• Gut microbiome
• Inflammation
• Interleukins and chemokines
• Pancreatic ductal adenocarcinoma
• Pancreatitis

• Helicobacter pylori
• meta-analysis
• observational studies
• pancreatic cancer
• systematic review

• glucose metabolism
• pancreatic cancer
• prognosis
• treatment
• tumour microenvironment

• Humans
• Tumor Microenvironment
• Pancreatic Neoplasms/pathology
• Glucose/metabolism
• Carbohydrate Metabolism

• Biliary tract neoplasms
• Dysbiosis
• Early detection of cancer
• Gastrointestinal microbiome
• Microbiota
• Pancreatic Neoplasms
• Tumor microenvironment

• Carcinoma, Pancreatic Ductal/pathology
• Humans
• Microbiota
• Pancreatic Neoplasms/pathology
• RNA, Ribosomal, 16S/genetics
• Syndrome

Background: The association between Helicobacter pylori (H. pylori) infection and pancreatic cancer (PC) risk remains inconclusive. We examined the association between H. pylori antibodies and PC risk in a case-control study at a comprehensive cancer center.

Methods: Multiplex serology using a glutathione S-transferase capture immunosorbent assay in conjunction with fluorescent bead technology was used to measure antibodies to 15 H. pylori proteins in serum or plasma from 131 incident cases with PC or a PC precursor and 131 healthy controls. Reactivity to ≥4 H. pylori proteins was defined as the overall seroprevalence. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at diagnosis/interview, gender, and race.

Results: The majority of the sample was 50 years or older, and from the white race group. Half of the sample were women. Seroprevalence ≥4 of H. pylori proteins was 11.1%. Overall, H. pylori seroprevalence was not associated with PC risk (OR: 0.59; 95% CI: 0.25–1.40). The prevalence of several H. pylori-specific proteins HP537 (OR: 1.78; 95% CI: 0.30–10.51), HP305 (OR: 1.38; 95% CI: 0.61–3.16), and HP410 (OR: 1.31; 95% CI: 0.44–3.96) increased the odds of PC. Similarly, H. pylori-specific proteins HP522 (OR: 0.25; 95% CI: 0.04–1.66), HyuA (OR: 0.49; 95% CI: 0.21–1.14), and HP1564 (OR: 0.63; 95% CI: 0.27–1.51) decreased the odds of PC. However, these findings were not statistically significant at α = 0.05.

Conclusions: Our findings do not support an association between H. pylori and PC risk. Further evaluation of this lack of association is recommended.

• H. pylori
• biomarkers
• cancer
• pancreas
• seroepidemiology

Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.

• Helicobacter pylori
• Pancreatic cancer
• Autoimmune pancreatitis
• Carcinogenesis
• Microbiome
• Molecular mimicry

Pancreatic cancer (PC) continues to be characterized by high morbidity and mortality, owing to the fact, among others, that it is often diagnosed at late stages. Thus far, the search for reliable biomarkers has failed. A number of recent studies have found that there are differences in the microbiota between patients with PC and their healthy counterparts. These differences extend to specific anatomical locations such as the oral cavity, the gastrointestinal tract, and the pancreas itself. The purpose of this review is to outline some of the main differences in the bacterial and fungal populations between patients with PC and their healthy counterparts that have recently come to light. Additionally, the present review aims to highlight the mechanisms underlying the aforementioned microbial associations with PC.

Pancreatic cancer (PC) remains a global health concern with high mortality and is expected to increase as a proportion of overall cancer cases in the coming years. Most patients are diagnosed at a late stage of disease progression, which contributes to the extremely low 5-year survival rates. Presently, screening for PC remains costly and time consuming, precluding the use of widespread testing. Biomarkers have been explored as an option by which to ameliorate this situation. The authors conducted a search of available literature on PubMed to present the current state of understanding as it pertains to the use of microbial biomarkers and their associations with PC. Carriage of certain bacteria in the oral cavity (e.g., Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus sp.), gut (e.g., Helicobacter pylori, Synergistetes, Proteobacteria), and pancreas (e.g., Fusobacterium sp., Enterobacteriaceae, Pseudomonadaceae) has been associated with an increased risk of developing PC. Additionally, the fungal genus Malassezia has likewise been associated with PC development. This review further outlines potential oncogenic mechanisms involved in the microbial-associated development of PC.

