Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Junshin Clinic Bile Acid Institute, Tokyo, Japan.
OpenBiome, Somerville, Massachusetts, USA.
George Mason University, Manassas, Virginia, USA.
Cirrhotic patients are often exposed to antibiotics that can lead to resistance and fungal overgrowth. The role of fecal microbial transplant (FMT) to restore gut microbial function is unclear in cirrhosis. In an FDA-monitored Phase 1 clinical safety trial, decompensated cirrhotic patients on standard therapies (lactulose and rifaximin) were randomized to standard-of-care (SOC, no antibiotics/FMT) or 5 days of broad-spectrum antibiotics followed by FMT from a donor enriched in Lachnospiraceae and Ruminococcaceae. Microbial composition (diversity, family-level relative abundances), function [fecal bile acids (BA) deconjugation, 7α-dehydoxylation, short-chain fatty acids (SCFA)] and correlations between Lachnospiraceae, Ruminococcaceae and clinical variables were analyzed at baseline, post-antibiotics and 15 days post-FMT. FMT was well-tolerated. Post-antibiotics, there was a reduced microbial diversity and autochthonous taxa relative abundance. This was associated with an altered fecal SCFA and BA profile. Correlation linkages changes from beneficial at baseline to negative after antibiotics. All these parameters became statistically similar post-FMT to baseline levels. No changes were seen in the SOC group.
In patients with advanced cirrhosis on lactulose and rifaximin, FMT restored antibiotic-associated disruption in microbial diversity and function.