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

Gut Microbes. 2020 May 3;11(3):433-452. doi: 10.1080/19490976.2019.1638724. Epub 2019 Aug 14.

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 Lactobacillus casei (LC) strain, LC+mcra , by inserting mcra (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+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.

Keywords: Probiotic; conjugated linoleic acid; enteric bacterial pathogen; intestinal microbiota; metagenomics; salmonellosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cecum / microbiology
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA, Bacterial / genetics
  • Enterohemorrhagic Escherichia coli / growth & development
  • Escherichia coli Infections / pathology
  • Escherichia coli Infections / prevention & control*
  • Female
  • Gastrointestinal Microbiome*
  • Ileum / microbiology
  • Inflammation / genetics
  • Inflammation / microbiology
  • Jejunum / microbiology
  • Lacticaseibacillus casei / physiology*
  • Linoleic Acids, Conjugated / metabolism
  • Linoleic Acids, Conjugated / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Probiotics / pharmacology
  • RNA, Ribosomal, 16S / genetics
  • Salmonella Infections / pathology
  • Salmonella Infections / prevention & control*
  • Salmonella typhimurium / growth & development

Substances

  • Cytokines
  • DNA, Bacterial
  • Linoleic Acids, Conjugated
  • RNA, Ribosomal, 16S

Grants and funding

This study was funded by Tier-1 (2945060) grants awarded to Debabrata Biswas.