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

Abstract

Probiotics are recognized for outcompeting pathogenic bacteria by competitive receptormediated 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 Lactobacillus casei (LC) strain, LC +mcra , by inserting mcra (myosin crossreactive 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 +mcra against pathogenic Salmonella enterica serovar Typhimurium (ST) and enterohemorrhagic E. coli (EHEC) infections in BALB/cJ mice. We observed that LC +mcra 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 (p < 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 +mcra based on 16S metagenomic sequencing. Cytokine gene expression analysis indicated that mice pretreated with LC +mcra associated with attenuated bacterial pathogen-induced gut inflammation. Furthermore, mice fed daily with LC +mcra 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 in vivo 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 Salmonella and diarrheagenic E. coli.

Preventive Antibiotic Treatment Increases Neonatal Chicks Susceptibility to Salmonella Infection Via Disrupting Gut Microbiota and Linoleic Acid Metabolism

“…And we believe that CLA reduces the Salmonella intestinal colonization including several aspects. Firstly, CLA treatments could signi cantly upregulated the concentration of tight junction proteins (ZO-1, occludin, E-cadherin 1 and claudin-3) and ameliorated epithelial apoptosis [96][97][98], which protect intestinal from the impairments caused by Salmonella infection. Secondly, CLA can modulate the gut in ammation including attenuated the expression of proin ammatory cytokines (TNF-α, INF-γ, IL-1β, and IL-6 and IL-17) while upregulating the level of the anti-in ammatory cytokine IL-10 [96][97][98][99][100][101].…”

Preventive&nbsp;Antibiotic&nbsp;Treatment&nbsp;Increases&nbsp;Susceptibility&nbsp;of&nbsp;Neonatal&nbsp;chicks&nbsp;to&nbsp;Salmonella&nbsp;Infection&nbsp;via&nbsp;Disrupting&nbsp;Gut&nbsp;Microbiota&nbsp;and&nbsp;Linoleic&nbsp;Acid&nbsp;Metabolis

“…We suggest that CLA reduces intestinal colonization by Salmonella by in uencing several processes. Firstly, CLA treatment considerably upregulated the concentration of tight junction proteins (ZO-1, occludin, E-cadherin 1 and claudin-3) and ameliorated epithelial apoptosis [96][97][98], which protects intestinal cells from the impairment caused by Salmonella infection. Secondly, CLA modulates gut in ammation by attenuating the expression of proin ammatory cytokines (TNF-α, INF-γ, IL-1β, and IL-Lactobacillus competitively excludes Salmonella in a mixed-culture condition [102].…”

“…and and upregulating the level of anti-in ammatory cytokine IL-10[96][97][98][99][100][101]. Thus, CLA exhibits anti-in ammatory effects that reduce gut colonization by Salmonella.…”

Competitive reduction of poultry-borne enteric bacterial pathogens in chicken gut with bioactive Lactobacillus casei

“…The amount and types of bioactive metabolites produced by beneficial microbes are vastly influenced by undigested dietary components and/or prebiotics 11,13 . Any potential prebiotic intended for use has to comply with some regulations, like possessing the "Generally Recognized as Safe (GRAS)" status, being assessed for appropriate dose and potential side effects, must be free of contaminants and impurities and must not cause alterations to the intestinal microbiota that could negatively affect the host 18 .…”

“…Considering this, our research team over-expressed the myosin-cross-reactive antigen (Mcra) ('mcra' gene obtained from L. rhamnosus, another probiotic strain) 33 for linoleate isomerase over-production in Lactobacillus casei (LC). The mcra over-expressing probiotic, named as "LC +mcra ", showed enhanced activities, including anti-inflammatory and antimicrobial effects both in vitro and in vivo animal model (mice) 13,31 . It has also been reported that LC +mcra induced no detrimental effect on mice gut, rather it improved the murine gut health through the modulation gut microbiome 13 .…”