The Host-Specific Intestinal Microbiota Composition Impacts Campylobacter coli Infection in a Clinical Mouse Model of Campylobacteriosis.

Markus M Heimesaat,Soraya Mousavi,Stefan Bereswill,Dennis Weschka,Claudia Genger,Sigri Kløve

doi:10.3390/pathogens9100804

Abstract

Human Campylobacter-infections are progressively rising globally. However, the molecular mechanisms underlying C. coli–host interactions are incompletely understood. In this study, we surveyed the impact of the host-specific intestinal microbiota composition during peroral C. coli infection applying an established murine campylobacteriosis model. Therefore, microbiota-depleted IL-10−/− mice were subjected to peroral fecal microbiota transplantation from murine versus human donors and infected with C. coli one week later by gavage. Irrespective of the microbiota, C. coli stably colonized the murine gastrointestinal tract until day 21 post-infection. Throughout the survey, C. coli-infected mice with a human intestinal microbiota displayed more frequently fecal blood as their murine counterparts. Intestinal inflammatory sequelae of C. coli-infection could exclusively be observed in mice with a human intestinal microbiota, as indicated by increased colonic numbers of apoptotic epithelial cells and innate as well as adaptive immune cell subsets, which were accompanied by more pronounced pro-inflammatory cytokine secretion in the colon and mesenteric lymph nodes versus mock controls. However, in extra-intestinal, including systemic compartments, pro-inflammatory responses upon pathogen challenge could be assessed in mice with either microbiota. In conclusion, the host-specific intestinal microbiota composition has a profound effect on intestinal and systemic pro-inflammatory immune responses during C. coli infection.

Highlights

Campylobacter infections represent frequent causes of human enteritis with rising prevalence worldwide
In order to assess the impact of the host-specific intestinal microbiota on C. coli infection and subsequent inflammatory responses, microbiota-depleted IL-10−/− mice were perorally subjected to fecal microbiota transplantations (FMT) from human or murine donors on three occasions
Upon necropsy on day 21 p.i., we quantitated C. coli alongside the gastrointestinal tract and observed comparable loads in respective compartments with highest counts in the large intestines (Figure 4)

Summary

Introduction

Campylobacter infections represent frequent causes of human enteritis with rising prevalence worldwide. The majority of campylobacteriosis cases are attributed to Campylobacter jejuni and Campylobacter coli [1,2], and pathogen-induced clinical symptoms are characterized by watery or bloody, inflammatory diarrhea, abdominal pain, and fever [3,4]. Primary campylobacteriosis triggers long-term post-infectious sequelae, such as Guillain-Barré syndrome, reactive arthritis, and chronic inflammatory intestinal illnesses, including coeliac disease, irritable bowel syndrome, and chronic inflammatory bowel diseases [4,5,6]. The main mode of human Campylobacter infections is ingestion of contaminated water, milk and undercooked meat derived from livestock, mostly chickens and other poultry. C. coli, for instance, have been found in swine and sheep at high frequencies [9,11,12]

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Conclusion