• Helicobacter
• Porphyromonas
• cancer
• cancer screening
• dysbiosis
• microbiota
• oral cavity
• pancreas
• pancreatic cancer

• Biomarker
• Pancreatic cancer
• Prediction model
• Screening
• Trend

• chemotherapy response
• microenvironment
• molecular subtypes of pancreatic cancer
• myeloid derived suppressor cells
• pancreatic stellate cells
• regulatory T cells
• tumor-associated macrophages

Pancreatic adenocarcinoma is one of the most lethal cancers in both men and women, with a median five-year survival of around 5%. Therefore, pancreatic adenocarcinoma represents an unmet medical need. Neoplastic diseases, such as pancreatic adenocarcinoma, often are associated with microbiome dysbiosis, termed oncobiosis. In pancreatic adenocarcinoma, the oral, duodenal, ductal, and fecal microbiome become dysbiotic. Furthermore, the pancreas frequently becomes colonized (by Helicobacter pylori and Malassezia, among others). The oncobiomes from long- and short-term survivors of pancreatic adenocarcinoma are different and transplantation of the microbiome from long-term survivors into animal models of pancreatic adenocarcinoma prolongs survival. The oncobiome in pancreatic adenocarcinoma modulates the inflammatory processes that drive carcinogenesis. In this review, we point out that bacterial metabolites (short chain fatty acids, secondary bile acids, polyamines, indole-derivatives, etc.) also have a role in the microbiome-driven pathogenesis of pancreatic adenocarcinoma. Finally, we show that bacterial metabolism and the bacterial metabolome is largely dysregulated in pancreatic adenocarcinoma. The pathogenic role of additional metabolites and metabolic pathways will be identified in the near future, widening the scope of this therapeutically and diagnostically exploitable pathogenic pathway in pancreatic adenocarcinoma.

• LPS
• amino acid metabolites
• bacterial metabolite
• bile acids
• microbiome
• oncobiome
• pancreatic adenocarcinoma
• polyamines
• short chain fatty acid

• eradication
• gastric cancer prevention
• helicobacter pylori
• prevalence
• screening

• China/epidemiology
• Cohort Studies
• Cross-Sectional Studies
• Female
• Helicobacter Infections/diagnosis
• Helicobacter Infections/epidemiology
• Helicobacter pylori/isolation & purification
• Humans
• Male
• Prevalence
• Risk Assessment
• Tibet/epidemiology
• Systematic Reviews as Topic

• human microorganisms
• immunotherapy
• pancreatic cancer
• risk factors
• treatment

• Animals
• Biomarkers, Tumor
• Combined Modality Therapy/methods
• Diagnostic Imaging
• Disease Management
• Disease Susceptibility
• Endoscopy/methods
• Genetic Predisposition to Disease
• Humans
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/etiology
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/therapy
• Pathology, Molecular
• Prognosis
• Risk Factors
• Treatment Outcome

• epidemiology
• helicobacter pylori
• meta-analysis
• prevalence
• tibetan

• Asian People/statistics & numerical data
• China/epidemiology
• China/ethnology
• Ethnicity/statistics & numerical data
• Helicobacter Infections/epidemiology
• Helicobacter Infections/ethnology
• Helicobacter pylori
• Humans
• Prevalence
• Tibet/epidemiology
• Tibet/ethnology
• Meta-Analysis as Topic
• Systematic Reviews as Topic

• Antiapoptotic activity
• Carcinogenesis
• Chronic inflammation
• HBV
• Helicobacter pylori
• Microbiota
• Pancreatic cancer
• Porphyromonas gingivalis

• Carcinogenesis
• Humans
• Microbiota
• Pancreatic Neoplasms/microbiology

• epidemiology
• etiology
• gastric cancer
• infection
• serology
• virus

• Humans
• Meta-Analysis as Topic
• Retroviridae Infections/complications
• Risk Factors
• Stomach Neoplasms/virology
• Systematic Reviews as Topic

• Pancreatic cancer
• biomarker
• dysbiosis
• microbiota

Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.

