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Cardiovascular diseases represent one of the first causes of death around the world, and atherosclerosis is one of the first steps in the development of them. Although these problems occur mainly in elderly, the incidence in younger people is being reported, and an undetermined portion of patients without the classic risk factors develop subclinical atherosclerosis at earlier stages of life. Recently, both the H. pylori infection and the intestinal microbiota have been linked to atherosclerosis. The mechanisms behind those associations are poorly understood, but some of the proposed explanations are (a) the effect of the chronic systemic inflammation induced by H. pylori, (b) a direct action over the endothelial cells by the cytotoxin associated gene A protein, and (c) alterations of the lipid metabolism and endothelial dysfunction induced by H. pylori infection. Regarding the microbiota, several studies show that induction of atherosclerosis is related to high levels of Trimethylamine N-oxide. In this review, we present the information published about the effects of H. pylori over the intestinal microbiota and their relationship with atherosclerosis and propose a hypothesis to explain the nature of these associations. If H. pylori contributes to atherosclerosis, then interventions for eradication and restoration of the gut microbiota at early stages could represent a way to prevent disease progression.

Microbial diversity is the most abundant form of life. Next Generation Sequencing technologies provide the capacity to study complex bacterial communities, in which the depth and the bioinformatic tools can influence the results. In this work we explored two different protocols for bacterial classification and abundance evaluation, using 10 bacterial genomes in a simulated sample at different sequencing. Protocol A consisted of metagenome assembly with Megahit and Ray Meta and taxonomic classification with Kraken2 and Centrifuge. In protocol B only taxonomic classification. In both protocols, rarefaction, relative abundance and beta diversity were analyzed. In the protocol A, Megahit had a mean contig length of 1,128 and Ray Meta de 8,893 nucleotides. The number of species correctly classified in all depth assays were 6 out of 10 for protocol A, and 9 out of 10 using protocol B. The rarefaction analysis showed an overestimation of the number of species in almost all assays regardless of the protocol, and the beta diversity analysis results indicated significant differences in all comparisons. Protocol A was more efficient for diversity analysis, while protocol B estimated a more precise relative abundance. Our results do not allow us to suggest an optimal sequencing depth at specie level.

The association between H. pylori infection and coronary artery disease (CAD) is well-known. Alterations in DNA methylation in CAD have been reported, which can be induced by H. pylori through the DNA demethylases (DNMTs). The objective was to analyze the association and interaction of H. pylori infection and DMNT3a gene polymorphisms with premature CAD (pCAD) and subclinical atherosclerosis (SA).The study included 561 patients with pCAD, 318 subjects with SA, and 599 healthy controls. Antibodies against H. pylori and DNMT3a rs13420827, rs752208, and rs1550117 polymorphisms were determined.The pCAD group presented the highest seroprevalence of H. pylori infection (87.7%) compared to the SA (74.5%, p = 1 × 10According to the model adjusted for more confounding variables, H. pylori infection was associated with almost three times the risk of developing pCAD. The rs13420827G allele was associated with an increased risk of H. pylori infection in the whole population and in individuals with SA. Individuals in whom H. pylori infection and the rs13420827GG genotype coexist are at increased risk of pCAD.

The microbiota that inhabits the human body plays an important role in health and disease, by their fundamental role in food digestion, training of the immune system or protection against pathogen colonization. However, when the equilibrium with its host is altered, some diseases like cancer might be promoted. In this review we describe the information collected in recent studies between the microbiota and its association with cancer. We conducted the review of the relation of microbiome and cancer etiology focusing on the gastrointestinal and cervical cancer. The MEDLINE database was used for the search. The gastrointestinal tract harbours a diverse and site specific microbiota, and several studies have demonstrated that perturbation of these microbial communities might be associated with different types of cancer. In particular, alteration of the colorectal, gastric and oesophageal microbiota have been reported associated with cancer development. Likewise, cervical microbiome studies suggest that some members of the cervical microbiota are possible modifiers of the cytokine profile of the cervical microenvironment during the development of cervical lesions and cervical cancer. Larger prospective studies are needed to examine whether microbiome dysbiosis could cause cancer, and to evaluate the utility of microbiome profiles as biomarkers for prevention and early diagnosis. This is an important area of research if we consider that microbiota may be a modifiable factor by the use of pre- and probiotics, in order to prevent cancer evolution or even to potentiate cancer treatment.

