Gut Susceptibility to Viral Invasion: Contributing Roles of Diet, Microbiota and Enteric Nervous System to Mucosal Barrier Preservation.

The gastrointestinal lumen is a rich source of eukaryotic and prokaryotic viruses which, together with bacteria, fungi and other microorganisms comprise the gut microbiota. Pathogenic viruses inhabiting this niche have the potential to induce local as well as systemic complications; among them, the viral ability to disrupt the mucosal barrier is one mechanism associated with the promotion of diarrhea and tissue invasion. This review gathers recent evidence showing the contributing effects of diet, gut microbiota and the enteric nervous system to either support or impair the mucosal barrier in the context of viral attack.

Ultrastructural and molecular characterization of non-Helicobacter pylori species in the gastric mucosa of naturally infected pigs

Infection by Helicobacter spp. has been associated with gastritis and ulcers in pigs and humans. Association between Helicobacter species and lesions can contribute to determine specific pathogenicity. The aim of this study was to describe ultrastructural aspects of Helicobacter spp. and identify Helicobacter species by PCR assay. Gastric samples from 13 naturally infected sows were analyzed. From these, 12 were positive for Helicobacter spp. 16S rRNA gene and seven were identified as H. suis. The species was not identified in five samples and all samples were negative for urease gene. The sequencing of rRNA gene of five samples showed similarity with H. suis and H. heilmannii type I. Seven samples positive for Helicobacter genus generated no sequenceable fragments. On ultrastructural study, three samples showed helical bacteria measuring 4 to 6 μm long, 0.5 to 0.8 μm width, 4 to 8 spirals and 2 to 6 bipolar flagella. Two samples showed bacteria measuring 9 to 10 μm in length, 0.5 μm width, 22 to 24 spirals and no flagella, characterizing Helicobacter non-H. pylori, but these samples were negative for H. suis. In conclusion, the results indicate that adult pigs are commonly infected by helical bacteria presenting different ultrastructural characteristics, suggesting that mixed infection is frequent.

Ultrastructural and molecular characterization of non-Helicobacter pylori species in the gastric mucosa of naturally infected pigs

Infection by Helicobacter spp. has been associated with gastritis and ulcers in pigs and humans. Association between Helicobacter species and lesions can contribute to determine specific pathogenicity. The aim of this study was to describe ultrastructural aspects of Helicobacter spp. and identify Helicobacter species by PCR assay. Gastric samples from 13 naturally infected sows were analyzed. From these, 12 were positive for Helicobacter spp. 16S rRNA gene and seven were identified as H. suis. The species was not identified in five samples and all samples were negative for urease gene. The sequencing of rRNA gene of five samples showed similarity with H. suis and H. heilmannii type I. Seven samples positive for Helicobacter genus generated no sequenceable fragments. On ultrastructural study, three samples showed helical bacteria measuring 4 to 6 μm long, 0.5 to 0.8 μm width, 4 to 8 spirals and 2 to 6 bipolar flagella. Two samples showed bacteria measuring 9 to 10 μm in length, 0.5 μm width, 22 to 24 spirals and no flagella, characterizing Helicobacter non-H. pylori, but these samples were negative for H. suis. In conclusion, the results indicate that adult pigs are commonly infected by helical bacteria presenting different ultrastructural characteristics, suggesting that mixed infection is frequent.(AU)

Evidence of Epstein-Barr virus association with gastric cancer and non-atrophic gastritis.

Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.

Epstein-Barr virus DNA associated with gastric adenocarcinoma and adjacent non-cancerous mucosa in patients from Manaus, Brazil.

Gastric cancer is one of most frequent causes of death in Brazil. The city of Manaus has one of the highest incidences of this disease in Brazil. The Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that is classified as a group 1 carcinogen by the International Agency for Research on Cancer. We obtained biopsies from 6 control subjects and 10 patients with gastric carcinomas living in Manaus. In the patients, the samples were taken from tumors and from adjacent non-cancerous mucosa. These samples were screened for EBV DNA by PCR to amplify the 288-bp fragments from the Bam M region. The EBV DNA was detected in 8 of the 10 tumor cases and in none of the 6 control subjects. In the positively identified samples, EBV DNA was detected in five corresponding resection margins. Previous research indicated only a weak association between EBV and gastric cancer. We suggest that EBV should be considered as a risk factor for gastric adenocarcinomas in Manaus.

Helicobacter pylori gastritis in children is associated with a regulatory T-cell response.

