| Autor: |
Shen Z; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Dzink-Fox J; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Feng Y; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Muthupalani S; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Mannion AJ; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Sheh A; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Whary MT; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Holcombe HR; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA., Piazuelo BM; Division of Gastroenterology, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA., Bravo LE; Department of Pathology, Universidad del Valle, Cali, Colombia., Josenhans C; Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer-Institute, Ludwig Maximilians University, Munich, Germany., Suerbaum S; Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer-Institute, Ludwig Maximilians University, Munich, Germany., Wilson KT; Division of Gastroenterology, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA., Peek RM; Division of Gastroenterology, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA., Wang TC; Division of Gastroenterology and Irvine Cancer Research Center, Columbia Universitygrid.21729.3f, New York, New York, USA., Fox JG; Division of Comparative Medicine, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA. |
| Abstrakt: |
In populations with similar prevalence of Helicobacter pylori infection, cancer risk can vary dramatically. Changes in composition or structure of bacterial communities in the stomach, either at the time of exposure or over the course of H. pylori infection, may contribute to gastric pathology. In this study, a population of 37 patients from the low-gastric-cancer-risk (LGCR) region of Tumaco, Colombia, and the high-gastric-cancer-risk (HGCR) region of Túquerres, Colombia, were recruited for gastric endoscopy. Antral biopsy specimens were processed for histology and bacterial isolation. Fifty-nine distinct species among 26 genera were isolated by aerobic, anaerobic, and microaerobic culture and confirmed by 16S rRNA analysis. Urease-positive Staphylococcus epidermidis and Streptococcus salivarius were frequently isolated from gastric biopsy specimens. We asked whether coinfection of H. pylori with urease-positive S. salivarius and/or S. epidermidis had a demonstrable effect on H. pylori - induced gastritis in the germfree (GF) INS-GAS mouse model. Coinfections with S. salivarius and/or S. epidermidis did not affect gastric H. pylori colonization. At 5 months postinfection, GF INS-GAS mice coinfected with H. pylori and S. salivarius had statistically higher pathological scores in the stomachs than mice infected with H. pylori only or H. pylori with S. epidermidis ( P < 0.05). S. epidermidis coinfection with H. pylori did not significantly change stomach pathology, but levels of the proinflammatory cytokine genes Il-1β , Il-17A , and Il-22 were significantly lower than in H. pylori-monoinfected mice. This study demonstrates that non-H. pylori urease-positive bacteria may play a role in the severity of H. pylori - induced gastric cancer in humans. IMPORTANCE Chronic infection with H. pylori is the main cause of gastric cancer, which is a global health problem. In two Colombian populations with high levels of H. pylori prevalence, the regional gastric cancer rates are considerably different. Host genetic background, H. pylori biotype, environmental toxins, and dietary choices are among the known risk factors for stomach cancer. The potential role of non-H. pylori gastric microbiota in gastric carcinogenesis is being increasingly recognized. In this study, we isolated 59 bacterial species from 37 stomach biopsy samples of Colombian patients from both low-gastric-cancer-risk and high-gastric-cancer-risk regions. Urease-positive S. epidermidis and S. salivarius commonly cultured from the stomachs, along with H. pylori, were inoculated into germfree INS-GAS mice. S. salivarius coinfection with H. pylori induced significantly higher gastric pathology than in H. pylori-monoinfected mice, whereas S. epidermidis coinfection caused significantly lower H. pylori-induced proinflammatory cytokine responses than in H. pylori-monoinfected mice. This study reinforces the argument that the non-H. pylori stomach microflora play a role in the severity of H. pylori-induced gastric cancer. |
