Gastrointestinal Microbiota Changes in Patients With Gastric Precancerous Lesions

BackgroundGastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets.ResultsAnalysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions.ConclusionsThis study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.

Alterations in Gastric Mucosal Microbiota in Gastric Carcinogenesis: A Systematic Review and Meta-Analysis

Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the alterations in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer (GC).Methods: The systematic review was performed based on a published protocol with the registration number CRD42020206973. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both GC and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD).Results: Our systematic review included 751 GC patients and 792 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer operational taxonomic units (OTUs) (MD = −68.52, 95%CI: −126.65 to −10.39) and a lower Simpson index (MD = −0.13, 95%CI: −0.20 to −0.07) compared with non-cancer group. At the phylum level, gastric cancer group had a higher abundance of Firmicutes (MD = 7.11, 95%CI: 1.76 to 12.46). At the genus level, Streptococcus (MD = 3.03, 95%CI: 0.07 to 6.00) and Lactobacillus (MD = 5.15, 95%CI: 1.27 to 9.04) were found to be enriched in GCgroup. The relative abundance of the rest bacterial phyla or genera analyzed in our study did not significantly differ between two groups. Subgroup analyses indicated that the source of samples was the major source of interstudy heterogeneity.Conclusion: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered.

Interactions between gastric microbiota and metabolites in gastric cancer

The development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.

Influence of Factors Altering Gastric Microbiota on Bariatric Surgery Metabolic Outcomes

The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied.

Gastric Microbiota beyond H. pylori: An Emerging Critical Character in Gastric Carcinogenesis

Gastric cancer (GC) is one of the global leading causes of cancer death. The association between Helicobacter pylori, which is a predominant risk factor for GC, with GC development has been well-studied. Recently, accumulating evidence has demonstrated the presence of a large population of microorganisms other than H. pylori in the human stomach. Existing sequencing studies have revealed microbial compositional and functional alterations in patients with GC and highlighted a progressive shift in the gastric microbiota in gastric carcinogenesis with marked enrichments of oral or intestinal commensals. Moreover, using a combination of gastric bacterial signatures, GC patients could be significantly distinguished from patients with gastritis. These findings, therefore, emphasize the importance of a collective microbial community in gastric carcinogenesis. Here, we provide an overview of non-H. pylori gastric microbes in gastric carcinogenesis. The molecular mechanisms of gastric microbes-related carcinogenesis and potential clinical applications of gastric microbiota as biomarkers of GC are also explored.

Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis—what is currently known?

Currently, gastric cancer is one of the leading death-related cancer globally. The etiopathogenesis of gastric cancer is multifactorial and includes among others dysbiotic alterations of gastric microbiota. Molecular techniques revealed that stomach is not a sterile organ and it is resides with ecosystem of microbes. Due to the fact that the role of Helicobacter pylori infection in development of gastric cancer is established and well-studied, this paper is mainly focused on the role of other bacterial as well as viral and fungal gut microbiota imbalance in gastric carcinogenesis. Notably, not only the composition of gastric microbiota may play an important role in development of gastric cancer, but also its activity. Microbial metabolites, such as short-chain fatty acids, polyamines, N-nitroso compounds, and lactate, may significantly affect gastric carcinogenesis. Therefore, this paper discussed aforementioned aspects with the interdisciplinary insights (regarding also immunological point of view) into the association between gut microbiome and gastric carcinogenesis based on up-to-date studies.

Impact of Helicobacter pylori eradication on the gastric microbiome

Background Helicobacter pylori (Hp) eradication has been used for many years. Yet, the impact of this eradication on the normal gastric microflora is not well understood. In this study, we explored the effect of eradication on the stomach microbial community and its recovery after successful Hp eradication. Methods Among the 89 included patients, 23, 17, 40, and 9 were included in the Hp-negative, Hp-positive, successful eradication, and failed eradication groups, respectively. Four subgroups were further determined according to disease status (Hp-negative chronic gastritis [N-CG], Hp-negative atrophic gastritis [N-AG], successful-eradication chronic gastritis [SE-CG], and atrophic gastritis with successful eradication [SE-AG]). During the endoscopic examination, one piece of gastric mucosa tissue was obtained from the lesser curvature side of the gastric antrum and gastric corpus, respectively. In addition, 16S rDNA gene sequencing was used to analyze the gastric mucosal microbiome. Results In the Hp-negative group, the gastric microbiota was dominated by five phyla: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. After successfully eradicating Hp, the bacterial flora in the stomach recovered to a considerable extent. In the failed eradication group, the flora was similar to the flora in Hp-positive subjects based on the alpha and beta diversities. Among the groups, Curvibacter and Acinetobacter were enriched in the presence of Hp (i.e., failed eradication and Hp-positive groups), suggesting that these two genera could be used as biomarkers in the symbiotic flora in the presence of Hp. SE-CG was characterized by an increase in Firmicutes taxa and a decrease in Proteobacteria taxa compared with N-CG. SE-AG was characterized by a decrease in Firmicutes relative to N-AG. Finally, no differences were found in the pairwise comparisons of nitrate and nitrite reductase functions of the microflora among the four subgroups. Conclusions After Hp infection, the diversity and relative abundance of gastric microflora were significantly decreased. Yet, gastric microbiota could be partially restored to the Hp-negative status after eradication. Still, this effect was incomplete and might contribute to the long-term risks.

Role of Helicobacter pylori and Other Environmental Factors in the Development of Gastric Dysbiosis

Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional characteristics, that allow the optimal growth of characteristic bacteria in this environment. Gastric dysbiosis, which is defined as compositional and functional alterations of the gastric microbiota, can be induced by multiple environmental factors, such as age, diet, multiple antibiotic therapies, proton pump inhibitor abuse, H. pylori status, among others. Although H. pylori colonization has been reported across the world, chronic H. pylori infection may lead to serious consequences; therefore, the infection must be treated. Multiple antibiotic therapy improvements are not always successful because of the lack of adherence to the prescribed antibiotic treatment. However, the abuse of eradication treatments can generate gastric dysbiotic states. Dysbiosis of the gastric microenvironment induces microbial resilience, due to the loss of relevant commensal bacteria and simultaneous colonization by other pathobiont bacteria, which can generate metabolic and physiological changes or even initiate and develop other gastric disorders by non-H. pylori bacteria. This systematic review opens a discussion on the effects of multiple environmental factors on gastric microbial communities.