Four cases of non-Helicobacter pylori Helicobacter-infected gastritis with duodenal spiral bacilli.

BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) is rarely detected in duodenal mucosa due to its preference for slightly acidic environments. Here, we report four cases of NHPH-infected gastritis with duodenal spiral bacilli, potentially NHPH, indicating the possibility of duodenal mucosal infection. CASE PRESENTATION: In every case, gastric mucosa showed endoscopic findings characteristic of NHPH-infected gastritis, and a mucosal biopsy was taken from the duodenal bulb; spiral bacilli were identified under microscopy using Giemsa staining. Case 1, a 46-year-old man, had diffuse spotty redness, mucosal edema, and multiple tiny erosions in the duodenal bulb, along with larger erosions in the second portion of the duodenum upon endoscopic examination. Histopathologically, moderate infiltration of mononuclear cells and neutrophils in the lamina propria and gastric epithelial metaplasia were observed. Case 2, a 54-year-old man, showed an elevated lesion, 1 cm in diameter, with multiple red spots and a few tiny erosions in the duodenal bulb. Histopathologically, mild inflammatory cell infiltration and gastric epithelial metaplasia were observed. In Case 3, a 52-year-old man, endoscopy revealed a flat elevated lesion, 7 mm in diameter, with multiple red spots and a few tiny erosions in the anterior wall of the duodenal bulb. Histopathologically, we observed moderate inflammatory cell infiltration in the gastric antrum and gastric epithelial metaplasia in the duodenal bulb. Case 4, a 40-year-old man, showed mild spotty redness in the duodenal bulb. Histopathologically, mild mononucleocyte infiltration and gastric epithelial metaplasia were observed. A single spiral bacillus was observed in Case 4 by microscopy. In all but Case 2, Helicobacter suis was identified in the gastric juice by polymerase chain reaction analysis. CONCLUSIONS: Spiral bacilli resembling NHPH may infect the duodenal mucosa, particularly the bulb, causing inflammation. Gastric contents entering the duodenum may reduce the intraduodenal pH, promoting NHPH survival and proliferation.

Helicobacter bilis Contributes to the Occurrence of Inflammatory Bowel Disease by Inducing Host Immune Disorders.

Gut microbiota coevolve with humans to achieve a symbiotic relationship, which ultimately leads to physiological homeostasis. A variety of diseases can occur once this balance is disrupted. Helicobacter bilis (H. bilis) is an opportunistic pathogen in humans, triggering multiple diseases, including inflammatory bowel disease (IBD). IBD is a chronic immunologically mediated inflammation of the human gastrointestinal tract, and its occurrence is closely related to the gut microbiota. Several studies have demonstrated that H. bilis colonization is associated with IBD, and its mechanism is related to host immunity. However, few studies have investigated these mechanisms of action. Therefore, this article is aimed at reviewing these studies and summarizing the mechanisms of H. bilis-induced IBD from two perspectives: adaptive immunity and innate immunity. Furthermore, this study provides a preliminary discussion on treating H. bilis-related IBD. In addition, we also demonstrated that H. bilis played an important role in promoting the carcinogenesis of IBD and discussed its mechanism.

A report of nonexistence of the non-Helicobacter pylori Helicobacter species in Iranian patients suffering from inflammatory bowel disease.

Inflammatory bowel disease is a chronic, relapsing-remitting gastrointestinal disorder which has become a serious global concern, and it imposes a great degree of health and economic burdens on communities worldwide. Although the presence of non-Helicobacter pylori Helicobacter (NHPH) microorganisms has been reported in various gastrointestinal disorders, their putative role in the pathogenesis of IBD has been a matter of controversy. The present study aimed to investigate the existence of gastric and enterohepatic NHPHs and their probable coinfection with H. pylori in IBD. Totally, 168 clinical specimens including 70 colonic biopsies and 98 fecal specimens were obtained from IBD patients. Genomic DNA was extracted from all samples, and its quality and concentration were assessed by ß-globin PCR and spectrophotometry. The Helicobacter genus-specific PCR was performed using 16S rRNA gene. All samples were also tested for H. pylori infection by PCR of ureC gene fragment (glmM). The presence of NHPH was examined by using species-specific PCR assays. Based on PCR results, H. pylori was detected in 12.9% and 3.1% of colonic biopsies and fecal specimens, respectively. However, no statistically significant correlation was observed (P value > 0.05). We failed to find NHPH in both colonic biopsies and fecal specimens from IBD patients. Despite the fact that none of the IBD patients harbored the NHPH in the current work, further cohorts with larger sample size are required to determine the possible relationship between NHPH infection and IBD pathogenesis.

Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation.

Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103+ gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacter-specific T cell receptor (TCR) transgenic mouse lines, we found that both CD103+ and CD103- migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103+ migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103- DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is 'dominant', necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.

Altered gut microbiota correlated with systemic inflammation in children with Kawasaki disease.

Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD. The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation. Totally 30 KD children were enrolled and followed up for 6 months, with another group of 30 age- and sex-matched healthy children as controls. Phylotype profiles of fecal microbial communities were analyzed using 16S rRNA gene sequencing. Serum inflammatory markers were detected by flow cytometer. We showed that KD children exhibited a significant reduction in fecal microbial diversity in the acute phase compared with the healthy controls. Enterococcus, Acinetobacter, Helicobacter, Lactococcus, Staphylococcus and Butyricimonas in acute KD children were significantly higher than the healthy children. Levels of systemic inflammation biomarkers, including IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ, were significantly elevated in the acute KD children. Altered microbiota genera Enterococcus and Helicobacter abundances were shown to be correlated positively with IL-6, which were never previously reported in KD. This study suggested that gut microbiota alteration is closely associated with systemic inflammation, which provides a new perspective on the etiology and pathogenesis of KD.

Interactions of Segmented Filamentous Bacteria (Candidatus Savagella) and bacterial drivers in colitis-associated colorectal cancer development.

Colorectal cancer (CRC) risk is influenced by host genetics, sex, and the gut microbiota. Using a genetically susceptible mouse model of CRC induced via inoculation with pathobiont Helicobacter spp. and demonstrating variable tumor incidence, we tested the ability of the Th17-enhancing commensal Candidatus Savagella, more commonly denoted as Segmented Filamentous Bacteria (SFB), to influence the incidence and severity of colitis-associated CRC in male and female mice. To document the composition of the gut microbiota during CRC development and identify taxa associated with disease, fecal samples were collected before and throughout disease development and characterized via 16S rRNA sequencing. While there were no significant SFB-dependent effects on disease incidence or severity, SFB was found to exert a sex-dependent protective effect in male mice. Furthermore, SFB stabilized the GM against Helicobacter-induced changes post-inoculation, resulting in a shift in disease association from Helicobacter spp. to Escherichia coli. These data support sex-dependent SFB-mediated effects on CRC risk, and highlight the complex community dynamics within the GM during exposure to inflammatory pathobionts.

Helicobacter spp. in Experimental Models of Colitis.

The colonization of body surfaces, notably of the intestine, by a complex microbiota is generally highly mutualistic, where vital functions are provided by the commensal microbiota to the host, including the synthesis of vitamins, the degradation of complex polysaccharides into small chain fatty acids (which are essential for the maintenance of the intestinal epithelial barrier), and, finally, the outcompetition of pathogens that accidentally gain access to the body ("colonization resistance") (Chow et al. 2011; Backhed 2005). However, under certain conditions, such as changes of environmental factors in a genetically predisposed host, some of these normally symbiotic bacteria may act as pathogens and induce pathologies. Hence, the term "pathobionts" was coined for these bacterial species with ambiguous biological properties (Round et al. 2009).

Shape of gastrointestinal immunity with non-genetically modified Lactococcus lactis particles requires commensal bacteria and myeloid cells-derived TGF-ß1.

