Low Bifidobacterium Abundance in the Lower Gut Microbiota Is Associated With Helicobacter pylori-Related Gastric Ulcer and Gastric Cancer

Abstract

Helicobacter pylori infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most H. pylori-infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the H. pylori-associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to H. pylori infection and related gastric diseases. Here, we studied H. pylori infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents (N = 375) in southwestern India by standard H. pylori culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent H. pylori strains (vacAs1i1m1cagA+) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the H. pylori-infected vs. H. pylori-non-infected individuals. Bifidobacterium (belonging to the phylum Actinobacteria) and Bacteroides (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the H. pylori+ group than the H. pylori- group (p < 0.05). On the contrary, for the H. pylori+ group, genus Dialister (bacteria belonging to the phylum Firmicutes) and genus Prevotella (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the H. pylori- group (p < 0.05). Notably, those who carried H. pylori in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance (p < 0.05) of several Bifidobacterium species (e.g., B. adolescentis, B. longum) in the lower gut suggesting a protective role of Bifidobacterium. Our results show the link between lower gastrointestinal microbes and upper gastrointestinal diseases. Moreover, the results are important for developing effective probiotic and early prognosis of severe gastric diseases.

Vaginal microbiome is associated with endometrial cancer grade and histology

“…Bifidobacterium longum was the most greatly suppressed species in terms of abundance in HG vs LG disease. B. longum has been shown to have low relative abundance in patients with the most aggressive forms of gastric cancer, suggesting it may be protective (25). It has also been shown to improve immune-mediated tumor control (26).…”

Helicobacter pylori in Human Stomach: The Inconsistencies in Clinical Outcomes and the Probable Causes

“…In Indian population, for the H. pylori infected individuals, the relative abundance of genus Prevotella and genus Dialister were found to be higher, while the relative abundance of the genus Bifidobacterium and genus Bacteroidetes were found to be lower in the intestine (Devi et al, 2021). Most remarkably, the H. pylori infected patients who had developed either gastric ulcer or gastric cancer, had a significantly low relative abundance of several species of Bifidobacterium (e.g., B. Longum and B. adolescentis) in the intestine (Table 4; Figure 1; Devi et al, 2021). It is worth mentioning that the bacteria belong to genus Bifidobacterium are mostly intestinal commensal bacterium and some of them carry anti-H. pylori, anti-cancer, and anti-ulcer activities.…”

“…In the Chinese population, a decrease in the abundance of Bacteroidetes and an increase in the abundance of Firmicutes and Proteobacteria were observed in the intestine of the H. pylori infected individuals (Gao et al, 2018). In Indian population, for the H. pylori infected individuals, the relative abundance of genus Prevotella and genus Dialister were found to be higher, while the relative abundance of the genus Bifidobacterium and genus Bacteroidetes were found to be lower in the intestine (Devi et al, 2021). Most remarkably, the H. pylori infected patients who had developed either gastric ulcer or gastric cancer, had a significantly low relative abundance of several species of Bifidobacterium (e.g., B. Longum and B. adolescentis) in the intestine (Table 4; Figure 1; Devi et al, 2021).…”

“…Mutations in the gene encoding E-cadherin leads to increased cell proliferation, migration, and reduced FIGURE 2 | The predominant vacA genotypes and cagA status in different regions of the world. East Asia, North America, South America, Europe (France, Italy, Portugal Spain, Northern, and Eastern Europe), Africa (Nigeria and South Africa), India (West Bengal and Kerala), and Australia (van Doorn et al, 1999a;Mukhopadhyay et al, 2000;Chattopadhyay et al, 2002;Idowu et al, 2019;Ofori et al, 2019;Devi et al, 2021). The predominant vacA genotypes vary between and within the continents.…”

“…In murine model, it has been shown that H. pylori colonization in stomach is capable of altering the intestinal microbiota (Kienesberger et al, 2016). In human, for the Chinese and Indian populations, H. pylori infection in stomach leads to an increase in the microbial diversity in the intestine (Figure 1; Gao et al, 2018;Devi et al, 2021). This increased diversity in the intestinal microbiota for the H. pylori infected individuals could be due to the increased pH of the stomach or could be due to the altered gut immunity.…”