Gut bacteria drive liver damage when alcohol meets obesity, study finds
Researchers identified a causal link between gut microbiota and severe liver disease in people who drink alcohol and eat unhealthy diets. The finding suggests probiotics or targeted bacterial therapies could prevent progression to cirrhosis—opening a new treatment avenue for the millions with metabolic liver disease.
Originaltitel: Alcohol consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): understanding the gut–liver crosstalk for clinical translation
OBJECTIVE: In the present study, we investigated the role of the gut-liver crosstalk in the pathogenesis of steatotic liver disease (SLD) induced by the compounding and deleterious effects of alcohol and metabolic risk factors, and explored the potential translational aspects of microbiome-based interventions. DESIGN: The effects of combined exposure to alcohol and a high-fat, high-cholesterol diet (HFHC) Western diet (WD) were tested in a dietary mouse DUAL model and compared to mice fed only with WD. Liver and gut phenotypes were evaluated via histochemistry, flow cytometry, gene expression, proteomic, and metabolomic analyses. The effects on the gut microbiota were studied in both DUAL mice and MASLD patients with a history of alcohol consumption. Antibiotic-induced microbiota depletion (AIMD) and microbiota modulation therapies (probiotics and fecal microbiota transplant (FMT)) were performed in mice. Primary human hepatocytes and HepG2 cells were used to study the underlying mechanisms. Zebrafish larvae exposed to alcohol and a HFHC diet were used as a validation model. RESULTS: . AIMD improved pathology, indicating a causal role of the microbiota in the pathophysiology of DUAL steatohepatitis, whilst early microbiome modulation via FMT induced mild improvements in liver and gut physiology. CONCLUSIONS: These results indicated that the microbiota‒gut‒liver axis plays a crucial role in the progression of SLD intensified by alcohol and concurrent metabolic risk factors, thus providing a promising translational target for potential therapeutic interventions.