Abstract
BackgroundThe incidence of human Campylobacter jejuni infections is progressively increasing worldwide. Probiotic compounds might open up valuable tools to decrease pathogen burden and subsequent pro-inflammatory immune responses, but in vivo data are scarce.Methods and resultsSecondary abiotic mice generated by broad-spectrum antibiotic treatment were perorally challenged with the commercial probiotic compound VSL#3 consisting of Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus delbrueckii ssp. bulgaricus) either 5 days before (i.e. prophylactic regimen) or after (i.e. therapeutic regimen) peroral C. jejuni strain 81–176 infection, and analyzed 3 weeks following the initial bacterial re-association. Upon challenge, mice were colonized with the probiotic bacteria and/or C. jejuni at comparable intestinal loads, but co-colonization did not result in reduction of the pathogen burden. Remarkably, prophylactic as well as therapeutic VSL#3 treatment of C. jejuni infected mice ameliorated intestinal apoptosis and pro-inflammatory immune responses as indicated by lower numbers of innate and adaptive immune cell populations in the murine colon upon probiotic prophylaxis or treatment and reduced colonic concentrations of pro-inflammatory mediators including IL-6 and MCP-1. Importantly, concentrations of anti-inflammatory mediators such as IL-10 were significantly elevated in the colon of probiotics treated mice as compared to untreated controls. Strikingly, prophylactic VSL#3 treatment attenuated C. jejuni induced systemic pro-inflammatory responses as indicated by less TNF and IL-12p70 secretion in the spleen of VSL#3 pre-treated as compared to non-treated mice.ConclusionAdministration of probiotic formulations such as VSL#3 might open up valuable strategies for prophylaxis and/or treatment of C. jejuni induced intestinal and systemic sequelae in vivo by the suppression of pro-inflammatory and induction of anti-inflammatory responses.
Highlights
The incidence of human Campylobacter jejuni infections is progressively increasing worldwide
Administration of probiotic formulations such as VSL#3 might open up valuable strategies for prophylaxis and/or treatment of C. jejuni induced intestinal and systemic sequelae in vivo by the suppression of pro-inflammatory and induction of anti-inflammatory responses
Intestinal colonization densities in secondary abiotic mice following peroral re‐colonization with probiotic bacteria and/or C. jejuni strain 81–176 infection In the present study we investigated the potential of probiotic bacteria in the commercial formulation VSL#3 to reduce pathogen burdens and to ameliorate pro-inflammatory immune responses upon C. jejuni infection in vivo
Summary
The incidence of human Campylobacter jejuni infections is progressively increasing worldwide. Colonized mice, for instance, are protected from C. jejuni infection due to the host specific microbiota composition exerting physiological colonization resistance [3, 12]. Upon virtual eradication of the intestinal microbiota by broad-spectrum antibiotic treatment secondary abiotic mice became highly susceptible to C. jejuni colonization and exhibited key features of human campylobacteriosis such as apoptosis and inflammation in the colon [12]. Colonization resistance was restored in secondary abiotic mice recolonized with a murine microbiota. Both secondary abiotic mice and secondary abiotic animals re-colonized with a murine microbiota are well suited to unravel the triangular relationship between intestinal pathogens, bacteria and the host immune system in vivo [12, 14]
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