Dietary Bioactive Compounds Trigger Distinct Epigenetic and Metabolic Reprogramming in Lactobacillus acidophilus

Lactobacillus acidophilus ATCC 4356 (LA), a key probiotic in the human gut microbiota, offers several health benefits. While dietary bioactive compounds are known to influence gut microbiota, their specific mechanisms remain unclear. This study investigated how certain dietary bioactive compounds impact LA gene expression and metabolism. Results showed each compound produces unique transcriptional, metabolic, proteomic, and epigenetic profiles in LA. Notably, dietary compounds altered the epigenetic landscape through N4-methylcytosine (4mC) modification, a relatively underexplored form of methyl modification that may play a role in regulating gene transcription. For instance, genistein treatment up-regulated 76 genes and the down-regulated 130 genes in LA. A gene involved in mucus-binding proteins, crucial for bacterial adhesion, was up-regulated 38-fold, likely due to 4mC modifications. Additionally, the gene coding for the melibiose operon regulatory protein increased 78-fold, enhancing melibiose (a prebiotic) production with genistein, but only 1.1-fold with sodium butyrate. This study highlights the potential of dietary compounds for microbial metabolic engineering, offering a non-GMO method for modulating bacterial performance and other biotechnology applications.