Intestinal epithelial cell-derived components regulate transcriptome of Lactobacillus rhamnosus GG

Abstract

Introduction: Intestinal epithelial cells (IECs) provide the frontline responses to the gut microbiota for maintaining intestinal homeostasis. Our previous work revealed that IEC-derived components promote the beneficial effects of a commensal and probiotic bacterium, Lactobacillus rhamnosus GG (LGG). This study aimed to elucidate the regulatory effects of IEC-derived components on LGG at the molecular level.

Methods: Differential gene expression in LGG cultured with IEC-derived components at the timepoint between the exponential and stationary phase was studied by RNA sequencing and functional analysis.

Results: The transcriptomic profile of LGG cultured with IEC-derived components was significantly different from that of control LGG, with 231 genes were significantly upregulated and 235 genes significantly down regulated (FDR <0.05). The Clusters of Orthologous Groups (COGs) and Gene Ontology (GO) analysis demonstrated that the predominant genes enriched by IEC-derived components are involved in nutrient acquisition, including transporters for amino acids, metals, and sugars, biosynthesis of amino acids, and in the biosynthesis of cell membrane and cell wall, including biosynthesis of fatty acid and lipoteichoic acid. In addition, genes associated with cell division and translation are upregulated by IEC-derived components. The outcome of the increased transcription of these genes is supported by the result that IEC-derived components significantly promoted LGG growth. The main repressed genes are associated with the metabolism of amino acids, purines, carbohydrates, glycerophospholipid, and transcription, which may reflect regulation of metabolic mechanisms in response to the availability of nutrients in bacteria.

Discussion: These results provide mechanistic insight into the interactions between the gut microbiota and the host.

Keywords: RNA sequencing; bacterial metabolism; bacterial transporter; commensal bacterium; intestinal epithelial cell; the microbial-host interaction; transcriptome.