FMT restores gut barrier function, improves severe alcohol associated hepatitis outcomes

Improvements in intrahepatic and circulatory inflammation markers were observed after fecal microbiota transplantation in patients with severe alcohol associated hepatitis, according to a presenter at The Liver Meeting Digital Experience.

“The gut permeability was reversed, which suggests the effectiveness of cellular remodeling and reasons for a better survival after FMT,” Sukriti Baweja, PhD, assistant professor of molecular and cellular medicine at the Institute of Liver and Biliary Sciences, said during the presentation. “Our study provides evidence that improvement in severe alcoholic hepatitis patients post-FMT by day 28, [mucosal associated invariant T cells] cells may aid in antimicrobial activity in circulation and increase the overall mortality.”

Baweja and colleagues identified 27 patients (100% men; mean age, 46 years) with severe alcohol hepatitis who underwent FMT and were analyzed pre- and post-FMT. They also included 20 healthy controls. Flow cytometry was used to perform high-dimensional immune profiling for monocytes, neutrophils, T helper type 1, T helper type 2, T helper type 17, mucosal associated invariant T cells (MAITs), T-regulatory and B-cell subsets and intracellular cytokines in peripheral blood. Intrahepatic MAITs were studied via liver biopsy.

Investigators used q-Real time PCR to assess genes correlated with inflammation, mucosal immunity and permeability. Microvesicles were used to analyze cellular injury.

Compared with baseline, the T-cell subsets post-FMT in systemic circulation were significantly altered. The frequency increased for CD3⁺CD8⁺ (P = .026), CD3⁺CD4^-CD8⁺ MAITs (CD161⁺TCR Valpha7.2⁺; P = .0) and Th17 (CD3⁺CD4⁺RoRg⁺), whereas CD3^-CD19⁺ frequency declined (P = .044).

Baweja and colleagues noted post-FMT, the IL-17A and IFN-producing MAITs (both, P = .0) were significantly reduced. Results showed activation markers CD25 ⁺ (P = .0) and CD69 ⁺ were low on MAITs. At day 28, the intrahepatic MAITs were decreased after FMT (P = .032).

“The intestinal barrier improved as the expression of tight junctions ZO1(P = .0) and Claudin1 (P = .0) were increased,” Baweja and colleagues wrote in the abstract. “Intestinal epithelial cells associated [microvesicles] were significantly decreased (P = .004) in circulation.”

According to Baweja, post-FMT, genes correlated with permeability and inflammation were also reduced (P < .05).