Probiotic lactobacilli mediate their immunoregulatory functions in intestinal cells via modulation of H3 histone acetylation.

Abstract

Probiotics maintain intestinal homeostasis through the regulation of the immune response of the host. Hence, the role of histone modifications as epigenetic agents on immune modulations by potential probiotic bacteria has been investigated. Human colonic epithelial cells (Caco-2) pre-treated with class I histone deacetylase (HDAC) specific inhibitor, MS-275, were incubated either with potential probiotic bacteria (Limosilactobacillus fermentum MTCC 5898 and Lacticaseibacillus rhamnosus MTCC 5897) or Escherichia coli (ATCC 14948) as an inflammatory agent. Initially, transcriptional expression of potential immune related genes (IL-6, IL-8 and hBD-2) was analyzed using RT-qPCR and later H3 histone acetylation (H3Ac) at the promoter region of these genes was confirmed with chromatin immunoprecipitation (ChIP) assay respectively. Potentially probiotic L. fermentum (MTCC 5898) significantly suppressed (P<0.05) the inhibitor-mediated elevated expression of immune related genes while another strain L. rhamnosus (MTCC 5897) did not influence these gene expression results. In contrast, as an inflammatory agent, E. coli (ATCC 14948) synergistically augmented the expression of immune related genes. Later, ChIP analysis confirmed the occurrence of H3 acetylation at these genes' promoter region, which was directly related to the transcriptional activity of host epithelial cells stimulated by L. fermentum and E. coli respectively. But in the case of L. rhamnosus, MTCC 5897, acetylation did not follow the transcription pattern and potentiated H3Ac on the promoter regions of these genes. Potential probiotics used in the study were found to regulate the immune response of host cells through histone acetylation in a strain-specific manner.