Effect of Helicobacter pylori-related chronic gastritis on gastrointestinal microorganisms and brain neurotransmitters in mice

Abstract

The effects of Helicobacter pylori (Hp)-related chronic gastritis on gastrointestinal microorganisms or brain neurotransmitters are not fully understood. Here, this study selected SPF C57BL/6 mice to set up a Hp-related chronic gastritis experiment group and a blank control group, and used omics to explore the specific effects of Hp-related chronic gastritis on gastrointestinal microorganisms and brain neurotransmitters in mice. The Tyramine (TyrA) content in the female experiment group's brain was considerably reduced compared to the female control group (p < 0.01), and TyrA was strongly correlated with 13 gastrointestinal microorganisms with significant differences, such as Acinetobacter_baumannii (p < 0.05). The His content in the male experiment group's brain was significantly higher than that in the male control group (p < 0.05), and His was strongly correlated with four gastrointestinal microorganisms with significant differences, such as Acinetobacter_baumannii (p < 0.05). The Levodopa (DOPA) content in the female control group's brain was significantly lower than that in the male control group (p < 0.05), and DOPA was strongly correlated with 19 gastrointestinal microorganisms with significant differences, such as Achromobacter_xylosoxidans (p < 0.05). The contents of L-Glutamine (Gln), L-Glutamine (GABA), Noradrenaline hydrochloride (NE), and Adrenaline hydrochloride (E) in the female experiment group's brain were significantly lower than those in the male experiment group (p < 0.05), and Gln, GABA, NE, and E were strongly correlated with 41, 28, 40, and 33 gastrointestinal microorganisms with significant differences (p < 0.05), respectively. These results indicate that Hp-related chronic gastritis could affect gastrointestinal microorganisms and brain neurotransmitters in mice with certain gender differences, and the changes in brain neurotransmitters might be related to the changes in gastrointestinal microorganisms.

Keywords: Hp-related chronic gastritis; metabolomics; metagenomics; microorganism; neurotransmitter.

FIGURE 1

General condition. (A) Changes in body weight. (B) Results of gastric mucosal urease test to detect Hp in the experiment group. (C) Map of gastric mucosa stained with HE in the control group. (D) Map of gastric mucosa stained with HE in the experiment group.

FIGURE 2

Difference analysis of gastrointestinal microorganisms between the experiment and control groups. (A) Wayne map of common and endemic species. (B) LDA histogram of LEfSe analysis. C denotes class, o denotes order, f denotes family, g denotes genus, and s denotes species. In the experiment group, 8 cecal colon contents were obtained from male mice and 8 cecal colon contents from female mice. In the control group, 7 cecal colon contents were obtained from male mice and 7 cecal colon contents from female mice, because the sample sizes of one male and one female mouse in the control group was too little to be subjected to metagenomic detection.

FIGURE 3

Difference analysis of gastrointestinal microorganisms between the same gender in the experiment and control groups. (A) Wayne map of common and endemic species of gastrointestinal microorganisms of female mice in the experiment and control groups. (B) LDA histogram of gastrointestinal microbial LEfSe analysis of female mice in the experiment and control groups. (C) Wayne map of common and endemic species of gastrointestinal microorganisms of male mice in the experiment and control groups. (D) LDA histogram of gastrointestinal microbial LEfSe analysis of male mice in the experiment and control groups. K denotes kingdom, p denotes phylum, c denotes class, o denotes order, f denotes family, g denotes genus, and s denotes species. In the experiment group, 8 cecal colon contents were obtained from male mice and 8 cecal colon contents from female mice. In the control group, 7 cecal colon contents were obtained from male mice and 7 cecal colon contents from female mice.

FIGURE 4

Difference analysis of gastrointestinal microorganisms between different genders in the experiment and control groups. (A) Wayne map of common and endemic species of gastrointestinal microorganisms of male and female mice in the control group. (B) LDA histogram of gastrointestinal microbial LEfSe analysis of male and female mice in the control group. (C) Wayne map of common and endemic species of gastrointestinal microorganisms of male and female mice in the experiment group. (D) LDA histogram of gastrointestinal microbial LEfSe analysis of female and male mice in the experiment group. p denotes phylum, c denotes class, o denotes order, f denotes family, g denotes genus, and s denotes species. In the experiment group, 8 cecal colon contents were obtained from male mice and 8 cecal colon contents from female mice. In the control group, 7 cecal colon contents were obtained from male mice and 7 cecal colon contents from female mice.

FIGURE 5

Difference analysis of brain neurotransmitters between the experiment and control groups. (A) OPLSDA point cloud diagram. It indicated the overall distribution of the samples. (B) Random forest diagram. The horizontal axis of the left panel measured the importance of a metabolite in the random forest, and the right panel was a heat map of the content of 15 metabolites in the two groups. (C) OPLSDA metabolite importance diagram. Metabolites with their names marked in yellow were brain neurotransmitters with corrected p < 0.05 and VIP >1, which were significantly different between groups. (D) Box diagram of brain neurotransmitter TyrA (** denotes p < 0.01). It displayed the differences between groups visually. The experiment and control groups obtained 8 brain tissue samples from male mice and 8 brain tissue samples from female mice, respectively.

FIGURE 6

Difference analysis of brain neurotransmitters between the same gender in the experiment and control groups. (A) OPLSDA point cloud diagram of brain neurotransmitters of female mice in the experiment and control groups. (B) Random forest diagram of brain neurotransmitters of female mice in the experiment and control groups. (C) OPLSDA metabolite importance diagram of brain neurotransmitters of female mice in experiment and control groups. (D) Box diagram of brain neurotransmitter TyrA of female mice in the experiment and control groups (** indicates p < 0.01). (E) OPLSDA point cloud diagram of brain neurotransmitters of male mice in experiment and control groups. (F) Random forest diagram of brain neurotransmitters of male mice in experiment and control groups. (G) OPLSDA metabolite importance diagram of brain neurotransmitters of male mice in experiment and control groups. (H) Box diagram of brain neurotransmitter His of male mice in the experiment and control groups (* represents p < 0.05). The experiment and control groups obtained 8 brain tissue samples from male mice and 8 brain tissue samples from female mice, respectively.

FIGURE 7

Difference analysis of brain neurotransmitters between different genders in the experiment and control groups. (A) OPLSDA point cloud diagram of brain neurotransmitters of male and female mice in the control group. (B) Random forest diagram of brain neurotransmitters of male and female mice in the control group. (C) OPLSDA metabolite importance diagram of brain neurotransmitters of male and female mice in the control group. (D) Box diagram of brain neurotransmitter DOPA of male and female mice in the control group (* represents p < 0.05). (E) OPLSDA point cloud diagram of brain neurotransmitters of male and female mice in experiment group. (F) Random forest diagram of gastrointestinal microorganisms of male and female mice in the experiment group. (G) OPLSDA metabolite importance diagram of brain neurotransmitters of male and female mice in the experiment group. (H) Box diagram of brain neurotransmitter Gln, NE, GABA, and E of male and female mice in the experiment group (* represents p < 0.05, ** indicates p < 0.01). The experiment and control groups obtained 8 brain tissue samples from male mice and 8 brain tissue samples from female mice, respectively.

FIGURE 8

Heat map of the association between brain neurotransmitters and gastrointestinal microorganisms with significant differences. (A) Heat map of the association in the experiment and control groups. (B) Heat map of the association in the female experiment and control groups. (C) Heat map of the association in the male experiment and control groups. (D) Heat map of the association in the male and female control groups. (E) Heat map of the association in the male and female experiment groups.