The mutual interactions among Helicobacter pylori, chronic gastritis, and the gut microbiota: a population-based study in Jinjiang, Fujian

Abstract

Objectives: Helicobacter pylori (H. pylori) is a type of bacteria that infects the stomach lining, and it is a major cause of chronic gastritis (CG). H. pylori infection can influence the composition of the gastric microbiota. Additionally, alterations in the gut microbiome have been associated with various health conditions, including gastrointestinal disorders. The dysbiosis in gut microbiota of human is associated with the decreased secretion of gastric acid. Chronic atrophic gastritis (CAG) and H. pylori infection are also causes of reduced gastric acid secretion. However, the specific details of how H. pylori infection and CG, especially for CAG, influence the gut microbiome can vary and are still an area of ongoing investigation. The incidence of CAG and infection rate of H. pylori has obvious regional characteristics, and Fujian Province in China is a high incidence area of CAG as well as H. pylori infection. We aimed to characterize the microbial changes and find potential diagnostic markers associated with infection of H. pylori as well as CG of subjects in Jinjiang City, Fujian Province, China.

Participants: Enrollment involved sequencing the 16S rRNA gene in fecal samples from 176 cases, adhering to stringent inclusion and exclusion criteria. For our study, we included healthy volunteers (Normal), individuals with chronic non-atrophic gastritis (CNAG), and those with CAG from Fujian, China. The aim was to assess gut microbiome dysbiosis based on various histopathological features. QIIME and LEfSe analyses were performed. There were 176 cases, comprising 126 individuals who tested negative for H. pylori and 50 who tested positive defined by C14 urea breath tests and histopathological findings in biopsies obtained through endoscopy. CAG was also staged by applying OLGIM system.

Results: When merging the outcomes from 16S rRNA gene sequencing results, there were no notable variations in alpha diversity among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and H. pylori positive [Hp (+)] and H. pylori negative [Hp (-)] groups. Beta diversity among different groups show significant separation through the NMDS diagrams. LEfSe analyses confirmed 2, 3, and 6 bacterial species were in abundance in the Normal, CNAG, and CAG groups; 26 and 2 species in the OLGIM I and OLGIM II group; 22 significant phylotypes were identified in Hp (+) and Hp (-) group, 21 and 1, respectively; 9 bacterial species exhibited significant differences between individuals with CG who were Hp (+) and those who were Hp (-).

Conclusion: The study uncovered notable distinctions in the characteristics of gut microbiota among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and Hp (+) and Hp (-) groups. Through the analysis of H. pylori infection in CNAG and CAG groups, we found the gut microbiota characteristics of different group show significant difference because of H. pylori infection. Several bacterial genera could potentially serve as diagnostic markers for H. pylori infection and the progression of CG.

Keywords: Helicobacter pylori; chronic atrophic gastritis; gastric microenvironment; gastritis; gut microbiota.

Figure 1

Flowchart of time and population included in the study.

Figure 2

Venn map. (A) The Venn map of the OTUs distribution of group Normal, CNAG, and CAG. (B) The Venn map of the OTUs distribution of group OLGIM I and OLGIM II. (C) The Venn map of the OTUs distribution of group H. pylori positive and H. pylori negative.

Figure 3

The heatmap of the top 30 genera in group Normal, CNAG, and CAG.

Figure 4

The heatmap of the top 60 genera for all the chronic gastritis subjects.

Figure 5

The predominant bacterial phylum distribution composition of each group. (A) The predominant bacterial phyla in group Normal, CNAG, and CAG. (B) The predominant bacterial phyla in group OLGIM I and OLGIM II. (C) The predominant bacterial phyla in group H. pylori positive and H. pylori negative.

Figure 6

Characteristics of the gut microbiota alpha diversity among each group. (A) Characteristics of the gut microbiota alpha diversity among group Normal, CNAG, and CAG. (B) Characteristics of the gut microbiota alpha diversity between group OLGIM I and OLGIM II. (C) Characteristics of the gut microbiota alpha diversity between group H. pylori positive and H. pylori negative.

Figure 7

Comparison of the microbiota beta diversity among each group. (A) The microbiota beta diversity of group Normal, CNAG, and CAG. (B) The microbiota beta diversity of group OLGIM I and OLGIM II. (C) The microbiota beta diversity of group H. pylori positive and H. pylori negative.

Figure 8

Comparing the distributions of the gut microbiota composition among each group. (A) Histogram of LDA value distribution represents the magnitude of the impact of different species among group Normal, CNAG, and CAG. (B) Histogram of LDA value distribution represents the magnitude of the impact of different species among group OLGIM I and OLGIM II. (C) Histogram of LDA value distribution represents the magnitude of the impact of different species among group H. pylori positive and H. pylori negative.

Figure 9

Comparison of the significantly enriched genera in each group. (A) The histogram of LDA values represents the impact level of significantly enriched genera in the Normal, CAG, OLGIM I, and Hp (-) group. (B) Histogram of LDA value distribution represents the impact level of significantly enriched genera in the CNAG-Hp (-) and CAG-Hp (-) group.

Figure 10

Comparing the distributions of the gut microbiota structure among each group. (A) The cladogram illustrates the phylogenetic distribution of microbial lineages between group H. pylori positive and H. pylori negative among CNAG subjects. (B) The cladogram illustrates the phylogenetic distribution of microbial lineages between group H. pylori positive and H. pylori negative among CAG subjects.