Fecal Microbiota Transplantation (FMT) & Hepatic encephalopathy (HE)

Why Use Fecal Microbiota Transplantation (FMT) for Hepatic encephalopathy (HE)

Fecal Microbiota Transplantation (FMT) is being studied for hepatic encephalopathy (HE) because the gut microbiome can contribute to the toxins and inflammation that affect the brain in cirrhosis. FMT aims to shift an imbalanced gut microbial community toward one that may produce fewer harmful compounds and support a healthier gut barrier. The hope is to reduce recurrent HE episodes, particularly for people who still have recurrences despite standard treatment with lactulose and rifaximin (1, 2).

Fecal Microbiota Transplantation (FMT) for Hepatic encephalopathy (HE): Reviews And Meta-Analyses

Three randomized trials (70 participants total) evaluated Fecal Microbiota Transplantation (FMT) plus standard care versus standard care alone for adults with cirrhosis and recurrent overt hepatic encephalopathy (HE) through September 2025. By 180 days, the frequentist meta-analysis suggested fewer Hepatic encephalopathy (HE) recurrences with FMT (RR 0.265, 95% CI 0.090–0.784), but the result was fragile: two of three sensitivity analyses lost statistical significance. The Bayesian analysis estimated a 97.3% probability of benefit, though its credible interval crossed no effect (RR 0.255, 95% CrI 0.057–1.039). Hospital readmission showed a non significant trend toward reduction, and no clear increase in serious harm was observed. Certainty was low for recurrence, readmission, and serious adverse events, and very low for mortality; small samples and wide prediction intervals leave substantial uncertainty. All trials came from one center and the same principal investigator, so larger independent multicenter trials are needed before drawing firm conclusions or defining optimal protocols (7).

A systematic review and meta-analysis of 21 randomized trials (1,746 participants) assessed probiotics, synbiotics, and Fecal Microbiota Transplantation (FMT) for hepatic encephalopathy. Compared with placebo or no treatment, microbiome therapies were associated with lower odds of minimal Hepatic encephalopathy (HE) (OR 0.41, 95% CI 0.19–0.90) and progression to overt Hepatic encephalopathy (HE) (OR 0.41, 95% CI 0.28–0.61). They were also associated with fewer serious adverse events (OR 0.14, 95% CI 0.04–0.47) and hospitalizations (OR 0.38, 95% CI 0.19–0.79). Pooled results indicated lower ammonia levels (WMD −9.26, 95% CI −16.92 to −1.61). The abstract also reports lower NCT scores, but its estimate and confidence interval appear inconsistent and should be checked against the full article before reuse. These pooled findings span heterogeneous interventions and trials, so they do not show that each therapy works equally well or establish which is superior (8).

The review assessed fecal microbiota transplantation (FMT) as a potential treatment for hepatic encephalopathy (HE), a cognitive complication of chronic liver disease. Searches of PubMed and EMBASE, conducted on February 8, 2021, identified eight eligible studies: two randomized trials, three case reports, and three rodent studies, involving 39 patients and 39 rodents. Neurocognitive test results improved in four human studies and two rodent studies; donor-origin microbes were detected in some recipients a year after FMT. The review also reported fewer readmissions after FMT than with standard care. Proposed mechanisms include reducing gut ammonia production and absorption, and improving ammonia clearance through better liver function. Because the studies were small and follow-up was limited, larger randomized trials are needed; these findings do not establish FMT as standard HE treatment (6).

Fecal Microbiota Transplantation (FMT) for Hepatic encephalopathy (HE): Randomized clinical trials (RCTs)

The randomized clinical phase II treatment trial, identified as NCT03420482 - Fecal Microbiota Transplant (FMT) & Hepatic encephalopathy (HE), demonstrated that FMT capsules improved cognitive function in individuals with HE. The effects varied depending on the characteristics of both the donor and the recipient (5).

The randomized, placebo-controlled phase I trial XXX - Fecal Microbiota Transplantation (FMT) & Hepatic Encephalopathy (HE) demonstrated that oral FMT capsules are safe and well-tolerated in patients with cirrhosis and recurrent hepatic encephalopathy. The use of FMT was associated with increased diversity in the duodenal mucosa, correction of dysbiosis, and heightened expression of antimicrobial peptides (AMPs). Furthermore, there was a decrease in lipopolysaccharide-binding protein (LBP) levels and an enhancement in EncephalApp performance. Nonetheless, additional research is required to validate the efficacy of these findings (4)

The randomized clinical phase trial, identified as NCT02636647 - Fecal Microbiota Transplantation (FMT) vs SoC & Hepatic encephalopathy (HE), demonstrated that fecal microbiota transplantation (FMT) from a carefully chosen donor led to a reduction in hospitalizations, enhanced cognitive function, and improved dysbiosis in patients with cirrhosis experiencing recurrent hepatic encephalopathy (HE) (3).

For the clinical phase I/II treatment trial NCT02255617 - Fecal Microbiota Transplantation (FMT) & Hepatic encephalopathy (HE), a full manuscript with detailed efficacy/safety data does not yet appear in PubMed‑indexed form as of January 2026

Fecal Microbiota Transplantation (FMT) for Hepatic encephalopathy (HE): Conclusion

Fecal Microbiota Transplantation (FMT) shows promise as an add-on to standard care for recurrent hepatic encephalopathy: small trials suggest it may reduce recurrences and hospitalizations and improve cognitive function and gut-microbiome measures. However, the evidence remains uncertain because studies are small, results are not consistently robust, and the trials have limited independent replication. FMT should therefore not yet be considered established treatment; larger, independent multicenter trials are needed to confirm its benefits, safety, and best protocols.

References:

(1) Hassouneh & Bajaj 2021 J Clin Med 10(2): 330
(2) Shah et al. 2024 World J Hepatol 16(1): 17-32
(3) Bajaj et al. 2017 Hepatology 66:1727–38
(4) Bajaj et al. 2019 Hepatology 70(5): 1690-1703
(5) Bloom et al. 2022 Hepatol Commun 6(8): 2079-2089
(6) Madsen et al. 2021 Scand J Gastroenterol 256(5): 560-569
(7) Das et al. 2026 Eur J Med Res doi.org/10.1186/s40001-026-05286-9
(8) Gao et al. 2023 Eur J Gastroenterol Hepatol 35(9): 927-937

see also:
Fecal Microbiota Transplantation (FMT) & Liver Fibrosis / Cirrhosis
Hepatic Encephalopathy (HE) & Drugs/Treatments
Microbiome-based therapeutics & Hepatic Encephalopathy (HE)
RBX2660 & Hepatic encephalopathy (HE)
RBX7455 & Hepatic encephalopathy (HE)