Abstract
Lactobacillus fermentum is found in fermented foods and thought to be harmless. In vivo and clinical studies indicate that some L. fermentum strains have beneficial properties, particularly for gastrointestinal health. However, L. fermentum AGR1487 decreases trans-epithelial electrical resistance (TEER), a measure of intestinal barrier integrity. The hypothesis was that L. fermentum AGR1487 decreases the expression of intestinal cell tight junction genes and proteins, thereby reducing barrier integrity. Transcriptomic and proteomic analyses of Caco-2 cells (model of human intestinal epithelial cells) treated with L. fermentum AGR1487 were used to obtain a global view of the effect of the bacterium on intestinal epithelial cells. Specific functional characteristics by which L. fermentum AGR1487 reduces intestinal barrier integrity were examined using confocal microscopy, cell cycle progression and adherence bioassays. The effects of TEER-enhancing L. fermentum AGR1485 were investigated for comparison. L. fermentum AGR1487 did not alter the expression of Caco-2 cell tight junction genes (compared to L. fermentum AGR1485) and tight junction proteins were not able to be detected. However, L. fermentum AGR1487 increased the expression levels of seven tubulin genes and the abundance of three microtubule-associated proteins, which have been linked to tight junction disassembly. Additionally, Caco-2 cells treated with L. fermentum AGR1487 did not have defined and uniform borders of zona occludens 2 around each cell, unlike control or AGR1485 treated cells. L. fermentum AGR1487 cells were required for the negative effect on barrier integrity (bacterial supernatant did not cause a decrease in TEER), suggesting that a physical interaction may be necessary. Increased adherence of L. fermentum AGR1487 to Caco-2 cells (compared to L. fermentum AGR1485) was likely to facilitate this cell-to-cell interaction. These findings illustrate that bacterial strains of the same species can cause contrasting host responses and suggest that food-safe status should be given to individual strains not species.
Highlights
It is thought that symbiotic bacteria of the human gastrointestinal tract may be harmful under certain conditions [1]
The effect of L. fermentum AGR1485 was inconsistent; it had a positive effect on trans-epithelial electrical resistance (TEER) compared to control media in some assays (Figures 1a and 1e); in the other assays L. fermentum AGR1485 did not cause a change in TEER compared to control media (Figures 1b and 1c)
Genes that were differentially expressed in Caco-2 cells treated with L. fermentum AGR1487 compared to L. fermentum AGR1485 were significantly over-represented in a number of KEGG pathways, the top 5 of which were Pathogenic Escherichia coli infection, Gap junction, Glycosaminoglycan biosynthesis - chondroitin sulphate, mitogenactivated protein kinase (MAPK) signaling pathway and Phagosome (Table 1)
Summary
It is thought that symbiotic bacteria of the human gastrointestinal tract may be harmful under certain conditions [1]. The term ‘pathobionts’ is used to describe microbes with pathogenic potential associated with chronic inflammatory conditions linked to environmental and/or genetic alterations [2]. Pathobionts differ from opportunistic pathogens (which often cause acute infections and are typically acquired from the environment) because they are harmless to a healthy host. Lactobacillus fermentum is commonly found in fermented food products and is considered a ‘‘generally recognised as safe’’ (GRAS) organism by the US Food and Drug Administration (FDA). In vivo studies indicate that some L. fermentum strains have beneficial properties, in relation to gastrointestinal health. L. fermentum BR11 reduces colitis in rats [3–
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