Dietary compounds regulate gene expression through n4- cytosine dna methylation in lactobacillus acidophilus

Abstract

Background and Aims The human gut microbiome is vital for maintaining overall health, with probiotics playing a pivotal role. While it is widely acknowledged that dietary compounds impact gene functionality within the gut microbiome, the precise mechanisms remain elusive. To shed light on this, we selected the commonly utilized probiotic bacterium, Lactobacillus acidophilus, as a model organism. Methods We accomplish this through a comprehensive multiomics approach, including PacBio sequencing, RNA sequencing, proteomics, and metabolomics analyses. Results We show here that dietary compounds, such as genistein and resveratrol, have the capacity to modify the epigenome of Lactobacillus acidophilus, thereby significantly influencing gene expression, primarily by altering N4-cytosine DNA methylation (m4C) in non-palindromic motifs. We detected unique changes in motifs for both genistein and resveratrol. These modifications potentially lead to notable changes in both gene expression and metabolite production. For example, we observed m4C modifications in motifs GACCCACCAAC and CAACTGGTCATG within the YSIRK-type signal peptide-containing protein-2 gene, which correlate with a remarkable 34-fold increase in gene expression in genistein-treated Lactobacillus acidophilus. This gene is associated with enhancing the binding of Lactobacillus species to mucus. We additionally tested these compounds on a different probiotic bacterium, Lacticaseibacillus paracasei, and noted comparable m4C alterations. Additionally, we examined the effects of other dietary compounds known to influence DNA methylation, such as caffeic acid, diallyl disulfide, and sodium butyrate, on Lactobacillus acidophilus gene expression.