Heat-killed probiotics or microbial autologous components show multiple activities on modulating host immune responses towards tolerance or vice versus aggressiveness. Gram-positive enhancer matrix particles (GEMs), the non-genetically modified particles which composed of the cell wall derived from Lactococcus lactis (L. lactis), were used as a typical microbial molecule to investigate the mechanism of opposite immune responses generated in disparate scenarios. The results of stool 16S rRNA Illumina sequencing suggested that the overwhelming number of mice pre-administered with GEMs showed the expansion of Bacteroidetes but contraction of Verrucomicrobia. Co-administration GEMs and antibiotics could preserve the microbial diversity, even though the abundance of gut microbes was largely depleted by antibiotics. Additionally, dendritic cells (DCs) from mice receiving GEMs rather than DCs that in vitro treated with GEMs induced the expansion of regulatory T cells (Tregs), witnessing the critical role of gut flora alteration. Importantly, this alteration provided protection to alleviate dextran sulfate sodium (DSS)-induced intestinal inflammation. On the other hand, in the context of Helicobacter felis (H. felis) infection, the mice pre-administrated with GEMs exhibited a comparably potent gastric immunity with the elevated expression of IFN-γ, IL-17, and multiple anti-microbial factors, leading to the reduced burden of H. felis. However, tolerance for both DSS-induced intestinal inflammation and immunity against H. felis was depleted in a mice model lacking of transforming growth factor-ß1 (TGF-ß1) in myeloid cells. These findings suggest that GEMs can modulate host immune responses bidirectionally according to context, and may serve as a supplement for antibiotic treatment.

Helicobacter infection in the hepatobiliary system and hepatic lesions: a possible association in dogs.

Helicobacter infection has been associated with hepatobiliary diseases in humans and animals. The aims of this study were to identify Helicobacter species in the hepatobiliary tract of dogs and to elucidate the possible association of these bacteria in liver diseases. Twenty-seven gastric and hepatobiliary samples were collected from 33 dogs with hepatic lesions and 17 dogs with no liver histological changes. Warthin-Starry staining, immunohistochemical assay, and PCR were performed to detect the presence of Helicobacter. Helicobacter genus was detected in 21.2% of the samples with hepatic lesions. The main lesion was chronic hepatitis. Immunohistochemistry revealed infection in liver (1/5) and gallbladder (1/3) 32 samples. The sequence analysis of seven amplicons of the 16S rRNA gene of Helicobacter genus from hepatobiliary samples showed 97.8 to 100% of nucleotide identity with gastric helicobacter. One amplicon of the ureA and ureB gene of Helicobacter genus from the stomach showed 89.1 to 90.7% nucleotide identity with H. heilmannii. The presence of Helicobacter genus in liver samples showing hepatic lesions suggests the involvement of these bacteria in the etiology of hepatobiliary disease in dogs. DNA sequences were similar to gastric Helicobacter species, reinforcing the hypothesis of bacterial translocation from the stomach to liver by the biliary pathway.

Defective IgA response to atypical intestinal commensals in IL-21 receptor deficiency reshapes immune cell homeostasis and mucosal immunity.

Despite studies indicating the effects of IL-21 signaling in intestinal inflammation, its roles in intestinal homeostasis and infection are not yet clear. Here, we report potent effects of commensal microbiota on the phenotypic manifestations of IL-21 receptor deficiency. IL-21 is produced highly in the small intestine and appears to be critical for mounting an IgA response against atypical commensals such as segmented filamentous bacteria and Helicobacter, but not to the majority of commensals. In the presence of these atypical commensals, IL-21R-deficient mice exhibit reduced numbers of germinal center and IgA+ B cells and expression of activation-induced cytidine deaminase in Peyer's patches as well as a significant decrease in small intestine IgA+ plasmablasts and plasma cells, leading to higher bacterial burdens and subsequent expansion of Th17 and Treg cells. These microbiota-mediated secondary changes in turn enhance T cell responses to an oral antigen and strikingly dampen Citrobacter rodentium-induced immunopathology, demonstrating a complex interplay between IL-21-mediated mucosal immunity, microbiota, and pathogens.

Enhanced locomotion, effective diffusion and trapping of undulatory micro-swimmers in heterogeneous environments.

