Comparative Genomics ofH. pyloriand Non-PyloriHelicobacterSpecies to Identify New Regions Associated with Its Pathogenicity and Adaptability

The genusHelicobacteris a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species.Helicobacter pylori(H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings ofH. pylorithat are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representativeH. pyloriand 24 non-pylori Helicobactergenomes. There were 1173 conserved protein families ofH. pyloriand 673 of all 99Helicobactergenus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of theH. pyloribut lacked in non-pylori Helicobacterspecies. The operons, genes, and sRNAs within theH. pyloriunique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship.

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Predictors for development of complete and incomplete intestinal metaplasia (IM) associated with H. pylori infection: A large-scale study from low prevalence area of gastric cancer (IM-HP trial)

PLoS ONE ◽

10.1371/journal.pone.0239434 ◽

2020 ◽

Vol 15 (10) ◽

pp. e0239434

Author(s):

Natsuda Aumpan ◽

Ratha-Korn Vilaichone ◽

Pongjarat Nunanan ◽

Soonthorn Chonprasertsuk ◽

Sith Siramolpiwat ◽

...

Keyword(s):

Gastric Cancer ◽

Intestinal Metaplasia ◽

Large Scale ◽

Large Scale Study ◽

H Pylori ◽

Low Prevalence

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Strategies for Prevention of Gastric Cancer: Progress from Mass Eradication Trials

Digestive Diseases ◽

10.1159/000445229 ◽

2016 ◽

Vol 34 (5) ◽

pp. 500-504 ◽

Cited By ~ 5

Author(s):

Kentaro Sugano

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

Large Scale ◽

Eradication Therapy ◽

Subsequent Development ◽

International Agency ◽

Preventive Strategy ◽

Implementation Phase ◽

The Government ◽

H Pylori

Background:Helicobacter pylori infection is the cause of the majority of gastric cancer. Meta-analyses on several interventional trials, irrespective of the target population, unanimously demonstrated the benefit of eradication therapy in reducing the occurrence of gastric cancer. Based on the evidence for the preventive effects on gastric cancer by eradication therapy in the general population, the International Agency for Research on Cancer advocated eradication of H. pylori as the primary preventive strategy for gastric cancer. Consensus reports on H. pylori gastritis by experts also recommended eradication of H. pylori as the strategy for prevention of gastric cancer. Key Messages:H. pylori is responsible for the majority of gastric cancer. As the eradication of the infection has been shown to reduce subsequent development of gastric cancer, a number of large-scale controlled trials involving a large number of subjects are currently underway in various countries to further verify the feasibility and effects of H. pylori eradication on gastric cancer prevention. However, such studies might be considered unethical as we already knew that the criminal role of H. pylori in gastric carcinogenesis. In Japan, rather than conducting clinical trials, the government adopted insurance coverage for H. pylori gastritis irrespective of symptoms. This policy brought about a massive surge in eradication therapy, which will ensue in a drastic reduction in the prevalence of H. pylori by 2030 as well as gastric cancer. Conclusions: Primary prevention of gastric cancer is now moving into implementation phase in Japan and will be spreading in other counties where long-term clinical trials have started.

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Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area

Cancers ◽

10.3390/cancers11040504 ◽

2019 ◽

Vol 11 (4) ◽

pp. 504 ◽

Cited By ~ 14

Author(s):

Boldbaatar Gantuya ◽

Hashem B. El-Serag ◽

Takashi Matsumoto ◽

Nadim J. Ajami ◽

Khasag Oyuntsetseg ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Bacterial Species ◽

Rrna Gene ◽

Linear Discriminant ◽

Haemophilus Parainfluenzae ◽

Increased Risk ◽

Comparison Groups ◽

H Pylori ◽

Gastric Microbiota

Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplicon sequencing to profile the gastric microbiota according to comparison groups. These results demonstrate that the HpP group had significantly lower bacterial richness by the operational taxonomic unit (OTU) counts, and Shannon and Simpson indices as compared to HpN or controls. The linear discriminant analysis effect size analysis showed the enrichment of Firmicutes, Fusobacteria, Bacteroidetes and Actinobacteria at phylum level in the HpN group. In the age-adjusted multivariate analysis, Streptococcus sp. and Haemophilus parainfluenzae were at a significantly increased risk for HpN (odds ratio 18.9 and 12.3, respectively) based on abundance. Treponema sp. was uniquely found in HpN based on occurrence. In this paper, we conclude that Streptococcus sp., Haemophilus parainfluenzae and Treponema sp. are candidate pathogenic bacterial species for HpN. These results if confirmed may have important clinical implications.

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BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms222312724 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12724

Author(s):

Rina Fujiwara-Tani ◽

Ayaka Okamoto ◽

Hiroyuki Katsuragawa ◽

Hitoshi Ohmori ◽

Kiyomu Fujii ◽

...

Keyword(s):

Gastric Cancer ◽

Granulation Tissue ◽

Braf Mutation ◽

Large Scale ◽

Hyperplastic Polyp ◽

P53 Protein ◽

Protein Accumulation ◽

Low Grade ◽

Mucin Phenotype ◽

H Pylori

Gastric hyperplastic polyps (GHP) are frequently found to be benign polyps and have been considered to have a low carcinogenic potential. The characteristics of the hyperplastic polyp-associated gastric cancer (HPAGC) remain unclear. Therefore, we analyzed samples from 102 GHP patients and identified 20 low-grade atypical GHPs (19.6%), 7 high-grade atypical GHPs (6.9%), and 5 intramucosal cancer samples (4.9%). GHP atypia was more common in the elderly and increased with increasing polyp size. In particular, polyps larger than 1 cm were associated with a higher grade and cancer. Furthermore, mucus production decreased with increasing atypia. Although no correlation was found between atypia and Helicobacter pylori infection or intestinal metaplasia, enhanced proliferative ability (Ki-67) did correlate with atypia, as did nuclear 8-hydroxy-2’-deoxyguanosine levels. Interestingly, 4-hydroxynonenal levels in granulation tissue and the area ratio of granulation tissue within polyps also correlated with GHP atypia. In five cases of HPAGC, three cases exhibited caudal type homeobox transcription factor (CDX2)-positive cells and a mixed mucin phenotype, which is considered to be related to H. pylori infection. By contrast, two cases were CDX2 negative, with a gastric mucin phenotype, and H. pylori infection was not observed in the tumor or the surrounding mucosa. In these cases, a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (V600E) was detected. All cancer samples showed high stemness and p53 protein accumulation, but no KRAS mutations. The molecular and phenotypic characteristics of the cases characterized by BRAF mutations may represent a novel subtype of HPAGC, reflecting a conserved pathway to oncogenesis that does not involve H. pylori infection. These findings are worthy of further investigation in a large-scale study with a substantial cohort of HPAGC patients to establish their clinical significance.

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Photocatalytic Inactivation of Bioaerosols by TiO2 Coated Membrane

International Journal of Chemical Reactor Engineering ◽

10.2202/1542-6580.1236 ◽

2005 ◽

Vol 3 (1) ◽

Cited By ~ 14

Author(s):

Amrita Pal ◽

Xu Min ◽

Liya E Yu ◽

Simo O Pehkonen ◽

Madhumita B. Ray

Keyword(s):

