Authors:Claudia Genger, Sigri Kløve, Soraya Mousavi, Stefan Bereswill and Markus M. Heimesaat
, are protected from stable C. jejuni colonization even following peroral infection with high bacterial loads [ 17 ]. This physiological colonizationresistance provided by the intact complex murine gut microbiota is abrogated upon broad
Authors:S. Bereswill, R. Plickert, A. Fischer, A. A. Kühl, C. Loddenkemper, A. Batra, B. Siegmund, U. B. Göbel and M. M. Heimesaat
Enterocolitis caused by Campylobacter jejuni-infections represents an important socioeconomic burden worldwide. Recent results from novel murine infection models reveal that the intestinal microbiota is essential for maintaining colonization resistance against C. jejuni. We extended these studies to investigate the role of nutrition and obesity in susceptibility to C. jejuni-infection. Gnotobiotic (GB) mice generated by antibiotic treatment, which were fed with a human cafeteria diet (CAF), as well as obese (ob/ob) mice with a conventional microbiota harbored higher Escherichia coli loads in their colon as compared to respective controls. Following oral infection, C. jejuni 43431 ATCC readily colonized the intestines of CAF and ob/ob mice, whereas GB mice fed with a standard chow (MUD) eradicated the pathogen within days. Furthermore, live C. jejuni translocated into mesenteric lymph nodes of CAF, but not MUD mice. Strikingly, stably infected animals developed enterocolitis as indicated by increased numbers of immune and apoptotic cells in the colon in situ.
We conclude that a specific human diet and obesity render mice susceptible to C. jejuni infection. The corresponding murine models are excellently suited for the study of C. jejuni pathogenesis and will help to get further insights into interplays between C. jejuni, microbiota, diet, obesity and immunity.
Authors:L.-M. Haag, A. Fischer, B. Otto, U. Grundmann, A. A. Kühl, U. B. Göbel, S. Bereswill and Markus M. Heimesaat
Campylobacter (C.) jejuni is among the leading bacterial agents causing enterocolitis worldwide. Despite the high prevalence of C. jejuni infections and its significant medical and economical consequences, intestinal pathogenesis is poorly understood. This is mainly due to the lack of appropriate animal models. In the age of 3 months, adult mice display strong colonization resistance (CR) against C. jejuni. Previous studies underlined the substantial role of the murine intestinal microbiota in maintaining CR. Due to the fact that the host-specific gut flora establishes after weaning, we investigated CR against C. jejuni in 3-week-old mice and studied intestinal and extra-intestinal immunopathogenesis as well as age dependent differences of the murine colon microbiota. In infant animals infected orally immediately after weaning C. jejuni strain B2 could stably colonize the gastrointestinal tract for more than 100 days. Within six days following infection, infant mice developed acute enterocolitis as indicated by bloody diarrhea, colonic shortening, and increased apoptotic cell numbers in the colon mucosa. Similar to human campylobacteriosis clinical disease manifestations were self-limited and disappeared within two weeks. Interestingly, long-term C. jejuni infection was accompanied by distinct intestinal immune and inflammatory responses as indicated by increased numbers of T- and B-lymphocytes, regulatory T-cells, neutrophils, as well as apoptotic cells in the colon mucosa. Strikingly, C. jejuni infection also induced a pronounced influx of immune cells into extra-intestinal sites such as liver, lung, and kidney. Furthermore, C. jejuni susceptible weaned mice harbored a different microbiota as compared to resistant adult animals. These results support the essential role of the microflora composition in CR against C. jejuni and demonstrate that infant mouse models resemble C. jejuni mediated immunopathogenesis including the characteristic self-limited enterocolitis in human campylobacteriosis. Furthermore, potential clinical and immunological sequelae of chronic C. jejuni carriers in humans can be further elucidated by investigation of long-term infected infant mice. The observed extraintestinal disease manifestations might help to unravel the mechanisms causing complications such as reactive arthritis or Guillain-Barré syndrome.
Authors:Eliane von Klitzing, Stefan Bereswill and Markus M. Heimesaat
, Stein AJ , Casey SW , Que JU : Protective role of intestinal flora against infection with Pseudomonas aeruginosa in mice: influence of antibiotics on colonizationresistance . Infect Immun 47 , 118 – 122
Authors:Markus M. Heimesaat, Ursula Grundmann, Marie E. Alutis, André Fischer, Ulf B. Göbel and Stefan Bereswill
, Fischer A , Otto B , Plickert R , Kuhl AA , Gobel UB , Bereswill S , Heimesaat MM : Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonizationresistance against