In the Journals

Fecal transplant may restore gut microbiota after bone marrow transplantation

Autologous fecal microbiota transplantation appeared safe and effective in a small cohort of patients with cancer who received microbiota-depleting antibiotics during allogeneic hematopoietic stem cell transplantation, according to results of an open-label, randomized trial published in Science Translational Medicine.

“This important study suggests that clinical intervention using autologous fecal microbiota transplantation can safely reverse the disruptive effects of broad-spectrum antibiotic treatment,” Anthony S. Fauci, MD, director of NIH’s National Institute of Allergy and Infectious Diseases, who was not involved in the study, said in a press release. “If validated in larger studies, this approach may prove to be a relatively simple way to quickly restore a person’s healthy microbiome following intensive antimicrobial therapy.”

Patients who undergo allogeneic HSCT receive antibiotics to prevent infection associated with transplant. Consequently, antibiotics decrease beneficial gut microbiota that inhibit pathogens and promote immune defense. This increases the risk for adverse events, including infection and graft-versus-host disease, according to study background.

The single-center trial included 25 patients with cancer undergoing allogeneic HSCT. Evaluable patients provided stool samples prior to and within 14 days of randomization.

To determine the feasibility, safety and efficacy of autologous fecal microbiota transplantation (auto-FMT) for reconstitution of gut microbiota, investigators sought to compare outcomes among 14 patients randomly assigned to auto-FMT vs. 11 patients assigned to standard of care.

Clostridium difficile infection, evaluated 1 year after randomization, served as the primary endpoint. Secondary end points included systemic and intestinal bacterial and viral infections and GVHD.

Results showed a significant increase in microbiota diversity among patients who underwent auto-FMT (P < .0001). The inverse Simpson index increased by an average of 63.8% (95% CI, 36.3-91.2) in addition to the baseline increase of 38.7% (95% CI, 17.9-59.6) observed in those who did not undergo auto-FMT. In addition, patients’ personal gut microbiota components were restored with auto-FMT (P < .0001).

To control for effects of dietary intake, investigators pooled longitudinal data on diet by randomization (eating, fasting or on a low dietary intake) and obtained data on granulocyte colony-stimulating factor (G-CSF) treatment.

Results of a reworked mixed-effects model including dietary intake and G-CSF administration as time-dependent covariates confirmed the beneficial effect of auto-FMT on increasing gut microbiota diversity (P < .001) and recovering original gut microbiota composition (P < .001).

“These results demonstrate the potential for fecal sample banking and post-treatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment during allogeneic HSCT,” the researchers wrote.

Limitations of the study include its single-institution nature and that auto-FMT samples may have been derived from patients who were treated for cancer and exposed to antibiotics, and therefore may be depleted of some commensal bacterial species.

The study is ongoing, and researchers continue to monitor patients to assess improvements in outcomes with auto-FMT, including the incidence and severity of bacterial, viral and fungal infections and graft-versus-host disease. – by Jennifer Southall

Disclosures: Please see the study for all authors’ relevant financial disclosures.

 

 

Autologous fecal microbiota transplantation appeared safe and effective in a small cohort of patients with cancer who received microbiota-depleting antibiotics during allogeneic hematopoietic stem cell transplantation, according to results of an open-label, randomized trial published in Science Translational Medicine.

“This important study suggests that clinical intervention using autologous fecal microbiota transplantation can safely reverse the disruptive effects of broad-spectrum antibiotic treatment,” Anthony S. Fauci, MD, director of NIH’s National Institute of Allergy and Infectious Diseases, who was not involved in the study, said in a press release. “If validated in larger studies, this approach may prove to be a relatively simple way to quickly restore a person’s healthy microbiome following intensive antimicrobial therapy.”

Patients who undergo allogeneic HSCT receive antibiotics to prevent infection associated with transplant. Consequently, antibiotics decrease beneficial gut microbiota that inhibit pathogens and promote immune defense. This increases the risk for adverse events, including infection and graft-versus-host disease, according to study background.

The single-center trial included 25 patients with cancer undergoing allogeneic HSCT. Evaluable patients provided stool samples prior to and within 14 days of randomization.

To determine the feasibility, safety and efficacy of autologous fecal microbiota transplantation (auto-FMT) for reconstitution of gut microbiota, investigators sought to compare outcomes among 14 patients randomly assigned to auto-FMT vs. 11 patients assigned to standard of care.

Clostridium difficile infection, evaluated 1 year after randomization, served as the primary endpoint. Secondary end points included systemic and intestinal bacterial and viral infections and GVHD.

Results showed a significant increase in microbiota diversity among patients who underwent auto-FMT (P < .0001). The inverse Simpson index increased by an average of 63.8% (95% CI, 36.3-91.2) in addition to the baseline increase of 38.7% (95% CI, 17.9-59.6) observed in those who did not undergo auto-FMT. In addition, patients’ personal gut microbiota components were restored with auto-FMT (P < .0001).

To control for effects of dietary intake, investigators pooled longitudinal data on diet by randomization (eating, fasting or on a low dietary intake) and obtained data on granulocyte colony-stimulating factor (G-CSF) treatment.

Results of a reworked mixed-effects model including dietary intake and G-CSF administration as time-dependent covariates confirmed the beneficial effect of auto-FMT on increasing gut microbiota diversity (P < .001) and recovering original gut microbiota composition (P < .001).

“These results demonstrate the potential for fecal sample banking and post-treatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment during allogeneic HSCT,” the researchers wrote.

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Limitations of the study include its single-institution nature and that auto-FMT samples may have been derived from patients who were treated for cancer and exposed to antibiotics, and therefore may be depleted of some commensal bacterial species.

The study is ongoing, and researchers continue to monitor patients to assess improvements in outcomes with auto-FMT, including the incidence and severity of bacterial, viral and fungal infections and graft-versus-host disease. – by Jennifer Southall

Disclosures: Please see the study for all authors’ relevant financial disclosures.