Bacillus Subtilis ◽

Large Scale ◽

Indoor Air Pollution ◽

Bacterial Species ◽

Public Health Problem ◽

Continuous Systems ◽

Gram Positive ◽

Gram Negative ◽

Tropical Regions ◽

E Coli

Indoor air pollution by microbial contaminants is increasingly receiving attention as a public health problem. Under a suitable environment, such as in heating, ventilation and air conditioning (HVAC) system, airborne bacteria are able to proliferate and grow causing various allergies and illnesses. This can be particularly serious in tropical regions due to high relative humidity and warm temperatures all round the year. Application of photocatalysis using UV-A and TiO2 to inactivate air-borne bacteria is relatively new and systematic parametric study is required for the engineering design of a process based on this technology. This study investigates the effects of TiO2 mediated inactivation of various bacterial species in batch and continuous systems using different TiO2 loadings and radiation intensities. Gram-negative bacteria, E. coli and two Gram-positive bacteria, Microbacterium sp. and Bacillus subtilis were used for the inactivation studies. In both systems, inactivation rates of Gram-negative E. coli are higher than the Gram-positive Bacillus subtilis and Microbacterium sp. and the inactivation rates increased in presence of TiO2 for all bacteria. Depending on the type of bacteria, TiO2 loading and light intensity, an increase of 1.3-5.8 times in the inactivation rates was obtained from those in the absence of TiO2. The inactivation rates in the batch and continuous systems were reasonably comparable. Inactivation rates in the continuous system are somewhat higher than those in the batch system due to the unaccounted loss of bacteria via adsorption and settling on the reactor walls in the flow system. The study demonstrates an approach that can be used for the designing of large scale systems for the treatment of bioaerosol.

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Genome Sequencing Reveals a Phage in Helicobacter pylori

mBio ◽

10.1128/mbio.00239-11 ◽

2011 ◽

Vol 2 (6) ◽

Cited By ~ 39

Author(s):

Philippe Lehours ◽

Filipa F. Vale ◽

Magnus K. Bjursell ◽

Ojar Melefors ◽

Reza Advani ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Human Population ◽

Bacterial Genome ◽

Uv Treatment ◽

Integrase Gene ◽

Content Type ◽

Geographic Regions ◽

H Pylori

ABSTRACT Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, likely to grow as more genomes are sampled. Here we describe the draft genome sequence (63 contigs; 26× mean coverage) of H. pylori strain B45, isolated from a patient with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The major finding was a 24.6-kb prophage integrated in the bacterial genome. The prophage shares most of its genes (22/27) with prophage region II of Helicobacter acinonychis strain Sheeba. After UV treatment of liquid cultures, circular DNA carrying the prophage integrase gene could be detected, and intracellular tailed phage-like particles were observed in H. pylori cells by transmission electron microscopy, indicating that phage production can be induced from the prophage. PCR amplification and sequencing of the integrase gene from 341 H. pylori strains from different geographic regions revealed a high prevalence of the prophage (21.4%). Phylogenetic reconstruction showed four distinct clusters in the integrase gene, three of which tended to be specific for geographic regions. Our study implies that phages may play important roles in the ecology and evolution of H. pylori. IMPORTANCE Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population, and while most of the infected individuals do not develop disease, H. pylori infection doubles the risk of developing gastric cancer. An abundance and diversity of viruses (phages) infect microbial populations in most environments and are important mediators of microbial diversity. Our finding of a 24.6-kb prophage integrated inside an H. pylori genome and the observation of circular integrase gene-containing DNA and phage-like particles inside cells upon UV treatment demonstrate that we have discovered a viable H. pylori phage. The additional finding of integrase genes in a large proportion of screened isolates of diverse geographic origins indicates that the prevalence of prophages may have been underestimated in H. pylori. Since phages are important drivers of microbial evolution, the discovery should be important for understanding and predicting genetic diversity in H. pylori.

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Transient and Persistent Gastric Microbiome: Adherence of Bacteria in Gastric Cancer and Dyspeptic Patient Biopsies after Washing

Journal of Clinical Medicine ◽

10.3390/jcm9061882 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1882 ◽

Cited By ~ 1

Author(s):

Malene R. Spiegelhauer ◽

Juozas Kupcinskas ◽

Thor B. Johannesen ◽

Mindaugas Urba ◽

Jurgita Skieceviciene ◽

...