Background and Aims: The biliary tract cancer or cholangiocarcinoma (CCA) represents the sixth leading cause of gastrointestinal tumors in the Western world, and mortality varies across the world, with regions such as Chile, Thailand, Japan, and northeastern India presenting the highest rates. CCA may develop in the bile duct, gallbladder, or ampulla of Vater; and risk factors include obesity, parity, genetic background, geographical and environmental factors. Inflammation induced by bacterial infections might play a role in the pathogenesis of CCA. In this work, we investigated whether there is an association between extrahepatic cholangiocarcinoma (ECCA) and infection with S. typhi, H. hepaticus, or H. bilis in a Mexican population. Methods: A total of 194 patients were included and divided into 91 patients with benign biliary pathology (controls) and 103 with ECCA (cases). Tumor samples were taken during endoscopic retrograde cholangiopancreatography by biliary brushing, followed by DNA extraction and PCR testing for infections. Results: We found that 44/103 cases were positive for H. bilis, compared with 19/91 controls (p = 0.002; OR 2.83, 95% CI 1.49–5.32), and when analyzed by sub-site, H. bilis infection was significantly more associated with cancer in the common bile duct (p = 0.0005; OR 3.56, 95% CI 1.77–7.17). In contrast, H. hepaticus infection was not different between cases (17/103) and controls (13/91) (p = 0.82; OR 1.19, 95% CI 0.54–2.60). None of the samples were positive for S. typhi infection. Conclusion: In conclusion, infection with H. bilis but neither H. Hepaticus nor S. typhi was significantly associated with ECCA, particularly with tumors located in the common bile duct.

Helicobacter pylori (HP) genetics may determine its clinical outcomes. Despite high prevalence of HP infection in Latin America (LA), there have been no phylogenetic studies in the region. We aimed to understand the structure of HP populations in LA mestizo individuals, where gastric cancer incidence remains high. The genome of 107 HP strains from Mexico, Nicaragua and Colombia were analyzed with 59 publicly available worldwide genomes. To study bacterial relationship on whole genome level we propose a virtual hybridization technique using thousands of high-entropy 13 bp DNA probes to generate fingerprints. Phylogenetic virtual genome fingerprint (VGF) was compared with Multi Locus Sequence Analysis (MLST) and with phylogenetic analyses of cagPAI virulence island sequences. With MLST some Nicaraguan and Mexican strains clustered close to Africa isolates, whereas European isolates were spread without clustering and intermingled with LA isolates. VGF analysis resulted in increased resolution of populations, separating European from LA strains. Furthermore, clusters with exclusively Colombian, Mexican, or Nicaraguan strains were observed, where the Colombian cluster separated from Europe, Asia, and Africa, while Nicaraguan and Mexican clades grouped close to Africa. In addition, a mixed large LA cluster including Mexican, Colombian, Nicaraguan, Peruvian, and Salvadorian strains was observed; all LA clusters separated from the Amerind clade. With cagPAI sequence analyses LA clades clearly separated from Europe, Asia and Amerind, and Colombian strains formed a single cluster. A NeighborNet analyses suggested frequent and recent recombination events particularly among LA strains. Results suggests that in the new world, H. pylori has evolved to fit mestizo LA populations, already 500 years after the Spanish colonization. This co-adaption may account for regional variability in gastric cancer risk.

