ALCOHOL-RELATED liver disease (ALD) is a leading cause of liver-related death worldwide, with liver fibrosis at the core of disease progression. A key driver of fibrosis is gut barrier dysfunction, which allows harmful substances to enter the portal circulation and trigger liver inflammation. Recent attention has turned to postbiotics, non-living microbial products, as a novel way to restore gut barrier integrity and potentially halt liver fibrogenesis.
A new randomised controlled trial, GALA-POSTBIO, investigated the efficacy of ReFerm®, an oat-based postbiotic fermented with Lactobacillus plantarum DSM 9843, in patients with advanced ALD. Over 24 weeks, 56 patients received either ReFerm® or a standard nutritional supplement (Fresubin®). The trial aimed to assess whether ReFerm® could reduce liver fibrosis, using the marker α-smooth muscle actin (α-SMA) in liver biopsies.
While the primary outcome, a ≥10% reduction in α-SMA, was reached in 29% of ReFerm® recipients versus 14% in the control group, the difference was not statistically significant. However, secondary outcomes were promising. Patients treated with ReFerm® showed improved markers of liver health, including reduced liver stiffness, lower levels of the fibrosis biomarker PRO-C3, and decreased circulating I-FABP, a marker of gut barrier damage.
Multi-omics analyses suggested that ReFerm® enhances gut barrier function and promotes hepatic regeneration without altering microbiome composition. Notably, improvements were linked to increased levels of neurotrophin-3 and SIRT2, both associated with liver repair.
Although ReFerm® contains both Lactobacillus plantarum and its metabolites, evidence from in vitro and clinical studies suggests the beneficial effects are driven by microbial components rather than live bacteria. This underscores the therapeutic potential of postbiotics, particularly for conditions like ALD where restoring the gut–liver axis is crucial.
While more research is needed, this study highlights ReFerm® as a safe and potentially effective approach to slowing fibrosis in patients with advanced ALD, by targeting the gut, rather than the liver directly.
Reference
Hansen JK et al. The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial. Nat Commun. 2025;16(1):5969.
