The Degree of Helicobacter pylori-Triggered Inflammation Is Manipulated by Preinfection Host Microbiota

Abstract

bHelicobacter pylori infects over 3 billion people worldwide and is the primary risk factor for gastric cancer. Most individuals infected with H. pylori develop only asymptomatic gastritis; however, some develop ulcers or gastric adenocarcinoma. We demonstrate that one previously unappreciated parameter influencing H. pylori disease outcome is variation in the preinfection host microbiota. Utilizing a mouse model, we altered the microbiota by antibiotic treatment and found that these alterations resulted in significantly lowered H. pylori-triggered inflammation. Specifically, antibiotic pretreatment reduced CD4 ؉ T-helper cells and Ifn␥ transcript levels in gastric tissue after H. pylori infection. The bacterial communities in mice with a reduced response to H. pylori displayed many differences from those in untreated mice, including significantly more cluster IV and XIVa Clostridium spp., bacteria known to influence inflammation via regulatory T cell populations. Our findings suggest that microbiota composition, perhaps Clostridium spp., contributes to the variable disease outcome of H. pylori infection by altering the recruitment of CD4 ؉ T cells to the gastric compartment. Our results suggest that gastric microbiota could be used as a diagnostic tool to determine which patients are at risk for developing severe disease.

The gastric microbial community,Helicobacter pyloricolonization, and disease

“…A single strain of mouse purchased from different laboratories can have profoundly different microbiota and immune profiles in the lower GI tract, 41 yet carry similar levels of H. pylori in the stomach. 19 We have made similar observations (Fig. 3).…”

“…For example, antibiotic treatment prior to H. pylori infection led to a reduction in overall gastric inflammation and CD4+ T-cell recruitment compared with untreated mice. 19 This phenotype coincided with altered membership in the gastric community, although it is not clear if the differences in pathology were due to changes in the gastric or non-gastric microbial communities. Modulation of H. pylori pathogenesis has also been observed in mice co-infected with non-pylori Helicobacter spp.…”

“…In wild type mice, culture-independent studies found that neither long nor short-term H. pylori infection had a substantial impact on the gastric microbiota. 18,19 Studies in hypergastrinemic INS-GAS mice demonstrated that H. pylori infection caused a reduction in Bacteroidetes and an increase in Firmicutes. 20 When these mice were gnotobiotically colonized with members of the altered Schaedler's flora (ASF), H. pylori infection was accompanied by decreased Bacteroides, and both a decrease (Clostridium) and increase (Lactobacillus) in Firmicutes.…”

Immunohistopathological Role of Bcl2 and P53 Gene Expression in Helicobacter Pylori Cytotoxin-Associated Gene a Positive Versus Cytotoxin-Associated Gene a Negative Antral Predominant Non-Atrophic Gastritis in Iraqi Patients

“…In this study, chronic inflammation intensity expressed by moderate to heavy lymphocytes and PMNs intensity within the lamina propria were observed which come in agreement with others [32][33][34][35], significant difference in inflammation activity grades and in inflammation intensity grades between CagA positive versus CagA negative APNG patients were detected. Significant correlations were detected between HP CagA, inflammation activity grades, and inflammation intensity grades that come in line with others stated that significant correlation was found between HP density and the grade of acute and chronic inflammation [36,37].…”

Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients

“…3 and 4A), although differences in the gastric mucosa communities between the two patient groups could be explained by relative abundance differences of at least 15 specific biomarkers ( (49) and that drug-induced variations in specific microbiota members affect the immune response to H. pylori, thereby contributing to H. pylori-associated upper gastrointestinal diseases (50). The acidity of the human stomach can be greatly compromised in the case of H. pylori infection (and H. pylori-associated atrophic gastritis) and also in the case of pharmacological interventions, for example, with PPIs (6).…”