Keyword(s):

Gastric Cancer ◽

Bacterial Diversity ◽

Large Scale ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Peptic Ulcers ◽

Gastric Biopsies ◽

H Pylori ◽

Gastric Microbiota

Helicobacter pylori is a common colonizer of the human stomach, and long-term colonization has been related to development of atrophic gastritis, peptic ulcers and gastric cancer. The increased gastric pH caused by H. pylori colonization, treatment with antibiotics or proton pump inhibitors (PPI) may allow growth of other bacteria. Previous studies have detected non-Helicobacter bacteria in stomach biopsies, but no conclusion has been made of whether these represent a transient contamination or a persistent microbiota. The aim of this study was to evaluate the transient and persistent bacterial communities of gastric biopsies. The washed or unwashed gastric biopsies were investigated by cultivation and microbiota analysis (16S rRNA gene-targeted amplicon sequencing) for the distribution of H. pylori and other non-Helicobacter bacteria. The number of cultured non-Helicobacter bacteria decreased in the washed biopsies, suggesting that they might be a transient contamination. No significant differences in the bacterial diversity were observed in the microbiome analysis between unwashed and washed biopsies. However, the bacterial diversity in biopsies shown H. pylori-positive and H. pylori-negative were significantly different, implying that H. pylori is the major modulator of the gastric microbiome. Further large-scale studies are required to investigate the transient and persistent gastric microbiota.

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Role of vitamin C in gastric cancer

10.33118/oap.radiol/01.001 ◽

2018 ◽

Vol 01 (1) ◽

Author(s):

Takalkar U Vidyadhar

Keyword(s):

Gastric Cancer ◽

Vitamin C ◽

Gastric Juice ◽

Oxidative Dna Damage ◽

Preventive Measure ◽

Dietary Factors ◽

Preventive Strategy ◽

H Pylori

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

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TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.274.tlr ◽

2018 ◽

Vol 27 (4) ◽

pp. 363-369 ◽

Cited By ~ 4

Author(s):

Gintare Dargiene ◽

Greta Streleckiene ◽

Jurgita Skieceviciene ◽

Marcis Leja ◽

Alexander Link ◽

...

Keyword(s):

Gastric Cancer ◽

Atrophic Gastritis ◽

Genetic Polymorphisms ◽

Association Studies ◽

Control Group ◽

Similar Distribution ◽

Genome Wide Association Studies ◽

Increased Risk ◽

Infection Susceptibility ◽

H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

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Social inequality in the evolution of human societies

Sociology: Theory, Methods, Marketing ◽

10.15407/sociology2019.02.098 ◽

2019 ◽

pp. 98-120

Author(s):

Georgi Derluguian

Keyword(s):

Social Inequality ◽

Large Scale ◽

Human Beings ◽

Mass Violence ◽

Public And Private ◽

Tangible Assets ◽

Transition To Agriculture ◽

New Institutions ◽

High Level ◽

Political Economic

The author develops ideas about the origin of social inequality during the evolution of human societies and reflects on the possibilities of its overcoming. What makes human beings different from other primates is a high level of egalitarianism and altruism, which contributed to more successful adaptability of human collectives at early stages of the development of society. The transition to agriculture, coupled with substantially increasing population density, was marked by the emergence and institutionalisation of social inequality based on the inequality of tangible assets and symbolic wealth. Then, new institutions of warfare came into existence, and they were aimed at conquering and enslaving the neighbours engaged in productive labour. While exercising control over nature, people also established and strengthened their power over other people. Chiefdom as a new type of polity came into being. Elementary forms of power (political, economic and ideological) served as a basis for the formation of early states. The societies in those states were characterised by social inequality and cruelties, including slavery, mass violence and numerous victims. Nowadays, the old elementary forms of power that are inherent in personalistic chiefdom are still functioning along with modern institutions of public and private bureaucracy. This constitutes the key contradiction of our time, which is the juxtaposition of individual despotic power and public infrastructural one. However, society is evolving towards an ever more efficient combination of social initiatives with the sustainability and viability of large-scale organisations.

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