Effects of Probiotics (P. Pentosaceus, L. Lactis or L. Helveticus) in Patients With Nonalcoholic Hepatitis

Metabolic dysfunction-associated fatty liver disease applies to adults exhibiting hepatic steatosis identified through imaging techniques, blood biomarkers, or liver histology. This diagnosis is made in individuals who are overweight or obese, or who have type 2 diabetes mellitus, or at least two other metabolic risk abnormalities. Subsequently, in June 2023, a multi-society Delphi consensus statement was issued on a revised nomenclature for fatty liver diseases. This statement introduced the term metabolic dysfunction-associated steatotic liver disease (MASLD), effectively replacing the previous nonalcoholic fatty liver disease. Representative etiologies of MASLD are known to include insulin resistance, lipid toxicity due to excessive fat accumulation, inflammatory response, and endoplasmic reticulum stress.

The global rise in obesity has contributed to the increased prevalence of MASLD. MASLD affects approximately 30% of the global adult population, with its prevalence rising from 22% to 37% between 1991 and 2019. This increase aligns with the growing rates of obesity and related conditions worldwide. The more severe manifestation of MASLD, known as metabolic dysfunction-associated steatohepatitis (MASH), is histologically characterized by lobular inflammation and hepatocyte ballooning and is linked to a higher risk of fibrosis progression. Among individuals diagnosed with MASLD who do not meet criteria for a liver biopsy, the prevalence of MASH is approximately 7%. MASLD is one of the most common causes of chronic liver disease and liver-related death and serves as a risk factor for extrahepatic diseases such as diabetes and cardiovascular disease. As a result, the burden of social and economic costs caused by the disease is increasing.

Recently, interest in the role of the gut microbiome in the pathogenesis and treatment of liver diseases has increased, and the disease linkage caused by intestinal bacterial imbalance has been identified [16, 17]. Animal studies have demonstrated potential causal roles of the gut microbiota in MASLD [18, 19]. Human studies have described microbiome alterations in healthy individuals and patients with MASLD and have found several consistent specific taxa that differentiate between healthy individuals and patients with MASLD and advanced liver disease. Despite unknown mechanisms and lack of validation, therapeutic strategies utilizing the gut microbiome have the potential to provide beneficial effects in patients with MASLD.

Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. In our previous animal studies, Lactobacillus and Pediococcus supplementation improved MASLD by modulating gut microbiota and inflammation. Additional experiments with candidate strains have shown promising results in the prevention of MASLD progression. Several randomized controlled trials using ultrasonography and MASLD diagnostic markers of short duration have suggested that administration of probiotics may have a positive effect on hepatic steatosis and insulin resistance in patients. However, none of the previous studies reported the therapeutic effect of probiotics on the microbiome in patients with MASLD. In this clinical trial, we aimed to investigate whether administering probiotics for 8 weeks could effectively improve blood biochemical parameters and induce alterations in the gut microbiota among patients diagnosed with MASLD.