Swimming cells and microorganisms must often move through complex fluids that contain an immersed microstructure such as polymer molecules or filaments. In many important biological processes, such as mammalian reproduction and bacterial infection, the size of the immersed microstructure is comparable to that of the swimming cells. This leads to discrete swimmer-microstructure interactions that alter the swimmer's path and speed. In this paper, we use a combination of detailed simulation and data-driven stochastic models to examine the motion of a planar undulatory swimmer in an environment of spherical obstacles tethered via linear springs to random points in the plane of locomotion. We find that, depending on environmental parameters, the interactions with the obstacles can enhance swimming speeds or prevent the swimmer from moving at all. We also show how the discrete interactions produce translational and angular velocity fluctuations that over time lead to diffusive behaviour primarily due to the coupling of swimming and rotational diffusion. Our results demonstrate that direct swimmer-microstructure interactions can produce changes in swimmer motion that may have important implications for the spreading of cell populations in or the trapping of harmful pathogens by complex fluids.

Opisthorchiasis-Induced Cholangiocarcinoma: How Innate Immunity May Cause Cancer.

Innate, inflammatory responses towards persistent Opisthorchis viverrini (OV) infection are likely to contribute to the development of cholangiocarcinoma (CCA), a liver cancer that is rare in the West but prevalent in Greater Mekong Subregion countries in Southeast Asia. Infection results in the infiltration of innate immune cells into the bile ducts and subsequent activation of inflammatory immune responses that fail to clear OV but instead may damage local tissues within the bile ducts. Not all patients infected with OV develop CCA, and so tumourigenesis may be dependent on multiple factors including the magnitude of the inflammatory response that is activated in infected individuals. The purpose of this review is to summarize how innate immune responses may promote tumourigenesis following OV infection and if such responses can be used to predict CCA onset in OV-infected individuals. It also hypothesizes on the role that Helicobacterspp., which are associated with liver fluke infections, may play in activation of the innate the immune system to promote tissue damage and persistent inflammation leading to CCA.

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.

Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM) is an established risk allele in CD. We have shown previously that conventionally raised (CV) mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1-/- mice were rederived into specific pathogen-free (SPF) and germ-free (GF) conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1-/- mice. Remarkably, in contrast to CV mice, SPF Irgm1-/- mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1-/- mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1-/- mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1-/- mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1-/- mice as a model to elucidate host-environment interactions that regulate mucosal homeostasis and intestinal inflammatory responses. Defining such interactions will be essential for developing novel preventative and therapeutic strategies for human CD.

Analysis of the association between density of Helicobacter spp and gastric lesions in dogs.

OBJECTIVE To evaluate the correlation between the density of native gastric Helicobacter spp and the presence of gastric lesions in dogs. ANIMALS 80 dogs of various breeds, sexes, and ages. PROCEDURES Gastroscopic and histologic examinations were performed for all dogs. Helicobacter spp were detected by combining evaluation of urease activity and results of bacteriologic culture, microscopic observation, and a 16S rRNA PCR assay. The density of Helicobacter-like organisms was evaluated with light microscopy by use of Warthin-Starry modified stain. Correlations were evaluated by use of the Spearman correlation analysis. RESULTS Gastritis was found in 55 of 80 dogs and classified as mild (n = 31), moderate (16), or severe (8). Of these 55 dogs, only 8 had clinical signs. Histologic examination revealed some degree of lymphocytic-plasmacytic infiltrate, mild eosinophilia, and neutrophilic inflammation in the lamina propria. Seventy-six dogs had positive results for Helicobacter spp. Helicobacter pylori DNA was not detected. Low density and homogeneous distribution of Helicobacter spp were observed in all gastric zones. CONCLUSIONS AND CLINICAL RELEVANCE A significant correlation between density of Helicobacter spp and gastroscopic or histologic lesions was not detected. These findings supported the contention that there is no correlation between general Helicobacter spp density or numbers and gastritis in dogs.

Helicobacter Infection Significantly Alters Pregnancy Success in Laboratory Mice.

