Association between the relative abundance of gastric microbiota and the risk of gastric cancer: a case-control study (original) (raw)
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Frontiers in cellular and infection microbiology, 2018
Eradication of 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 -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 , and 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 infection compared with negative subjects. As for the differential bacteria, the average relative abundance of was found to significantly decrease from negative (66.16%) to past infection group (33.01%, = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, = 0.027). For and , the average relative abundances showed elevated trend...
Scientific reports, 2016
Inhabitants of Túquerres in the Colombian Andes have a 25-fold higher risk of gastric cancer than inhabitants of the coastal town Tumaco, despite similar H. pylori prevalences. The gastric microbiota was recently shown in animal models to accelerate the development of H. pylori-induced precancerous lesions. 20 individuals from each town, matched for age and sex, were selected, and gastric microbiota analyses were performed by deep sequencing of amplified 16S rDNA. In parallel, analyses of H. pylori status, carriage of the cag pathogenicity island and assignment of H. pylori to phylogeographic groups were performed to test for correlations between H. pylori strain properties and microbiota composition. The gastric microbiota composition was highly variable between individuals, but showed a significant correlation with the town of origin. Multiple OTUs were detected exclusively in either Tumaco or Túquerres. Two operational taxonomic units (OTUs), Leptotrichia wadei and a Veillonella ...
Scientific Reports, 2014
We aimed to characterize microbiota of the gastric mucosa as it progress to intestinal type of cancer. Study included five patients each of non-atrophic gastritis (NAG), intestinal metaplasia (IM) and intestinal-type gastric cancer (GC). Gastric tissue was obtained and DNA extracted for microbiota analyses using the microarray G3 PhyloChip. Bacterial diversity ranged from 8 to 57, and steadily decreased from NAG to IM to GC (p 5 0.004). A significant microbiota difference was observed between NAG and GC based on Unifrac-presence/absence and weighted-Unifrac-abundance metrics of 283 taxa (p , 0.05). HC-AN analyses based on presence/absence of 238 taxa revealed that GC and NAG grouped apart, whereas IM overlapped with both. An ordinated analyses based on weighted-Unifrac distance given abundance of 44 taxa showing significance across categories revealed significant microbiota separation between NAG and GC. This study is the first to show a gradual shift in gastric microbiota profile from NAG to IM to GC. H pyloriinfection is recognized as the main risk factor for distal gastric cancer (GC), although just a fraction of those infected (,3%) ever develop GC, suggesting that other factors also play a role 1. Pathological studies of GC show that this is an inflammation-driven disease, and all factors influencing the mucosal immune response may become involved in this multifactorial model 2. Thus, host genetics, environment, and H. pylori genetics have a role to play. Polymorphisms in inflammation-related genes like IL-1b 511T, Interferon-cR1-56C/T, or in TLRs have been reported to be associated with GC 3 ; reduced consumption of food rich in antioxidants (vegetables, fruits), smoking, alcohol or obesity also increase the risk 4. Most of the above risk factors may have a role on the mucosal inflammatory and immune response, thus modulating the driving force for tissue damage and development of gastric cancer. Distal GC may be of two types, the intestinal and the diffuse, each following different development routes. For the intestinal type, the development model predicted by Correa states that an initial gastric inflammation may go uncontrolled and lead to mucosal atrophy and hypochlorydria, which in turn increases the risk for intestinal metaplasia, dysplasia and finally intestinal type GC 5. Although little is known about the development of diffuse GC, it is accepted that H. pylori and inflammation may also play a role 6. The stomach microbiota may also modulate the intensity and type of inflammatory and immune responses in the gastric mucosa. Studies on the microbiota of the stomach are scarce, and one study found that the human stomach is colonized by a complex microbiota including mainly Proteobacteria, Firmicutes, Actinobacteria and Fusobacterium phyla, and showed clear differences with microbiota described in the mouth and esophagus 7. The study also showed that patients positive for H. pylori culture showed significant increased colonization of Proteobacteria and decrease of Actinobacteria. Initial attempts to compare microbiota in GC vs dyspeptic patients reported no significant differences in bacterial communities, although the authors observed that Streptococcus, Lactobacillus, Veillonella and Prevotella dominated in GC patients 8. We know that H. pylori infection usually does not alter the acid barrier of the gastric mucosa, unless an unregulated inflammatory response in the corpus leads to atrophy and hypochlorydria 9. Alteration of acidity may result in a more permissive milieu for colonization with other bacteria 8. We hypothesize that this shift in microbiota adds to the inflammatory response already in place and increases the risk for more atrophy and
Revista Española de Enfermedades Digestivas, 2016
Background and Aim: Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have unraveled a complex microbial community in the stomach that can also participate in the development of gastric cancer. The aim of this study is to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. Methods: A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer was performed. Results: Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions as well as by Helicobacter pylori infection. In addition, a gradual shift in the gastric microbiota profile from non-atrophic gastritis to intestinal metaplasia, and then to intestinal type cancer appears to exist. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii) as well a decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis). However, no conclusive data suggest if these changes in microbiota are cause or consequence of the process of carcinogenesis. Conclusions: Gastric cancer may be the result of a complex cross-talk between gastric microbiota and Helicobacter pylori. Gastric microbiota appears to play an important role in gastric carcinogenesis, beyond the well-known influence of Helicobacter pylori. Further studies are needed to elucidate the specific role of different microorganisms in the development of gastric cancer. This systematic review aims to provide an update of recent findings related to the role of gastric microbiota in gastric carcinogenesis, focusing on microorganisms besides H. pylori to understand how the constitution of microbiota can influence cancer risk and how it is affected by H. pylori status, possibly explaining its pathogenesis.
Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients
Frontiers in cellular and infection microbiology, 2017
Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter...
Scientific Reports, 2023
Helicobacter pylori (H. pylori) infection has been considered as the main causal factor in gastric carcinogenesis, but other bacterial species may also play an important role in pathophysiology of gastric cancer. The aim of the study was to explore the link between gastric cancer prognosis and the mucosal microbial community in tumorous and adjacent gastric tissue. The bacterial profile was analysed using 16S sequencing (V1-V2 region). Microbial differences were mostly characterized by lower relative abundances of H. pylori in tumorous gastric tissues. Bacterial community and outcome data analysis revealed the genus Fusobacterium and Prevotella significantly associated with worse overall survival in gastric cancer patients. In particular, Fusobacterium was associated with significant increase in hazard ratio in both univariable and multivariable analysis and independently validated using TCMA data. Phylogenetic biodiversity of Fusobacterium species in the stomach revealed F. periodonticum as the most prevalent in healthy subjects, while F. nucleatum was most abundant in patients with gastric cancer. Bacterial community network analysis in gastric cancer suggests substantial complexity and a strong interplay between F. nucleatum and Prevotella. In summary, mucosal microbial community in the stomach was associated with worse overall survival in gastric cancer patients. Strongest negative impact on prognosis was linked to the abundance of F. nucleatum in tumorous specimens, suggesting its translational relevance in management of gastric cancer patients. Identification of Helicobacter pylori (H. pylori) in the stomach has been the initial step in stomach microbiome research since it supplanted the initial hypothesis of the stomach as a sterile niche due to its low pH 1. It then took only a few years to demonstrate the causal link of H. pylori with gastric cancer (GC) 2. Gastric mucosa is strongly assessable for the microbial long-term impact as H. pylori promotes gastric carcinogenesis through the cascade of molecular events along with multistep histopathological events such as chronic gastritis which may progress to atrophic gastritis, intestinal metaplasia, and finally to dysplasia and GC 3,4. Over the last years, various bacteria belonging to different phyla, such as Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria, were discovered in the stomach mucosa 5. Detailed analysis of the gastric microbiome revealed a high microbial diversity with at least 95 different genera present in the stomach habitat. Each individual harbours a unique composition of bacteria. Despite this high diversity, there are dominant bacterial genera in a healthy stomach like Gemella, Veillonella, Neisseria, Fusobacterium, Streptococcus, Prevotella, Pseudomonas, and Actinomyces 6-9. Changes in the microbial community of the stomach are strongly driven by H. pylori positivity and less dependent on genetic factors 6. Overall, studies suggest that increasing amount of stomach bacteria may colonize the stomach mucosa and be associated with GC. Higher abundance of Fusobacterium nucleatum, Clostridium colicanis, and Lactobacillus
Cancer Epidemiology Biomarkers & Prevention, 2014
Background: The human upper digestive tract microbial community (microbiota) is not well characterized and few studies have explored how it relates to human health. We examined the relationship between upper digestive tract microbiota and two cancer-predisposing states, serum pepsinogen I/pepsinogen II ratio (PGI/II; predictor of gastric cancer risk) and esophageal squamous dysplasia (ESD; the precursor lesion of esophageal squamous cell carcinoma; ESCC) in a cross-sectional design.
Gastric Microbiota beyond H. pylori: An Emerging Critical Character in Gastric Carcinogenesis
Biomedicines
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 microb...
Risk factors associated with gastric malignancy during chronic Helicobacter pylori infection
Medical Research Archives, 2020
Chronic Helicobacter pylori (Hp) infection is considered to be the single most important risk factor for the development of gastric adenocarcinoma in humans, which is a leading cause of cancer-related death worldwide. Nonetheless, Hp infection does not always progress to malignancy, and, gastric adenocarcinoma can occur in the absence of detectable Hp carriage, highlighting the complex and multifactorial nature of gastric cancer. Here we review known contributors to gastric malignancy, including Hp virulence factors, featuring the vacuolating cytotoxin (VacA), the cytotoxin-associated gene A (CagA), and other bacterial components that promote chemotaxis, colonization, and the establishment of chronic inflammation. In addition, we discuss host factors including sex, age, and genetic polymorphisms associated with host inflammation. Moreover, we consider environmental variables that influence cancer risk, such as nutritional status, socioeconomic status, and smoking. In addition to these relatively wellstudied contributors to gastric cancer risk, the resident gastric microflora in humans have more recently been proposed as an additional risk factor for disease progression in Hp-infected individuals. Molecular approaches for microbe identification have revealed differences in the gastric microbiota composition between cancer and non-cancerous patients, as well as infected and uninfected individuals. Although the reasons underlying differences in microbial community structures are not entirely understood, gastric atrophy and hypochlorhydria that accompany chronic Hp infection may be a critical driver of gastric dysbiosis that promote colonization of microbes that contribute to increased risk of malignancy. However, definitive evidence that the gastric microbiota influences the emergence of gastric cancer does not exist. In summary, while controversial and unresolved, the importance of the gastric microbiota as a risk factor for gastric malignancy is a vital area of current research.