Amelioration of intestinal and systemic sequelae of murine Campylobacter jejuni infection by probiotic VSL#3 treatment

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.

The conundrum of colonization resistance against Campylobacter reloaded: The gut microbota composition in conventional mice does not prevent from Campylobacter coli infection

“…One major reason for these severe immunopathological responses mounting in acute ulcerative enterocolitis is the absence of colonization resistance and the lack of IL-10 providing murine resistance to C. jejuni LOS [38,39]. In consequence, C. jejuni infected IL-10 -/mice display pronounced LOS induced and TLR-4-dependent innate and adaptive immune responses that are not restricted to the intestinal tract, but can also be observed in extra-intestinal including systemic compartments [19,30,[40][41][42][43][44][45][46]. Based on the results of this study, we therefore plan to include more C. coli strains from different sources (environmental, animal, human) in our future in vivo infection studies.…”

New and alternative strategies for the prevention, control, and treatment of antibiotic-resistant Campylobacter

“…However, several studies have been conducted using cell cultures or mouse models. [81][82][83][84] These studies demonstrated probiotic products, such as Bacillus and Lactobacillus, reduced Campylobacter colonization in mice, C. jejuni invasion into cultured human epithelial cells, or release of pro-inflammatory cytokines from Campylobacter-infected cells. Since chicken is a major reservoir for Campylobacter, there have been active efforts in developing probiotics to reduce Campylobacter colonization in poultry.…”

Intestinal microbiota changes in mice lacking pituitary adenylate cyclase activating polypeptide (PACAP) — bifidobacteria make the difference

“…Very recently, we were able to demonstrate the extensive impact of VSL#3 treatment on mucosal, peripheral, and systemic innate and adaptive immunity exerting beneficial anti-inflammatory effects in intestinal as well as systemic compartments of mice that had been subjected to broad-spectrum antibiotic treatment [ 27 ]. In addition, VSL#3 treatment was sufficient to attenuate intestinal, but also extra-intestinal including systemic pro-inflammatory responses upon murine infection with the enteropathogen Campylobacter jejuni [ 35 ].…”