Microbiota in the stomach and application of probiotics to gastroduodenal diseases

Abstract

The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for Helicobacter pylori (H. pylori) infection significantly improves gastric mucosal inflammation and decreases the density of H. pylori on the mucosa, although complete eradication of H. pylori has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the H. pylori eradication rate, especially when the H. pylori strains are resistant to antimicrobial agents. While H. pylori has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than H. pylori are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of H. pylori. Increased non-H. pylori Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after H. pylori eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.

Keywords: Functional dyspepsia; Helicobacter pylori; Microbiota; Post-eradication gastric cancers; Probiotics; Stomach.

Figure 1

Comparison of the microbiota in the saliva, gastric fluid and feces, and the influence of proton-pump inhibitors. Bacterial compositions at the genus level in saliva (top), gastric fluid (median) and feces (bottom) are shown. The average of read numbers of the top 10 major genera are indicated in each group. Open and filled bars represent proton-pump inhibitor (PPI)-nonusers and PPI-users, respectively. Asterisks show a significant difference according to Student t-test. ^aP < 0.05. PPI: Proton-pump inhibitor. Citation: Tsuda A, Suda W, Morita H, Takanashi K, Takagi A, Koga Y, Hattori M. Influence of Proton-Pump Inhibitors on the Luminal Microbiota in the Gastrointestinal Tract. Clin Transl Gastroenterol 2015; 6: e89. Copyright ©Wolters Kluwer Health, Inc. 2015. Published by Wolters Kluwer Health, Inc.

Figure 2

Observation of Helicobacter pylori by scanning electron microscopy. The bar at the bottom shows 1 μm.

Figure 3

Correlation between pH and lipopolysaccharide activity in gastric fluid. The pH values and lipopolysaccharide activity of gastric fluid samples from 136 subjects were examined using a recombinant factor C assay kit. The correlation coefficients of the both parameters by Spearman test (r) is shown on the upper left. LPS: Lipopolysaccharide. Citation: Sano M, Uchida T, Igarashi M, Matsuoka T, Kimura M, Koike J, Fujisawa M, Mizukami H, Monma M, Teramura E, Yoshihara S, Sato H, Morimachi M, Ito A, Ueda T, Shiraishi K, Matsushima M, Suzuki T, Koga Y. Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach With Low Acidity. Clin Transl Gastroenterol 2020; 11: e00190. Copyright ©Wolters Kluwer Health, Inc. 2020. Published by Wolters Kluwer Health, Inc.

Figure 4

Effect of LG21 administration on the pH and lipopolysaccharide activity in the gastric fluid. Ten subjects who had gastric fluid (GF) with low acidity and high lipopolysaccharide (LPS) activity consumed yogurt containing 10⁹ CFU of LG21 every day for 3 mo. The pH value and LPS activity in the GF were measured before and after LG21 treatment. LPS: Lipopolysaccharide.

Figure 5

Pathophysiology of functional dyspepsia and possible mechanisms of the effects of LG21 treatment. SIBO: Small intestinal bacterial overgrowth; LPS: Lipopolysaccharide.