Summary To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA‐6475) in gnotobiotic B6.129P2‐IL‐10tm1Cgn (IL‐10−/−) mice. No typhlocolitis developed in germ‐free controls (n = 21) or in L. reuteri (n = 8) or H. hepaticus (n = 18) mono‐associated mice for 20 weeks post‐infection. As positive controls, three specific pathogen‐free IL‐10−/− mice dosed with H. hepaticus developed severe typhlocolitis within 11 weeks. Because L. reuteri PTA‐6475 has anti‐inflammatory properties in vitro, it was unexpected to observe significant typhlocolitis (P < 0·0001) in mice that had been infected with L. reuteri followed in 1 week by H. hepaticus (n = 16). The H. hepaticus colonization was not affected through 20 weeks post‐infection but L. reuteri colonization was lower in co‐infected compared with L. reuteri mono‐associated mice at 8–11 weeks post‐infection (P < 0·05). Typhlocolitis was associated with an increased T helper type 1 serum IgG2c response to H. hepaticus in co‐infected mice compared with H. hepaticus mono‐associated mice (P < 0·005) and similarly, mRNA expression in caecal–colonic tissue was elevated at least twofold for chemokine ligands and pro‐inflammatory interleukin‐1α (IL‐1α), IL‐1β, IL‐12 receptor, tumour necrosis factor‐α and inducible nitric oxide synthase. Anti‐inflammatory transforming growth factor‐β, lactotransferrin, peptidoglycan recognition proteins, Toll‐like receptors 4, 6, 8 and particularly 9 gene expression, were also elevated only in co‐infected mice (P < 0·05). These data support that the development of typhlocolitis in H. hepaticus‐infected IL‐10−/− mice required co‐colonization with other microbiota and in this study, required only L. reuteri. Although the effects other microbiota may have on H. hepaticus virulence properties remain speculative, further investigations using this gnotobiotic model are now possible.
We recently described helicobacter-associated progressive, proliferative, and dysplastic typhlocolitis in aging (18-to 24-month-old) Syrian hamsters. Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified. The presence of Helicobacter genusspecific DNA was noted by PCR in cecal and paraffin-embedded liver samples from aged hamsters by the use of Helicobacter-specific PCR primers. By 16S rRNA analysis, the Helicobacter sp. isolated from the liver tissue was identical to the cecal isolates from hamsters. The six hamster 16S rRNA sequences form a genotypic cluster most closely related to Helicobacter sp. Flexispira taxon 8, part of the Helicobacter bilis/H. cinaedi group. Livers from aged helicobacter-infected hamsters showed various stages of predominantly portocentric and, to a lesser extent, perivenular fibrosis. Within nodules, there was cellular atypia consistent with nodular dysplasia. The livers also exhibited a range of chronic active portal/interface and lobular inflammation, with significant portal hepatitis being present. The inflammation was composed of a mixture of lymphocytes, neutrophils, and macrophages, indicative of its chronic-active nature in these aged hamsters infected with Helicobacter spp. The isolation of novel Helicobacter spp., their identification by PCR from the diseased livers of aged hamsters, and their taxonomic classification as belonging to the Helicobacter bilis cluster strengthen the argument that H. bilis and closely related Helicobacter spp. play an etiological role in hepatobiliary disease in both animals and humans.We recently described progressive, proliferative, and dysplastic typhlocolitis in aging (18-to 24-month-old) Syrian hamsters (31). The lesions in these hamsters were more severe in the older animals aged 7 to 24 months than in the younger, 1-to 6-month-old hamsters. The presence of Helicobacter spp. in the large bowel of all 24 hamsters included in the study was confirmed by culture and Helicobacter-specific PCR (31). Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified in this study (31). Enterohepatic Helicobacter spp. are associated with the development of inflammatory bowel disease in mice and, as determined more recently, humans (2, 18, 27, 51). These helicobacters can also induce hepatitis and hepatocellular carcinoma in susceptible strains of mice (1,14,19). We undertook a study to examine in detail the histological profile of the livers of hamsters aged 18 to 24 months and to determine whether Helicobacter sp. DNA was present in their livers (31). In addition, we purchased a small number of 6-month-old hamsters from the same vendor which originally supplied the aged hamsters and examined them for the presence of Helicobacter spp. in their intestines and liver and whether inflammation was associated with the presence of Helicobacter spp. in these target tissues. We document t...
Helicobacter cinaedi, a common human intestinal bacterium, has been implicated in various enteric and systemic diseases in normal and immunocompromised patients. Protection against oxidative stress is a crucial component of bacterium-host interactions. Alkyl hydroperoxide reductase C (AhpC) is an enzyme responsible for detoxification of peroxides and is important in protection from peroxide-induced stress. H. cinaedi possesses a single ahpC, which was investigated with respect to its role in bacterial survival during oxidative stress. The H. cinaedi ahpC mutant had diminished resistance to organic hydroperoxide toxicity but increased hydrogen peroxide resistance compared with the wild-type (WT) strain. The mutant also exhibited an oxygen-sensitive phenotype and was more susceptible to killing by macrophages than the WT strain. In vivo experiments in BALB/c and BALB/c interleukin-10 (IL-10) ؊/؊ mice revealed that the cecal colonizing ability of the ahpC mutant was significantly reduced. The mutant also had diminished ability to induce bacterium-specific immune responses in vivo, as shown by immunoglobulin (IgG2a and IgG1) serum levels. Collectively, these data suggest that H. cinaedi ahpC not only contributes to protecting the organism against oxidative stress but also alters its pathogenic properties in vivo.
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