• Immunotherapy
• Inflammation
• Metabolism
• Microbiome
• Microbiota
• Pancreatic cancer
• Tumor Microenvironment

• Bacteria
• Cancer Immunity
• Immunotherapy
• Microbiome
• Pancreatic Cancer

Helicobacter pylori (H. pylori), an established risk factor for gastric cancer, is suggested to also play a role in the development of pancreatic cancer; however, the association remains inconclusive. We examined this association among Japanese men and women. H. pylori and atrophic gastritis (AG) status were determined serologically, using blood sample collected during health checkups. A total of 20,116 subjects enrolled in the Japan Public Health Center-based Prospective Study Cohort II with available data on H. pylori seropositivity (anti-H. pylori) and AG were followed until the end of 2010. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI), using the information from the baseline survey. During 320,470 person-years of follow-up, 119 cases of pancreatic cancer were identified. No statically significant increase or decrease in pancreatic cancer risk was observed for H. pylori and AG status, independently or in combination. In a multivariable-adjusted model, we observed a non-significant decrease in the risk among those who had AG but were anti-H. pylori seronegative (HR 0.57, 95% CI 0.31–1.03). In a stratified analysis, we observed a statistically significant increased risk of pancreatic cancer for AG+ (HR 3.64, 95% CI 1.37–9.66), and AG+/anti-H. pylori− or AG+/anti-H. pylori+ (HR 5.21, 95% CI 1.14–23.87) among current smokers. Non-smokers in all categories of AG and anti-H. pylori showed a non-statistical decrease in the risk. There was no statistically significant interaction between H. pylori infection, AG status, and smoking status. Our findings suggest H. pylori seropositivity and AG, individually or in combination, are not associated with the risk of pancreatic cancer in a general Japanese population. Among current smokers, pancreatic cancer risk increased with AG, regardless of H. pylori infection status.

• helicobacter pylori infection
• cholelithiasis
• chronic cholecystitis
• meta-analysis

• atrophic gastritis
• cytotoxin-associated gene a
• epidemiology
• helicobacter pylori
• pancreatic cancer

• Gastritis, Atrophic/epidemiology
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Humans
• Pancreatic Neoplasms/epidemiology
• Prospective Studies

Background: Several studies have suggested that Helicobacter pylori (H. pylori) infection is a risk factor for colorectal cancer (CRC), while others have not confirmed this hypothesis. This work aimed to assess the relation of CRC with H. pylori seropositivity and with seropositivity to 16 H. pylori proteins, in the MultiCase-Control study, MCC-Spain.

Methods: MCC-Spain is a multicase-control study carried out in Spain from 2008 to 2013. In total, 2,140 histologically-confirmed incident CRC cases and 4,098 population-based controls were recruited. Controls were frequency-matched by sex, age, and province. Epidemiological data were collected through a questionnaire fulfilled by face-to-face interviews and a self-administered food-frequency questionnaire. Seroreactivities against 16 H. pylori proteins were determined in 1,488 cases and 2,495 controls using H. pylori multiplex serology. H. pylori seropositivity was defined as positivity to ≥4 proteins. Multivariable logistic regression mixed models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results:H. pylori seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71–1.16). Among H. pylori seropositive subjects, seropositivity to Cagδ showed a lower CRC risk, and risk decreased with increasing number of proteins seropositive. Seropositivity to the most recognized virulence factors, CagA and VacA, was not associated with a higher CRC risk. No statistically significant heterogeneity was identified among tumor sites, although inverse relations were stronger for left colon cancer. An interaction with age and sex was found: H. pylori seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women.