Helicobacter spp. are gram-negative, helically shaped bacteria that cause gastric and enterohepatic infections in mammalian species. Although Helicobacter infection frequently is implicated to interfere with reproductive success, few experimental data support these claims. We therefore retrospectively investigated the effect of Helicobacter infection on murine pregnancy outcome after the identification of endemic Helicobacter infection in an animal research facility. Multiplex conventional PCR analysis was used to characterize Helicobacter infection status in one inbred and 2 transgenic strains of mice in 2 self-contained rooms assigned to the same investigator. Outcomes of timed-mating experiments were compared among Helicobacter spp.-infected and uninfected mice of the same strain; Helicobacter infection was eradicated from the colony through fostering with uninfected dams. Although Helicobacter infection affected fecundity in only one strain of transgenic mouse, the total number of embryos per gravid uterus was significantly reduced in C57BL/6J mice that were infected with a single Helicobacter species, H. typhlonius. Helicobacter infection was also associated with a significant increase in the number of resorbing embryos per uterus and significant decreases in pregnancy-associated weight gain relative to uninfected mice in C57BL6/J mice and one transgenic strain. Helicobacter spp.-infected mice of all tested strains exhibited higher frequency of intrauterine hemorrhaging relative to uninfected mice. These results indicate that naturally-acquired Helicobacter infection not only reduces the productivity of a research animal breeding colony, but also negatively impacts embryo health. Despite these deleterious effects, these data suggest that colonies can be rederived to be Helicobacter-free by Cesarean section and fostering with uninfected dams. This paper provides the first evidence that H. typhlonius infection is sufficient to interfere with reproductive success and embryo health of C57BL/6J mice. Animal research facilities should therefore implement Helicobacter spp. surveillance and control practices to avoid confounding experimental results and to improve breeding colony efficiency.

Helicobacter cinaedi bacteremia with cellulitis in a living-donor kidney transplant recipient identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a case report.

BACKGROUND: Helicobacter cinaedi causes bacteremia and cellulitis, mainly in immunocompromised patients. We report a rare case of H. cinaedi bacteremia with cellulitis in a living-donor kidney transplant recipient identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). A 54-year-old Asian man with IgA nephropathy underwent living-donor kidney transplantation 14 years previously. He was admitted to our hospital for evaluation of fever and multifocal cellulitis. H. cinaedi was isolated and identified from the patient's blood using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and gyrase subunit B-targeted polymerase chain reaction assays. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry has proven over the years to be a rapid and accurate universal method for the identification of microorganisms. CONCLUSIONS: The combined use of these detection methods enabled the appropriate administration of 6 weeks of antibiotic therapy. The patient recovered completely, with no recurrence.

Epithelial Coculture and l-Lactate Promote Growth of Helicobacter cinaedi under H2-Free Aerobic Conditions.

Helicobacter cinaedi is an emerging opportunistic pathogen associated with infections of diverse anatomic sites. Nevertheless, the species demonstrates fastidious axenic growth; it has been described as requiring a microaerobic atmosphere, along with a strong preference for supplemental H2 gas. In this context, we examined the hypothesis that in vitro growth of H. cinaedi could be enhanced by coculture with human epithelial cells. When inoculated (in Ham's F12 medium) over Caco-2 monolayers, the type strain (ATCC BAA-847) gained the ability to proliferate under H2-free aerobic conditions. Identical results were observed during coculture with several other monolayer types (LS-174T, AGS, and HeLa). Under chemically defined conditions, 40 amino acids and carboxylates were screened for their effect on the organism's atmospheric requirements. Several molecules promoted H2-free aerobic proliferation, although it occurred most prominently with millimolar concentrations of l-lactate. The growth response of H. cinaedi to Caco-2 cells and l-lactate was confirmed with a collection of 12 human-derived clinical strains. mRNA sequencing was next performed on the type strain under various growth conditions. In addition to providing a whole-transcriptome profile of H. cinaedi, this analysis demonstrated strong constitutive expression of the l-lactate utilization locus, as well as differential transcription of terminal respiratory proteins as a function of Caco-2 coculture and l-lactate supplementation. Overall, these findings challenge traditional views of H. cinaedi as an obligate microaerophile. IMPORTANCE: H. cinaedi is an increasingly recognized pathogen in people with compromised immune systems. Atypical among other members of its bacterial class, H. cinaedi has been associated with infections of diverse anatomic sites. Growing H. cineadi in the laboratory is quite difficult, due in large part to the need for a specialized atmosphere. The suboptimal growth of H. cinaedi is an obstacle to clinical diagnosis, and it also limits investigation into the organism's biology. The current work shows that H. cinaedi has more flexible atmospheric requirements in the presence of host cells and a common host-derived molecule. This nutritional interplay raises new questions about how the organism behaves during human infections and provides insights for how to optimize its laboratory cultivation.

