The Intestinal Microbiota Influences Campylobacter jejuni Colonization and Extraintestinal Dissemination in Mice

Abstract

e Campylobacter jejuni is a leading cause of human foodborne gastroenteritis worldwide. The interactions between this pathogen and the intestinal microbiome within a host are of interest as endogenous intestinal microbiota mediates a form of resistance to the pathogen. This resistance, termed colonization resistance, is the ability of commensal microbiota to prevent colonization by exogenous pathogens or opportunistic commensals. Although mice normally demonstrate colonization resistance to C. jejuni, we found that mice treated with ampicillin are colonized by C. jejuni, with recovery of Campylobacter from the colon, mesenteric lymph nodes, and spleen. Furthermore, there was a significant reduction in recovery of C. jejuni from ampicillin-treated mice inoculated with a C. jejuni virulence mutant (⌬flgL strain) compared to recovery of mice inoculated with the C. jejuni wildtype strain or the C. jejuni complemented isolate (⌬flgL/flgL). Comparative analysis of the microbiota from nontreated and ampicillin-treated CBA/J mice led to the identification of a lactic acid-fermenting isolate of Enterococcus faecalis that prevented C. jejuni growth in vitro and limited C. jejuni colonization of mice. Next-generation sequencing of DNA from fecal pellets that were collected from ampicillin-treated CBA/J mice revealed a significant decrease in diversity of operational taxonomic units (OTUs) compared to that in control (nontreated) mice. Taken together, we have demonstrated that treatment of mice with ampicillin alters the intestinal microbiota and permits C. jejuni colonization. These findings provide valuable insights for researchers using mice to investigate C. jejuni colonization factors, virulence determinants, or the mechanistic basis of probiotics.

A Glance at Prokaryotes and Eukaryotes Interplay and Campylobacter jejuni–Host Interaction

“…Mice devoid of intestinal microbiota (germfree) and mice with a defined microbiota (gnotobiotic) have been shown to be more susceptible to C. jejuni colonization than mice with normal intestinal microbiota. For example, C. jejuni effectively colonizes germfree mice and disseminates to immune tissues, including the mesenteric lymph nodes (MLN) (Lee et al 1986;Youssef et al 1987;Jesudason et al 1989;O'Loughlin et al 2015). However, germfree mice demonstrate altered lymphoid development, resulting in an impaired immune response (Szeri et al 1976;Savidge et al 1991;Shroff and Cebra 1995;O'Loughlin et al 2015).…”

“…For example, C. jejuni effectively colonizes germfree mice and disseminates to immune tissues, including the mesenteric lymph nodes (MLN) (Lee et al 1986;Youssef et al 1987;Jesudason et al 1989;O'Loughlin et al 2015). However, germfree mice demonstrate altered lymphoid development, resulting in an impaired immune response (Szeri et al 1976;Savidge et al 1991;Shroff and Cebra 1995;O'Loughlin et al 2015). There are documented instances that mice are susceptible to colonization with C. jejuni (Blaser et al 1983;Chang and Miller 2006;O'Loughlin et al 2015).…”

“…Collectively, the intestinal commensal microbiota provides the host with numerous physiological benefits, including vitamin synthesis, tissue integrity, digestion, fermentation of proteins and polysaccharides, bile salt metabolism, and stimulation of the immune system (Blaut and Clavel 2007;O'Loughlin et al 2015). One additional physiological benefit of the intestinal microbiota is the enhancement of host immune defenses by inhibiting growth of potentially pathogenic microorganisms (colonization resistance).…”

“…The intestinal microbiota of healthy mammals is typically dominated by organisms from the phyla Firmicutes (Gram-positive bacteria) and Bacteroidetes (Gram-negative bacteria) (Holmes et al 2011;O'Loughlin et al 2015). Collectively, the intestinal commensal microbiota provides the host with numerous physiological benefits, including vitamin synthesis, tissue integrity, digestion, fermentation of proteins and polysaccharides, bile salt metabolism, and stimulation of the immune system (Blaut and Clavel 2007;O'Loughlin et al 2015).…”

“…One additional physiological benefit of the intestinal microbiota is the enhancement of host immune defenses by inhibiting growth of potentially pathogenic microorganisms (colonization resistance). Colonization resistance prevents pathogens from establishing a niche and inhibits the outgrowth of opportunistic pathogens (Lawley and Walker 2013;O'Loughlin et al 2015).…”