Conclusions: Our results suggest that neither H. pylori seropositivity, nor seropositivity to the virulence factor CagA are associated with a higher CRC risk. A possible effect modification by age and sex was identified.

• Helicobacter pylori
• bacterial infections
• chronic infection
• colorectal neoplasm
• multiplex serology
• non-infectious diseases

To review microbiome alterations associated with pancreatic cancer, its potential utility in diagnostics, risk assessment, and influence on disease outcomes.

A comprehensive literature review was conducted by all-inclusive topic review from PubMed, MEDLINE, and Web of Science. The last search was performed in October 2016.

Diverse microbiome alterations exist among several body sites including oral, gut, and pancreatic tissue, in patients with pancreatic cancer compared to healthy populations.

Pilot study successes in non-invasive screening strategies warrant further investigation for future translational application in early diagnostics and to learn modifiable risk factors relevant to disease prevention. Pre-clinical investigations exist in other tumor types that suggest microbiome manipulation provides opportunity to favorably transform cancer response to existing treatment protocols and improve survival.

• Pancreatic Cancer
• Human microbiome
• Biomarkers, cancer
• Cancer screening tests
• Treatment effectiveness

• Carcinogenesis
• Helicobacter pylori/pathogenicity
• Humans
• Microbiota
• Pancreas/microbiology
• Pancreas/pathology
• Pancreatic Neoplasms/microbiology
• Pancreatic Neoplasms/pathology
• Risk Assessment
• Risk Factors

Pancreatic ductal adenocarcinoma is one of the most lethal types of tumour, and its incidence is rising worldwide. Although survival can be improved when these tumours are detected at an early stage, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. The only prognostic biomarker approved by the FDA to date is carbohydrate antigen 19-9 (CA19-9); however, the specificity of this biomarker has been called into question, and diagnosis is usually based on clinical parameters. Tumour size, degree of differentiation, lymph node status, presence of distant metastasis at diagnosis, protein levels of KI-67 or C-reactive protein, and mutational status of P53, KRAS, or BRCA2 are the most useful biomarkers in clinical practice. In addition to these, recent translational research has provided evidence of new biomarkers based on different molecules involved in endoplasmic reticulum stress, epithelial-to-mesenchymal transition, and noncoding RNA panels, especially microRNAs and long noncoding RNAs. These new prospects open new paths to tumour detection using minimally or noninvasive techniques such as liquid biopsies. To find sensitive and specific biomarkers to manage these patients constitutes a challenge for the research community and for public health policies.

The discovery of Helicobacter pylori (H. pylori) colonization of the stomach and its pathogenic effects is a crucial landmark in modern gastroenterology. There have been many studies reporting that the natural history of many disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma are linked with the presence of this bacterium. Moreover, H. pylori is often involved in the pathogenic processes of a variety of extra-gastric diseases, especially those characterized by persistent and low grade systemic inflammation. The proposed mechanisms ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This paper will review the results of the most important studies on the association of H. pylori infection with extra-gastric diseases, such as autoimmune, neoplastic, cardiovascular and other related disorders, as well as possible mechanisms implicated in the pathogenesis of these extra-gastric diseases.

• Helicobacter pylori
• Autoimmune diseases
• Neoplastic diseases
• Cardiovascular diseases

• chronic atrophic gastritis
• colon cancer
• gastric cancer
• helicobacter pylori
• pancreatic cancer

• Aged
• Antibodies, Bacterial/blood
• Antigens, Bacterial/immunology
• Bacterial Proteins/immunology
• Cohort Studies
• Colonic Neoplasms/epidemiology
• Colonic Neoplasms/microbiology
• Female
• Follow-Up Studies
• Gastritis, Atrophic/complications
• Gastritis, Atrophic/microbiology
• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/epidemiology
• Pancreatic Neoplasms/microbiology
• Prevalence
• Risk Factors
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/microbiology