Elucidating the mechanism of a Novel Synbiotic formulation in Non alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic condition that affects one in every four individuals globally. Its etiology is directly linked to oxidative stress, insulin resistance, and type 2 diabetes mellitus (T2DM), which can lead to life-threatening conditions such as non-alcoholic steatohepatitis (NASH), cirrhosis, and liver failure. Given the multifaceted nature of NAFLD and no approved medications, a holistic approach is necessary to address its pathophysiological consequences. In this regard, probiotics such as Lactobacillus have demonstrated numerous health benefits, while prebiotics that promote the growth and survival of probiotic microorganisms, are known for their system-wide advantages. Additionally, wild edible plants are a rich source of oligosaccharides with additional benefits of antioxidant phytochemicals and other compounds. Against this backdrop, this study sought to develop and optimize a new synbiotic formulation by isolating prebiotics from wild edible plants and characterizing their properties. The synbiotic formulations using Lactobacillus cultures and isolated prebiotics were prepared, further evaluated for in vitro studies including antioxidant potential and cell-based assays using HT-29 adenocarcinoma cell line. The synbiotic formulation (Lactobacillus plantarum and Emblica officinalis) demonstrated the highest potential in cell-based assays such as microbial adhesion and HT-29 cell viability and exhibited considerable antioxidant activity. Fatty acid analysis by GC-FID was also performed and it was found that E. officinalis modulated the fatty acid composition of L. plantarum in synbiotic formulation, producing uncommon fatty acids. In molecular docking analysis, these uncommon fatty acids were effective at binding with the G-protein coupled receptor (GPR40), which might trigger glucagon-like peptide-1 (GLP-1) secretion.