Association Between Gut Microbiota and Helicobacter pylori-Related Gastric Lesions in a High-Risk Population of Gastric Cancer

Juan-Juan Gao, Yang Zhang, Markus Gerhard, Raquel Mejias-Luque, Lian Zhang, Michael Vieth, Jun-Ling Ma, Monther Bajbouj, Stepan Suchanek, Wei-Dong Liu, Kurt Ulm, Michael Quante, Zhe-Xuan Li, Tong Zhou, Roland Schmid, Meinhard Classen, Wen-Qing Li, Wei-Cheng You, Kai-Feng Pan, Juan-Juan Gao, Yang Zhang, Markus Gerhard, Raquel Mejias-Luque, Lian Zhang, Michael Vieth, Jun-Ling Ma, Monther Bajbouj, Stepan Suchanek, Wei-Dong Liu, Kurt Ulm, Michael Quante, Zhe-Xuan Li, Tong Zhou, Roland Schmid, Meinhard Classen, Wen-Qing Li, Wei-Cheng You, Kai-Feng Pan

Abstract

Eradication of Helicobacter pylori has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and H. pylori-related gastric lesions in 47 subjects by deep sequencing of microbial 16S ribosomal RNA (rRNA) gene in fecal samples. The dominant phyla in fecal samples were Bacteroidetes, Firmicutes, and Proteobacteria with average relative abundances of 54.77, 31.37 and 12.91%, respectively. Microbial diversity analysis showed that observed species and Shannon index were increased in subjects with past or current H. pylori infection compared with negative subjects. As for the differential bacteria, the average relative abundance of Bacteroidetes was found to significantly decrease from H. pylori negative (66.16%) to past infection group (33.01%, p = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, p = 0.027). For Firmicutes and Proteobacteria, the average relative abundances showed elevated trends in the past H. pylori infection group (47.11, 20.53%) compared to negative group (23.44, 9.05%, p = 0.068 and 0.246, respectively), and similar increased trends were also found from normal (18.23, 5.05%) to gastritis (35.31, 7.23%, p = 0.016 and 0.294, respectively) or metaplasia subjects (32.33, 20.07%, both p < 0.05). These findings suggest that the alterations of fecal microbiota, especially the dominant phyla of Bacteroidetes, Firmicutes and Proteobacteria, may be involved in the process of H. pylori-related gastric lesion progression and provide hints for future evaluation of microbial changes after H. pylori eradication.

Keywords: 16S ribosomal RNA gene sequencing; Helicobacter pylori; gastric lesions; gut microbiota; microbial diversity.

Figures

Figure 1
Figure 1
Composition of fecal microbiota. (A) Relative abundance distribution of major phyla (top 10) in 47 fecal samples. Phyla were sorted by decreasing order of average relative abundance. H. pylori status and gastric lesions observed for each subject are listed below. (B) Relative abundance distribution of major genera (top 20) in 47 fecal samples. Genera were sorted by decreasing order of average relative abundance as in (A). H. pylori status: N, H. pylori negative; P, past H. pylori infection; C, current H. pylori infection. Gastric lesions: N, normal; G, gastritis; M, metaplasia.
Figure 2
Figure 2
Associations between Helicobacter pylori infection and fecal microbiota. (A) Boxplot of observed species in different H. pylori status groups. The boxes indicate interquartile ranges (IQRs) and the median (blank line).Whiskers extend to the most extreme points within 1.5-fold IQR. Outliers are plotted individually (°). (B) Shannon index in different H. pylori status groups. (C) Heat-map of relative abundance distributions of the phyla in past H. pylori infection (n = 8) and negative groups (n = 15). (D) Cladogram of differently distributed taxa between groups. The differential taxa are illustrated between past H. pylori infection and negative groups, or current H. pylori infection and past infection groups as *p < 0.05 and **p < 0.01, respectively.
Figure 3
Figure 3
Associations of gastric lesions with fecal microbiota. (A) Boxplot of observed species in different gastric lesion groups. (B) Boxplot of Shannon index in different gastric lesion groups. (C) Heat-map demonstrating the relative abundance of different phyla in gastritis (n = 18) and normal (n = 7) samples. (D) Heat-map showing the relative abundance distributions of different phyla in metaplasia (n = 22) and normal samples.
Figure 4
Figure 4
Cladogram of differentially distributed taxa among different gastric lesion groups. The differential taxa are illustrated between gastritis and normal, metaplasia and normal, or metaplasia and gastritis groups as *p < 0.05, **p < 0.01, and ***p < 0.001, respectively.
Figure 5
Figure 5
Relative abundance distributions of specific phyla and genera in different Helicobacter pylori infection status and gastric lesion groups. (A) Boxplot of the main phyla in different H. pylori infection status and gastric lesion groups. (B) Boxplot of specific genera in different H. pylori infection status and gastric lesion groups. Significant differences between groups are indicated as ***p < 0.001, **p < 0.01, and *p < 0.05, respectively.

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