Related Experiment Video
Updated: Sep 28, 2025
Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-Deficient Mouse Model
Published on: April 6, 2022
Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient
Patricia P Bloom1, John Donlan2, Mariam Torres Soto3
11259Division of GastroenterologyUniversity of MichiganAnn ArborMichiganUSA.
Abstract:
Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).
Insights
Fecal microbiota transplant (FMT) capsules improved cognition in patients with hepatic encephalopathy (HE). Cognitive improvements varied by donor and recipient factors, with specific Bifidobacterium species linked to better outcomes.
Area of Science:
- Gastroenterology and Hepatology
- Microbiome Research
- Neurology
Background:
- Hepatic encephalopathy (HE) is a serious complication of liver disease.
- Fecal microbiota transplant (FMT) shows potential for treating HE, but donor and recipient factors are not well understood.
- Optimal protocols for FMT in HE require further investigation.
Purpose of the Study:
- To assess the safety and efficacy of FMT capsules in patients with prior overt HE.
- To compare the effects of five different FMT donors on HE outcomes.
- To identify microbial and clinical factors influencing FMT response in HE.
Main Methods:
- An open-label study involving FMT capsules administered five times over three weeks to ten patients with prior overt HE.
- Primary outcomes included changes in psychometric HE score (PHES) and serious adverse events (SAEs).
- Shallow shotgun metagenomic sequencing of stool samples was performed, with analysis using random forest and linear regression.
Main Results:
- FMT capsules significantly improved PHES scores after three doses, five doses, and four weeks post-treatment.
- No significant change was observed in Model for End-Stage Liver Disease (MELD) scores.
- Thirteen minor and three serious adverse events were reported; two SAEs were unrelated to FMT.
- Bifidobacterium adolescentis and B. angulatum were identified as predictors of improved PHES, with higher baseline levels of Bifidobacterium associated with better response.
Conclusions:
- FMT capsules are a safe and effective treatment for improving cognition in patients with HE.
- Donor and recipient characteristics significantly influence FMT efficacy.
- The abundance of specific Bifidobacterium species and short-chain fatty acid (SCFA) production may be key factors in successful FMT for HE.
