulation. Early studies and recent systematic reviews have reported encouraging responses, particularly in steroid-refractory GI-GVHD. However, differences between studies and the limited number of high-quality prospective trials mean that its precise role, optimal timing, administration method, and patient selection continue to be investigated.

For patients with refractory GVHD, FMT should be considered only within an appropriate specialist transplant program and after careful assessment of potential benefits, risks, and available standard treatment options.