BACKGROUND & AIMS: Helicobacter pylori infection in children infrequently causes gastroduodenal mucosal ulceration. Because H pylori induces T-cell dependent gastric inflammation in adults and T regulatory (Treg) cells suppress T-cell-dependent pathology, we evaluated gastric histopathology and Treg cell responses in H pylori-infected children and adults. METHODS: Gastric tissue from 36 children and 79 adults with abdominal symptoms in Santiago, Chile, was evaluated prospectively for H pylori bacteria and histopathology using the Sydney classification and Treg responses using immunoassay, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: Eighteen (50%) of the children and 51 (65%) of the adults were infected with H pylori. Children and adults were colonized with similar levels of H pylori. However, the level of gastritis in the children was reduced substantially compared with that of the adults (P < .05). Coincident with reduced gastric inflammation, the number of Treg cells and levels of Treg cytokines (transforming growth factor [TGF]-beta1 and interleukin-10) were increased markedly in the gastric mucosa of H pylori-infected children compared with that of infected adults (P < .03 and < .05, respectively). Also, H pylori infection in the children was associated with markedly increased levels of gastric TGF-beta1 and interleukin-10 messenger RNA. Importantly, gastric TGF-beta1 in H pylori-infected children localized predominantly to mucosal CD25(+) and Foxp3(+) cells, indicating a Treg source for the TGF-beta1. CONCLUSIONS: Gastric pathology is reduced and local Treg cell responses are increased in H pylori-infected children compared with infected adults, suggesting that gastric Treg cell responses down-regulate the inflammation and ulceration induced by H pylori in children.

[Chronic active plasmacytic gastritis associated with cytomegalovirus]. / Gastritis plasmocelular crónica activa asociada a citomegalovirus.

Chronic active plasmacytic gastritis (CAPG) is characterized by the presence of chronic inflammatory cell infiltrates, mainly formed by plasma cells, involving the neck of gastric glands. This lesion, as well as Ménétrier disease, has been linked to cytomegalovirus (CMV). To test this association we evaluated the foveolar/glandular (F/G) index and the presence of CMV DNA (desoxirribonucleic acid) by means of polymerase chain reaction (PCR) in 12 cases of CAPG and 13 controls. Cases exhibiting CAPG included 2 with Ménétrier disease, 6 with foveolar hyperplasia, and 3 with normal foveolar/glandular (F/G) index. None showed either lymphocytic gastritis or CMV inclusions. Three CAPG cases were associated with gastric carcinoma. The F/G index was less than 1 in all controls. Eleven out of the 12 cases with CAPG showed amplification for CMV DNA while all controls were negative. Findings suggest a very close association, probably in progressive stages, between CMV infection, CAPG, foveolar hyperplasia (with or without Ménétrier disease) and gastric carcinoma. CAPG might be a histologic marker for CMV infection in the germinative zone of the neck of gastric glands. These findings resemble those of hepatitis B virus (HBV) infection, chronic hepatitis, cirrhosis, and hepatocellular carcinoma saga.

Gastritis plasmocelular crónica activa asociada a citomegalovirus / Chronic active plasmacytic gastritis associated with cytomegalovirus

La gastritis plasmocelular crónica activa (GPCA) se caracteriza por la presencia de infiltrados inflamatorios crónicos predominantemente plasmocelulares que comprometen las células del cuello de las glándulas gástricas. Tanto la GPCA como la gastropatía de Ménétrier han sido vinculadas con el citomegalovirus (CMV). Con el propósito de probas esta asociación, se evaluó la relación fovéolo-glandular (F/G) y se determinó la presencia del AND (ácido desoxirribonucleico) del CMV mediante PCR (reacción en cadena de polimerasa) en 12 casos y 13 controles. Los ejemplos de GPCA presentaron enfermedad de Ménétrier en 2 casos; hiperplasia foveolar, en 6 casos, y relación F/G conservada, en 3 casos. En ninguno visualizaron imágenes de gastritis linfocitaria, ni alteraciones citopáticas por CMV. Tres casos se asociaron con carcinoma gástrico. La relación F/G fue menor de 1 en todos los controles. Once de los 12 casos con GPCA mostraron amplificación para le AND del CMV y los 13 controles fueron negativos. Los hallazgos sugieren una fuerte asociación, posiblemente secuencial, entre la infección por el CMV, la GPCA, la hiperplasia foveolar (con o sin desarrollo de enfermedad de Ménétrier) y el carcinoma gástrico. La GPCA podría representar un marcador histológico de la presencia de CMV en la zona germinativa de los cuellos glandulares. La propuesta es paralela a los hallazgos, las lesiones y la secuencia observables en la infección hepática por VHB (irus de hepatitis B), con el desarrollo de hepatitis crónica, cirrosis y hepatocarcinoma.

