The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

Abstract

The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values<4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota.

Keywords: Helicobacter pylori; bacterial colonization; cancer; gastric; hypochlorhydria; microbiota; stomach.

Figure 1. Diagram depicting anatomy of the stomach and histological representation of the oxyntic glands of the body of the stomach. It is these glands, which include parietal cells, that are lost in gastric atrophy. Reproduced with permission from Fox and Wang 2007.

Figure 2. Taxonomic classification of bacteria. Descriptions of the gastric microbiota focus on the levels of phylum and genus.

Figure 3. Human microbiota composition in multiple sites of the GI tract, including mouth, stomach, duodenum, colon and stool. Note the high variability between individuals and between the antrum and corpus in the stomach. The stomach microbiota also differs significantly from other sites in the GI tract. Reproduced with permission from Stearns et al. 2011.

Figure 4. Illustration depicting anatomy of the mouse stomach. The anatomy of the gerbil stomach is similar. The nonglandular forestomach is the site of dense colonization by lactobacilli, which substantially contribute to the differences in the gastric microbiota of humans and rodents.

Figure 5. Microbiota composition in stomach, cecum, and colon of H pylori-infected male INS-GAS mice (n = 3, 15 weeks postinfection) vs. uninfected controls (n = 2). Note the significant increase in the relative abundance of Firmicutes and decrease of Bacteroidetes in the stomachs of H pylori–infected INS-GAS mice (p < 0.05), whereas no significant changes were observed in the colon and ceca of H. pylori-infected mice. Reproduced with permission from Lofgren et al. 2011.