Helicobacter saguini, a Novel Helicobacter Isolated from Cotton-Top Tamarins with Ulcerative Colitis, Has Proinflammatory Properties and Induces Typhlocolitis and Dysplasia in Gnotobiotic IL-10-/- Mice.

A urease-negative, fusiform, novel bacterium named Helicobacter saguini was isolated from the intestines and feces of cotton-top tamarins (CTTs) with chronic colitis. Helicobacter sp. was detected in 69% of feces or intestinal samples from 116 CTTs. The draft genome sequence, obtained by Illumina MiSeq sequencing, for H. saguini isolate MIT 97-6194-5, consisting of ∼2.9 Mb with a G+C content of 35% and 2,704 genes, was annotated using the NCBI Prokaryotic Genomes Automatic Annotation Pipeline. H. saguini contains homologous genes of known virulence factors found in other enterohepatic helicobacter species (EHS) and H. pylori These include flagellin, γ-glutamyl transpeptidase (ggt), collagenase, the secreted serine protease htrA, and components of a type VI secretion system, but the genome does not harbor genes for cytolethal distending toxin (cdt). H. saguini MIT 97-6194-5 induced significant levels of interleukin-8 (IL-8) in HT-29 cell culture supernatants by 4 h, which increased through 24 h. mRNAs for the proinflammatory cytokines IL-1ß, tumor necrosis factor alpha (TNF-α), IL-10, and IL-6 and the chemokine CXCL1 were upregulated in cocultured HT-29 cells at 4 h compared to levels in control cells. At 3 months postinfection, all H. saguini-monoassociated gnotobiotic C57BL/129 IL-10(-/-) mice were colonized and had seroconverted to H. saguini antigen with a significant Th1-associated increase in IgG2c (P < 0.0001). H. saguini induced a significant typhlocolitis, associated epithelial defects, mucosa-associated lymphoid tissue (MALT) hyperplasia, and dysplasia. Inflammatory cytokines IL-22, IL-17a, IL-1ß, gamma interferon (IFN-γ), and TNF-α, as well as inducible nitric oxide synthase (iNOS) were significantly upregulated in the cecal tissues of infected mice. The expression of the DNA damage response molecule γ-H2AX was significantly higher in the ceca of H. saguini-infected gnotobiotic mice than in the controls. This model using a nonhuman primate Helicobacter sp. can be used to study the pathogenic potential of EHS isolated from primates with naturally occurring inflammatory bowel disease (IBD) and colon cancer.

Comparison of in vivo confocal endomicroscopy with other diagnostic modalities to detect intracellular helicobacters.

Intracellular colonisation may serve as a protected niche where Helicobacter spp. organisms evade effective treatment. In dogs, non-Helicobacter pylori-helicobacters are frequently intracellular. Confocal endomicroscopy allows in vivo gastrointestinal imaging and has aided real-time identification of Helicobacter pylori and other intracellular and mucosally associated bacteria. The objectives of this study were: (1) to determine the utility of confocal endomicroscopy to identify non-Helicobacter pylori-helicobacters compared with other diagnostic modalities, and (2) to assess its ability to identify intracellular organisms. Fourteen clinically healthy dogs underwent standard gastroduodenoscopy followed by confocal endomicroscopy using topical acriflavine. Confocal images were obtained from at least five gastric sites. Endoscopic biopsies were obtained for histopathology, PCR and fluorescence in situ hybridisation (FISH). Methodologies were compared for their ability to determine the presence and spatial distribution of gastric helicobacters in dogs. Confocal endomicroscopy provided high quality images allowing in vivo identification of non-Helicobacter pylori-helicobacters in 13 dogs. Histopathology identified helicobacters in 11 dogs. Organisms were identified within the superficial gastric mucus and within gastric pits, and distribution throughout the stomach was diffuse and multi-focal. Confocal endomicroscopy findings correlated with PCR and FISH post-procedure analysis. Only FISH identified intracellular organisms, which were present in 13/14 dogs. Confocal endomicroscopy provided in vivo histology images and was capable of identifying non-Helicobacter pylori-helicobacters during gastroscopy, but was unable to identify intracellular organisms using the current fluorophore protocol.