Prevention of enteric bacterial infections and modulation of gut microbiota with conjugated linoleic acids producing <i>Lactobacillus</i> in mice

Abstract

Probiotics are recognized for outcompeting pathogenic bacteria by competitive receptor-mediated colonization and secretion of functional metabolites which are antimicrobial against certain microbes as well as improving host's gut health and immunity. Recently, we have constructed a bioactive <i>Lactobacillus casei</i> (LC) strain, LC^+<i>mcra</i> , by inserting <i>mcra</i> (myosin cross-reactive antigen) gene, which stimulates the conversion of conjugated linoleic acids. In this study, we evaluated the modulation of gut microbiome and protective roles of LC^+<i>mcra</i> against pathogenic <i>Salmonella enterica</i> serovar Typhimurium (ST) and enterohemorrhagic <i>E. coli</i> (EHEC) infections in BALB/cJ mice. We observed that LC^+<i>mcra</i> colonized efficiently in mice gut intestine and competitively reduced the infection with ST and EHEC in various locations of small and large intestine, specifically cecum, jejunum, and ileum (<i>p</i> < 0.05). Positive modulation of the cecal microbiota, for example, higher relative abundances of Firmicutes, lower relative abundances of Proteobacteria, and increased bacterial species diversity/richness, was detected in ST-challenged mice pretreated with LC^+<i>mcra</i> based on 16S metagenomic sequencing. Cytokine gene expression analysis indicated that mice pretreated with LC^+<i>mcra</i> associated with attenuated bacterial pathogen-induced gut inflammation. Furthermore, mice fed daily with LC^+<i>mcra</i> for one week could protect themselves from the impairments caused by enteric infections with ST or EHEC. These impairments include weight loss, negative hematological changes, intestinal histological alterations, and potential death. This <i>in vivo</i> study suggests that daily consumption of novel conjugated linoleic acids over-producing probiotic effectively improves intestinal microbiota composition and prevents/combats foodborne enteric bacterial infections with pathogenic <i>Salmonella</i> and diarrheagenic <i>E. coli</i>.