Preliminary insights into gut microbiome shifts as screening proxy for MASLD disease progression

Abstract Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a metabolic syndrome with chronic excessive non-alcohol related triglyceride accumulation in liver cells, is characterised by a gradient of hepatic inflammation and fibrosis which lead to hepatocellular carcinoma. Clinical diagnosis is commonly based on non-invasive imaging methods, but definitive and conclusive diagnostic is achieved throughout invasive liver biopsy. Recent research pointed to an association between unbalanced gut microbiome and MASLD pathogenesis. In this prospective pilot study we dissect the gradual disease phenotypes as per common clinical practices and gut microbiome profiling based on 16 S rRNA gene sequencing of stool samples from a set of 8 healthy and 46 MASLD-diagnosed individuals. Results evidenced gut microbiome shifts (both a reduction of microbial diversity and richness) as liver damage severity increases with respect to control subjects. Additionally, microbiome compositional data balancing revealed a slight discriminatory capacity between controls and patients’ groups or between patients groups, but with low power due to the reduced sample size. All in all, non-invasive proxies based on gut microbiome analyses might be useful as complementary tools for MASLD patients stratification and discrimination.