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

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.

Therapeutic Oral Application of Carvacrol Alleviates Acute Campylobacteriosis in Mice Harboring a Human Gut Microbiota

“…Previous studies also revealed that host susceptibility for and resistance against distinct enteropathogens including C. jejuni [49], Campylobacter coli [50], and Salmonella enterica [51] are determined by the host-specific intestinal microbiota. In order to elucidate the triangular relationship between enteropathogens on one side and immunity and the human gut microbiota on the other (host) side, we here tested carvacrol in IL-10 −/− mice harboring a human gut microbiota by subjecting secondary abiotic mice to oral transplantation of a fecal microbiota from human donors.…”

Immune-Mediated Aggravation of the Campylobacter concisus-Induced Epithelial Barrier Dysfunction

“…Such activation of macrophages with migration into the rectal epithelium was also observed in vivo in an ultrastructural analysis on Campylobacter spp.-infected patients with acute colitis [ 42 ]. Furthermore, in secondary abiotic IL-10 -/- mice challenged with human fecal microbiota, peroral C. coli infection promoted activation of macrophages in conjunction with the increased TNF-α secretion in colonic tissues 21 days post infection [ 43 ], a finding which supports the view of the immune activation being a central mechanism of the functional defects following the infection. In our present in vitro study, we also observed an activation of M1-macrophage-like THP-1 cells 48 h following C. concisus infection depicted through an increase in cell proliferation rate at different ranges of MOI from 25 up to 200 ( Figure S2B ).…”

Oral treatment of human gut microbiota associated IL-10−/− mice suffering from acute campylobacteriosis with carvacrol, deferoxamine, deoxycholic acid, and 2-fucosyl-lactose

“…Previous studies also revealed that the host-specific intestinal microbiota impacts the host's susceptibility to and resistance against distinct enteropathogens including C. jejuni , Campylobacter coli (Heimesaat et al, 2020), and Salmonella enterica (Chung et al, 2012). In order to elucidate the triangular relationship between enteropathogens on one side and the murine immunity and human gut microbiota on the other, the host side, we generated a human gut microbiota associated (hma) mouse model for C. jejuni induced inflammation.…”