# Clinical and MicroRNA Responses to Fecal Microbiota Transplantation in Patients with Alcohol-Related Cirrhosis: A Pilot Study

## TL;DR

This pilot study explores how fecal microbiota transplantation affects clinical outcomes and microRNA levels in patients with alcohol-related cirrhosis.

## Contribution

The study is the first to explore the relationship between fecal microbiota transplantation and microRNA expression in patients with advanced liver disease.

## Key findings

- FMT was well tolerated with no severe adverse events.
- Improvements were observed in clinical scores and quality-of-life domains.
- miR-125 and miR-146 were associated with clinical status and hepatic encephalopathy severity.

## Abstract

Background/Objectives: Alcohol-related liver cirrhosis is a systemic disorder characterized by profound immune, metabolic and gut–liver axis dysregulation. Emerging evidence highlights a bidirectional interaction between the intestinal microbiota and host microRNAs (miRNAs), positioning this axis as a potential regulator of systemic homeostasis. However, human data exploring the impact of microbiota modulation on miRNA expression in advanced liver disease remain limited. Methods: Six patients with alcohol-induced liver cirrhosis underwent fecal microbiota transplantation (FMT). Safety was assessed through clinical and paraclinical monitoring at predefined intervals. Quality of life was evaluated pre- and post-intervention using a validated liver-specific questionnaire. Fecal expression of miR-21-5p, miR-122-5p, miR-125-5p, miR-146-5p and miR-155-5p was analyzed and correlations with clinical domains, demographic variables and hepatic encephalopathy severity were explored. Results: FMT was well tolerated, with no severe adverse events reported. Preliminary improvements were observed in total clinical score (3.22 [3.06–3.57] vs. 4.25 [4.20–4.26], p = 0.001) and in several quality-of-life domains, including abdominal symptoms, fatigue, systemic manifestations, activity and emotional function (p < 0.05), while worry/concern scores remained unchanged. miR-125 and miR-146 demonstrated consistent associations with clinical status both before and after FMT, whereas miR-21 correlated mainly with age and body mass index. Notably, miR-125 and miR-146 were also associated with post-FMT hepatic encephalopathy severity, supporting their potential value as molecular correlates of clinical response in this exploratory study. Conclusions: In this pilot study, FMT appeared safe and was temporally associated with improvements in clinical parameters in alcohol-related cirrhosis, alongside dynamic changes in fecal miRNA expression. These preliminary findings support a potential microbiota–miRNA interaction and warrant validation in larger, controlled longitudinal studies.