Targeting hypoxia-inducible factor-1 alpha suppresses -induced gastric injury via attenuation of both -mediated microbial virulence and proinflammatory host responses.

-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of -induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans.

Bile Acid Sequestrant Use and Gastric Cancer: A National Retrospective Cohort Analysis.

Introduction: Bile acids have been implicated in gastric carcinogenesis. We hypothesized that bile acid sequestrant medication (BAM) use is associated with a lower gastric cancer (GC) incidence.

Methods: We assembled a cohort of veterans receiving longitudinal care within the Veterans Health Administration between 2000 and 2020 who completed testing for Helicobacterpylori .

actively suppresses innate immune nucleic acid receptors.

Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and confers the highest risk for this disease. Gastric innate immune effectors can either eliminate bacteria or mobilize adaptive immune responses including Toll-like receptors (TLRs), and cytosolic DNA sensor/adaptor proteins (e.

Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori-induced inflammation-driven gastric carcinogenesis.

Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions.

Modification of the Gastric Mucosal Microbiota by a Strain-Specific Helicobacter pylori Oncoprotein and Carcinogenic Histologic Phenotype.

is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer.

Carcinogenic Strains Selectively Dysregulate the Gastric Proteome, Which May Be Associated with Stomach Cancer Progression.

is the strongest risk factor for gastric cancer. Initial interactions between and its host originate at the microbial-gastric epithelial cell interface, and contact between and gastric epithelium activates signaling pathways that drive oncogenesis. One microbial constituent that increases gastric cancer risk is the pathogenicity island, which encodes a type IV secretion system that translocates the effector protein, CagA, into host cells.

Helicobacter pylori pathogen regulates p14ARF tumor suppressor and autophagy in gastric epithelial cells.

Infection with Helicobacter pylori is one of the strongest risk factors for development of gastric cancer. Although these bacteria infect approximately half of the world's population, only a small fraction of infected individuals develops gastric malignancies. Interactions between host and bacterial virulence factors are complex and interrelated, making it difficult to elucidate specific processes associated with H.

genetic diversification in the Mongolian gerbil model.

requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed genetic adaptation in the Mongolian gerbil model. This model is of particular interest because -infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration.

Helicobacter pylori Makes a Molecular Incision to Gain Epithelial Entry.

Helicobacter pylori type IV secretion system injects the oncoprotein CagA into epithelial cells to drive carcinogenesis. In this issue of Cell Host & Microbe, Tegtmeyer et al. (2017) show that a secreted bacterial protease disrupts apical-junctional complexes, paving the way for H.

Pan-genomic analyses identify key pathogenic loci modified by carcinogenic host microenvironments.

Objective: is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of to in vivo carcinogenic microenvironments results in genetic modification important for disease.

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration.

Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H.

The Mongolian Gerbil: A Robust Model of Helicobacter pylori-Induced Gastric Inflammation and Cancer.

The Mongolian gerbil is an efficient, robust, and cost-effective rodent model that recapitulates many features of H. pylori-induced gastric inflammation and carcinogenesis in humans, allowing for targeted investigation of the bacterial determinants and environmental factors and, to a lesser degree, host constituents that govern H. pylori-mediated disease.

Characterization of progressive metaplasia in the gastric corpus mucosa of Mongolian gerbils infected with Helicobacter pylori.

Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia are considered neoplastic precursors of gastric adenocarcinoma in humans. Loss of parietal cells causes the development of SPEM in the gastric corpus and then chronic inflammation drives SPEM toward a more proliferative lineage. Mongolian gerbils infected with Helicobacter pylori develop chronic gastritis and metaplasia, mimicking aspects of human gastritis with H.

Helicobacter pylori and CagA under conditions of iron deficiency.

Iron deficiency is the most common nutritional deficiency worldwide and compelling evidence has demonstrated that this condition heightens the risk of gastric cancer. Infection with Helicobacter pylori is the strongest known risk factor for the development of gastric adenocarcinoma. Recent work has demonstrated that, under conditions of iron deficiency, H.

Micronutrients: A double-edged sword in microbial-induced gastric carcinogenesis.

Epidemiologic studies throughout the world have uniformly demonstrated significant relationships between the intake of dietary micronutrients and gastric cancer risk. An exciting concept that has gained considerable traction recently is that micronutrients modulate gene expression within , the strongest identified risk factor for gastric carcinogenesis. We present evidence here that essential micronutrients have a direct effect on virulence, which subsequently affects interactions at the host-pathogen interface, thereby facilitating the development of premalignant and malignant lesions in the stomach.

Identification of alanyl aminopeptidase (CD13) as a surface marker for isolation of mature gastric zymogenic chief cells.

Injury and inflammation in the gastric epithelium can cause disruption of the pathways that guide the differentiation of cell lineages, which in turn can cause persistent alterations in differentiation patterns, known as metaplasia. Metaplasia that occurs in the stomach is associated with increased risk for cancer. Methods for isolating distinct gastric epithelial cell populations would facilitate dissection of the molecular and cellular pathways that guide normal and metaplastic differentiation.

Micronutrients: A Double-Edged Sword in Microbe-Induced Gastric Carcinogenesis.

Epidemiologic studies throughout the world have uniformly demonstrated significant relationships between the intake of dietary micronutrients and gastric cancer risk. An exciting concept that has recently gained considerable traction is that micronutrients modulate gene expression within Helicobacter pylori, the strongest identified risk factor for gastric carcinogenesis. We present evidence here that essential micronutrients have a direct effect on H.

Microbial Regulation of p53 Tumor Suppressor.

p53 tumor suppressor has been identified as a protein interacting with the large T antigen produced by simian vacuolating virus 40 (SV40). Subsequent research on p53 inhibition by SV40 and other tumor viruses has not only helped to gain a better understanding of viral biology, but also shaped our knowledge of human tumorigenesis. Recent studies have found, however, that inhibition of p53 is not strictly in the realm of viruses.

Helicobacter pylori bacteria alter the p53 stress response via ERK-HDM2 pathway.

H. pylori infection is the strongest known risk factor for gastric cancer. Inhibition of host tumor suppressor mechanisms by the bacteria underlies the development of this disease.

Regulation of Helicobacter pylori Virulence Within the Context of Iron Deficiency.

Helicobacter pylori strains that harbor the oncoprotein CagA increase gastric cancer risk, and this risk is augmented under iron-deficient conditions. We demonstrate here that iron depletion induces coccoid morphology in strains lacking cagA. To evaluate the stability of augmented H.

Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells.

Objective: Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag(+) strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H.