The best-studied Helicobacter pylori virulence factor associated with development of peptic ulcer disease or gastric cancer (GC) rather than asymptomatic nonatrophic gastritis (NAG) is the cag pathogenicity island ( cag PAI), which encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into host epithelial cells. Here we used real-time reverse transcription-PCR (RT-PCR) to measure the in vivo expression of genes on the cag PAI and of other virulence genes in patients with NAG, duodenal ulcer (DU), or GC. In vivo expression of H. pylori virulence genes was greater overall in gastric biopsy specimens of patients with GC than in those of patients with NAG or DU. However, since in vitro expression of cagA was not greater in H. pylori strains from patients with GC than in those from patients with NAG or DU, increased expression in GC in vivo is likely a result of environmental conditions in the gastric mucosa, though it may in turn cause more severe pathology. Increased expression of virulence genes in GC may represent a stress response to elevated pH or other environmental conditions in the stomach of patients with GC, which may be less hospitable to H. pylori colonization than the acidic environment in patients with NAG or DU.

Helicobacter pylori strains are the major risk factor for gastric cancer. Strains vary in their content of disease-associated genes, so genome-wide analysis of cancer-isolated strains will help elucidate their pathogenesis and genetic diversity. We present the draft genome sequence of H. pylori isolated from a Mexican patient with intestinal gastric cancer.

Biliary tract cancer or extrahepatic cholangiocarcinoma (ECCA) represents the sixth commonest cause of cancer in the gastrointestinal tract in western countries. We aimed to characterize the microbiota and its predicted associated functions in the biliary tract of ECCA and benign biliary pathology (BBP). Samples were taken from 100 patients with ECCA and 100 patients with BBP by endoscopic cholangio-pancreatography for DNA extraction. Ten patients with ECCA and ten with BBP were selected for microbiota studies using the V4-16S rRNA gene and sequenced in Illumina platform. Microbiota analyses included sample-to-sample distance metrics, ordination/clustering and prediction of functions. Presence of Nesterenkonia sp. and Helicobacter pylori cagA and vacA genes were tested in the 100 ECCA and 100 BBP samples. Phylum Proteobacteria dominated all samples (60.4% average). Ordination multicomponent analyses showed significant microbiota separation between ECCA and BBP (p 0.010). Analyses of 4002 operational taxonomic units with presence variation in at least one category probed a separation of ECCA from BBP. Among these, Nesterenkonia decreased, whereas Methylophilaceae, Fusobacterium, Prevotella, Actinomyces, Novosphingobium and H. pylori increased in ECCA. Predicted associated functions showed increased abundance of H. pylori virulence genes in ECCA. cagA and vacA genes were confirmed by PCR in ECCA and BBP samples. This is the first microbiota report in ECCA and BBP to show significant changes in microbial composition. Bacterial species unusual for human flora were found: Methylophilaceae and Nesterenkonia are reported in hypersaline soils, and Mesorhizobium is a nitrogen-fixing bacterium. Enrichment of virulence genes confirms previous studies suggesting that H. pylori might be associated with ECCA.

Helicobacter pylori infection induces an inflammatory response in the gastric mucosa. Activation of polymorphonuclear leukocytes can produce oxidative damage to gastric tissue through intermediary radicals of oxygen and nitrogen. Vegetable extracts containing polyphenols of the flavonoid family have antibacterial activity, and the flavonoid quercetin possesses anti-H. pylori activity in vitro. The aim of this study was to analyze the effect of oral administration of pure quercetin on inflammation and lipid peroxidation induced by H. pylori in the gastric mucosa of the guinea pig.Sixty days after oral infection with H. pylori guinea pigs received 200 mg/kg of quercetin daily by mouth for 15 days. The infiltration index of inflammatory cells and bacterial density in both the pyloric antrum and corpus were histologically determined by myeloperoxidase histochemistry, hematoxylin-eosin, and modified Giemsa stains. The lipid hydroperoxide content was assessed by the orange xylenol spectrophotometric method.Quercetin significantly reduced the infiltration index of mononuclear cell and bacterial colonization in the pyloric antrum and corpus. In the antrum of infected quercetin-treated animals, a significant diminution of neutrophil leukocyte infiltration was observed compared with the infected nonquercetin-treated animals. In the antrum, the lipid hydroperoxide concentration was significantly decreased in infected animals treated with quercetin, whereas in the corpus no significant differences were observed.Our results indicate that in vivo oral quercetin administration decreases H. pylori infection in the gastric mucosa and reduces both the inflammatory response and lipid peroxidation.