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

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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], <i>p</i> = 0.001) and in several quality-of-life domains, including abdominal symptoms, fatigue, systemic manifestations, activity and emotional function (<i>p</i> < 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. <b>Conclusions</b>: 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.