Gastritis plasmocelular crónica activa asociada a citomegalovirus / Chronic active plasmacytic gastritis associated with cytomegalovirus

La gastritis plasmocelular crónica activa (GPCA) se caracteriza por la presencia de infiltrados inflamatorios crónicos predominantemente plasmocelulares que comprometen las células del cuello de las glándulas gástricas. Tanto la GPCA como la gastropatía de Ménétrier han sido vinculadas con el citomegalovirus (CMV). Con el propósito de probas esta asociación, se evaluó la relación fovéolo-glandular (F/G) y se determinó la presencia del AND (ácido desoxirribonucleico) del CMV mediante PCR (reacción en cadena de polimerasa) en 12 casos y 13 controles. Los ejemplos de GPCA presentaron enfermedad de Ménétrier en 2 casos; hiperplasia foveolar, en 6 casos, y relación F/G conservada, en 3 casos. En ninguno visualizaron imágenes de gastritis linfocitaria, ni alteraciones citopáticas por CMV. Tres casos se asociaron con carcinoma gástrico. La relación F/G fue menor de 1 en todos los controles. Once de los 12 casos con GPCA mostraron amplificación para le AND del CMV y los 13 controles fueron negativos. Los hallazgos sugieren una fuerte asociación, posiblemente secuencial, entre la infección por el CMV, la GPCA, la hiperplasia foveolar (con o sin desarrollo de enfermedad de Ménétrier) y el carcinoma gástrico. La GPCA podría representar un marcador histológico de la presencia de CMV en la zona germinativa de los cuellos glandulares. La propuesta es paralela a los hallazgos, las lesiones y la secuencia observables en la infección hepática por VHB (irus de hepatitis B), con el desarrollo de hepatitis crónica, cirrosis y hepatocarcinoma. (AU)

Gastrointestinal immune responses in HIV infected subjects

The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

Gastrointestinal immune responses in HIV infected subjects.

The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

Cytomegalovirus-associated Ménétrier's disease in adults. Demonstration by polymerase chain reaction (PCR).

Ménétrier's disease (MD) is a rare form of hypertrophic or hyperplastic gastropathy characterized by conspicuous thickening of the gastric mucosal folds and foveolar (crypt) hyperplasia. We examined the presence of cytomegalovirus (CMV) in 2 cases of MD in adults, one associated with gastric carcinoma, using the polymerase chain reaction (PCR). None of the cases showed intranuclear inclusions consistent with CMV infection. Both revealed, besides the features of MD, a peculiar pattern of "chronic active plasmacellular gastritis". Although the samples had been stored in formalin for more than 10 years CMV-DNA was recovered with good yield from both samples. The demonstration of CMV in MD in adults may helps to explain present knowledge of the complex relationships between this virus and gastric mucosa, and strongly suggests a pathogenetic role of the virus with variable phenotypic expression along the years.

Cytomegalovirus-associated Ménétrier's disease in adults: demonstration by polymerase chain reaction (PCR)

Ménétrier's disease (MD) is a rare form of hypertrophic or hyperplastic gastropathy characterized by conspicuous thickening of the gastric mucosal folds and foveolar (crypt) hyperplasia. We examined the presence of cytomegalovirus (CMV) in 2 cases of MD in adults, one associated with gastric carcinoma, using the polymerase chain reaction (PCR). None of the cases showed intranuclear inclusions consistent with CMV infection. Both revealed, besides the features of MD, a peculiar pattern of "chronic active plasmacellular gastritis". Although the samples had been-stored in formalin for more than 10 years CMV-DNA was recovered with good yield from both samples. The demonstration of CMV in MD in adults may helps to explain present knowledge of the complex relationships between this virus and gastric mucosa, and strongly suggests a pathogenetic role of the virus with variable phenotypic expression along the years.

Cytomegalovirus-associated Ménétriers disease in adults: demonstration by polymerase chain reaction (PCR)

Ménétriers disease (MD) is a rare form of hypertrophic or hyperplastic gastropathy characterized by conspicuous thickening of the gastric mucosal folds and foveolar (crypt) hyperplasia. We examined the presence of cytomegalovirus (CMV) in 2 cases of MD in adults, one associated with gastric carcinoma, using the polymerase chain reaction (PCR). None of the cases showed intranuclear inclusions consistent with CMV infection. Both revealed, besides the features of MD, a peculiar pattern of "chronic active plasmacellular gastritis". Although the samples had been-stored in formalin for more than 10 years CMV-DNA was recovered with good yield from both samples. The demonstration of CMV in MD in adults may helps to explain present knowledge of the complex relationships between this virus and gastric mucosa, and strongly suggests a pathogenetic role of the virus with variable phenotypic expression along the years.(AU)