Beneficial changes in microbial composition and functionality with capsular fecal microbiota transplant lead to improved cognition in patients with cirrhosis and recurrent hepatic encephalopathy, according to study data presented at The American Association for the Study of Liver Diseases’ The Liver Meeting 2019, held November 8 to 12 in Boston, Massachusetts.

In order to determine how changes in microbiota after fecal microbiota transplant correlate with changes in fecal bile acid moieties, inflammation, and cognition, researchers analyzed data from 20 patients with cirrhosis and recurrent hepatic encephalopathy who were receiving lactulose/rifaximin. These patients were randomly assigned in a 1:1 ratio to receive either 15 fecal microbiota transplant capsules or placebo. Fecal microbiota transplant was conducted via a single donor enriched in Lachnospiraceae/Ruminococcaceae, which are associated with secondary bile acid generation and subsequent functional consequences.

Researchers collected stool and blood samples and analyzed cognition (using EncephalApp) at baseline and 30 days post-intervention. Stool microbiota was analyzed using 16S ribosomal RNA & bile acids using liquid chromatography-electrospray tandem mass spectrometry. Fecal bile acid moieties analyzed were total, primary, secondary, deconjugated, and tertiary bile acids. Secondary/primary bile acid ratios were calculated. Serum was also analyzed for lipopolysaccharide‐binding protein (LBP) and interleukin 6 (IL‐6).

At follow-up, EncephalApp total score improved in patients who received fecal microbiota transplant (P <.05). There was a significant engraftment of donor microbiota with higher Ruminococcaceae and Lachnospiraceae in stool duodenum in patients who received fecal microbiota transplant. A significant increase in secondary/primary bile acid ratio in those who received fecal microbiota transplant was observed, whereas reductions in LBP and IL-6 were seen only in the fecal microbiota transplant group.

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Correlation networks created between bile acids, microbiota, LBP, IL‐6, and cognition showed higher complexity after fecal microbiota transplant vs placebo. At study end, beneficial bacteria (Ruminococcaceae and Verrucomicrobiaceae) became significantly positively correlated with each other and negatively with inflammation, and were associated with better EncephalApp scores post‐fecal microbiota transplant vs placebo.

Cognitive improvement was “associated with beneficial changes in microbial composition and functionality with greater secondary [bile acid] formation, and differential correlations with bacterial translocation and inflammation,” concluded the researchers.

Disclosure: Jasmohan S. Bajaj declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of his disclosures.

Reference

Bajaj JS, Salzman N, Kakiyama G, et al. Cognitive improvement with capsular fecal microbial transplant in hepatic encephalopathy is associated with changes in microbial function and inflammation. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Poster 229.