Fecal Microbial Transplant Capsules are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial.
Hepatology. 2019 Apr 30;:
Authors: Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, Fagan A, Hayward M, Holtz ML, Matherly S, Lee H, Osman M, Siddiqui MS, Fuchs M, Puri P, Sikaroodi M, Gillevet PM
Hepatic encephalopathy (HE) can cause major morbidity despite standard of care (SOC; rifaximin/lactulose). Fecal microbial transplant (FMT) enemas post-antibiotics are safe but the effect of FMT without antibiotics using the capsular route requires investigation.
AIM: To determine the safety, tolerability and impact on mucosal/stool microbiota and brain function in HE after capsular FMT in a randomized, single-blind, placebo-controlled clinical trial in Virginia.
METHODS: Cirrhotic patients with recurrent HE with MELD<17 on SOC were randomized 1:1 into receiving 15 FMT capsules vs placebo from a single donor enriched in Lachnospiraceae and Ruminococcaceae. Endoscopies with duodenal and sigmoid biopsies, stool analysis, cognition, serum lipopolysaccharide-binding protein (LBP) and duodenal anti-microbial peptide(AMP) expression at baseline. Clinical follow-up with SOC maintenance was performed till 5 months. FMT-assigned patients underwent repeat endoscopies 4-weeks post-enrollment.
RESULTS: 20 subjects on lactulose/rifaximin were randomized 1:1. MELD score was similar at baseline (9.6 vs 10.2) & study end (10.2 vs 10.5). 6 patients in the placebo group required hospitalizations compared to one in FMT, which was deemed unrelated to FMT. Infection/HE episodes were similar between groups. Baseline microbial diversity was similar in all tissues between groups. Post-FMT, duodenal mucosal diversity(p=0.01) increased with higher Ruminococcaceae, Bifidobacteriaceae and lower Streptococcaceae and Veillonellaceae. Reduction in Veillonellaceae were seen post-FMT in sigmoid(p=0.04) and stool(p=0.05). Duodenal E-cadherin (p=0.03) and Defensin A5 (p=0.03) increased while IL-6(p=0.02) and serum LBP(p=0.009) reduced post-FMT. EncephalApp performance improved post-FMT only(p=0.02).
CONCLUSION: In this phase 1 study, oral FMT capsules are safe and well-tolerated in patient with cirrhosis and recurrent HE. FMT was associated with improved duodenal mucosal diversity, dysbiosis and AMP expression, reduced LBP and improved EncephalApp performance. Further studies are needed to prove efficacy. This article is protected by copyright. All rights reserved.
PMID: 31038755 [PubMed - as supplied by publisher]