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 gastrin-mediated gastric acid secretion without affecting somatostatin secretion in mice, while H. pylori also exerts such an effect on the stomach.

Fig. 1.

Immunohistochemistry of the stomach for gastrin. The stomachs of GF (A and C) and LJ88AG (B and D) mice were excised 10 days after inoculation, and the antrum regions were stained for gastrin (green fluorescence) (A and B) or somatostatin (red fluorescence) together with gastrin (C and D). Nuclei (blue) were stained with DAPI. Bars, 50 μm.

Fig. 2.

Histology of the stomach. The stomachs of GF mice (A, B, and C) and gnotobiotic mice associated with LG21 at birth (+LG21; D, E, and F) were excised at 8 weeks of age and then stained with hematoxylin and eosin for histological analysis. Panels A and D, B and E, and C and F show the corpus, the antrum, and the muscle layer of the stomach, respectively. Bars, 200 μm. Magnification, ×400 (C and F).