Role of Indigenous Lactobacilli in Gastrin-Mediated Acid Production in the Mouse Stomach

Abstract

It is known that the stomach is colonized by indigenous lactobacilli in mice. The aim of this study was to examine the role of such lactobacilli in the development of the stomach. For a DNA microarray analysis, germ-free BALB/c mice were orally inoculated with 10 9 CFU lactobacilli, and their stomachs were excised after 10 days to extract RNA. As a result, lactobacillus-associated gnotobiotic mice showed dramatically decreased expression of the gastrin gene in comparison to germ-free mice. The mean of the log 2 fold change in the gastrin gene was ؊4.3. Immunohistochemistry also demonstrated the number of gastrin-positive (gastrin ؉ ) cells to be significantly lower in the lactobacillus-associated gnotobiotic mice than in the germ-free mice. However, there was no significant difference in the number of somatostatin ؉ cells in these groups of mice. Consequently, gastric acid secretion also decreased in the mice colonized by lactobacilli. In addition, an increase in the expression of the genes related to muscle system development, such as nebulin and troponin genes, was observed in lactobacillus-associated mice. Moreover, infection of germ-free mice with Helicobacter pylori also showed the down-and upregulation of gastrin and muscle genes, respectively, in the stomach. These results thus suggested that indigenous lactobacilli in the stomach significantly affect the regulation of gastrinmediated gastric acid secretion without affecting somatostatin secretion in mice, while H. pylori also exerts such an effect on the stomach.The human stomach contains only a few species of bacteria if it is free from infection with Helicobacter pylori (3). During fasting, gastric juice contains only small numbers of bacteria, approximately 10 2 to 10 3 /ml, which include Streptococcus, Lactobacillus, and Veillonella. However, these bacteria are considered nonresidents that are only in transit from the oral cavity and throat (13,19). The scarcity of such bacteria in the human stomach appears to be due to the high acidity of the luminal medium.While H. pylori is a well-known pathogenic bacterium that causes peptic ulcers and cancer in the human stomach, the bacterium has also been proposed to belong to the indigenous gastric microbiota of humans from the earliest times (2). That hypothesis is supported by the fact that H. pylori is acquired in early childhood and thereafter remains stably colonizing the stomach for decades in substantial numbers. This raises questions about the role of H. pylori as the indigenous bacteria of the stomach in the physiological development and function of the organ. However, it is difficult to clarify the answers to this question by an infection study using H. pylori, because various pathogenic factors of H. pylori, such as CagA, vacuolating toxins, and urease and its metabolites, induce chronic pathological inflammation in the gastric tissue, which obscures the physiological role of H. pylori as an indigenous bacterium.In a previous study (12), we found an indigenous microbiota that predominantly consists...

The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

“…[117][118][119] Lactobacilli are prevalent in gerbil stomachs like the mouse, due to their colonization of the non-glandular forestomach. 108 Three studies examined the effects of short, 8-12 wk H. pylori infections on the gastric microbiota, and observed few changes in the gastric phyla but documented changes in less abundant gastric genera. 78,118,119 In gerbils with H. pylori infection, two groups saw decreases in lactobacilli, but both had small numbers and depended on culture for identification.…”

“…72,77 However, it has been noted that the squamous epithelium is the primary site of colonization of lactobacilli. 108 Further standardization of methodologies is required to compare equivalent data.…”

Survival in hostile territory: the microbiota of the stomach

“…The low intragastric pH, which has been demonstrated to be very important for the inactivation of ingested microorganisms (Sun et al, 2003a;Friis-Hansen et al, 2006;Tennant et al, 2008), differs considerably between different species (reviewed in Kararli, 1995). Mice possess a relatively high intragastric pH (pH 3-4; Scarff et al, 1999;Icatlo et al, 2000;Aebischer et al, 2006;McConnell et al, 2008;Takahashi et al, 2011), which decreases the potential to inactivate microorganisms, thereby facilitating the gastric growth of different bacteria. In contrast, other species including Mongolian gerbils (Mollenhauer-Rektorschek et al, 2002) and guinea pigs (Schreiber & Scheid, 1997) have low intragastric pH values (pH < 2), which are similar to those measured in humans (Teyssen et al, 1995;Vakevainen et al, 2000).…”

Gastric secretion

“…In a gastric carcinoma cell line, the proinflammatory cytokine interleukin1b, which is induced during H. pylori infection, repressed gastrin expression by activating Smad 7 with subsequent inhibition of nuclear localization of the Smad 3/4 complex [9]. Germ-free BALB/c mice inoculated with lactobacilli showed decreased expression of the gastrin gene, decreased number of G cells, and decreased gastric acid secretion compared to germ-free mice [10].…”