Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer

BACKGROUND Helicobacter pylori(H.pylori)infection is closely associated with gastrointestinal diseases.Our preliminary studies have indicated that H.pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer(GU)or duodenal ulcer(DU).AIM To investigate the contributions of H.pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases.METHODS Patients with H.pylori infection and either GU or DU,and healthy individuals without H.pylori infection were included.Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing.The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed.RESULTS Compared with that in the healthy individuals,the gastric mucosal microbiota in the H.pylori-positive patients with GU was dominated by H.pylori,with signi-ficantly reduced biodiversity.The intergroup differential functions,which were enriched in the H.pylori-positive GU patients,were all derived from H.pylori,particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones.A significant enrichment of the uibE gene was detected in the synthesis pathway.There was no significant difference in microbial diversity between the H.pylori-positive DU patients and healthy controls.CONCLUSION H.pylori infection significantly alters the gastric microbiota structure,diversity,and biological functions,which may be important contributing factors for GU.

Rare case of Helicobacter pylori -related gastric ulcer: Malignancy or pseudomorphism?

Helicobacter pylori (H. pylori ) is a pathogen and the most frequent cause of gastric ulcers. There is also a close correlation between the prevalence of H. pylori infection and the incidence of gastric cancer. We present the case of a 38-year-old woman referred by her primary care physician for screening positron emission tomography-computed tomography (PET-CT), which showed a nodular strong accumulation point with standardized uptake value 5.6 in the gastric fundus. Gastroscopy was then performed, and a single arched ulcer, 12 mm in size, was found in the gastric fundus. Histopathological examination of the lesion revealed chronic mucosal inflammation with acute inflammation and H. pylori infection. There was an obvious mitotic phase with widespread lymphoma. Formal anti-H. pylori treatment was carried out. One month later, a gastroscopy showed a single arched ulcer, measuring 10 mm in size in the gastric fundus. Histopathological examination revealed chronic mucosal inflammation with acute inflammation and a very small amount of H. pylori infection. The mitotic phase was 4/10 high power field, with some heterotypes and an obvious nucleolus. Follow-up gastroscopy 2 mo later showed the gastric ulcer in stage S2. The mucosal swelling had markedly improved. The patient remained asymptomatic, and a follow-up PET-CT was performed 6 mo later. The nodular strong accumulation point had disappeared. Follow-up gastroscopy showed no evidence of malignant cancer. H. pylori-associated severe inflammation can lead to neoplastic changes in histiocytes. This underscores the importance of eradicating H. pylori , especially in those with mucosal lesions, and ensuring proper follow-up to prevent or even reverse early gastric cancer.

Helicobacter heilmannii sensu stricto-related gastric ulcers:A case report

A spiral bacterium (SH9), morphologically different from Helicobacter pylori (H. pylori), was found in a 62-year-old woman’s gastric mucosa. Gastroscopic examination revealed multiple gastric ulcers near the pyloric ring; mapping gastric biopsy showed mild mononuclear infiltration with large lymphoid follicles in the antrum, without corpus atrophy. Urea breath test and H. pylori culture were negative, but Giemsa staining of biopsies revealed tightly coiled bacteria that immunostained with anti-H. pylori antibody. Sequencing of SH9 16S rRNA and the partial urease A and B subunit genes showed that the former sequence had highest similarity (99%; 1302/1315 bp) to Helicobacter heilmannii (H. heilmannii) sensu stricto (H. heilmannii s.s.) BC1 obtained from a bobcat, while the latter sequence confirmed highest similarity (98.3%; 1467/1493 bp) to H. heilmannii s.s. HU2 obtained from a human. The patient was diagnosed with multiple gastric ulcers associated with H. heilmannii s.s. infection. After triple therapy (amoxicillin, clarithromycin, and lansoprazole) with regimen for eradicating H. pylori, gastroscopy showed ulcer improvement and no H. heilmannii s.s. upon biopsy.

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for “surgical disease” or for “Sippy” diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.

Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection

AIM:To evaluate the incidence and clinical characteristics of gastric cancer(GC) in peptic ulcer patients with Helicobacter pylori(H.pylori) infection.METHODS:Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed.Those with previous gastric ulcer(GU) and H.pylori infection were assigned to the Hp GU-GC group(n = 86) and those with previous duodenal ulcer(DU) disease and H.pylori infection were assigned to the Hp DUGC group(n = 35).The incidence rates of GC in the Hp GU-GC and Hp DU-GC groups were analyzed.Data on demographics(age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia(IM)], outcome of eradication therapy for H.pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed.Univariate and multivariate analyses were performed to identify factors influencing GC development.The relative risk of GC was evaluated using a Cox proportional hazards model.RESULTS:The incidence rates of GC were 3.60%(86/2387) in the Hp GU-GC group and 1.66%(35/2098) in the Hp DU-GC group.The annual incidence was 0.41% in the Hp GU-GC group and 0.11% in the Hp DUGC group.The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the Hp GU-GC group than in the Hp DU-GC group(86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P < 0.05).In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H.pylori infection were significantly associated with the development of GC(P < 0.05).There was no significant difference in the prognosis of GC patients between the Hp GU-GC and Hp DU-GC groups(P = 0.347).The relative risk of GC development in the Hp GUGC group compared to that of the Hp DU-GC group,after correction for age and gender,was 1.71(95%CI:1.09-2.70;P=0.02).CONCLUSION:GU patients with H.pylori infection had higher GC incidence rates and relative risks.Atrophy of surrounding mucosa,IM and eradication therapy were associated with GC.

Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer?

AIM:To investigate the effects of Helicobacter pylori (H pylori)eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer. METHODS:A multicenter prospective cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture,Japan.The study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication(eradication group)or conventional antacid therapy(non-eradication group).Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and questionnaire surveys,as well as Yamagata Prefectural Cancer Registry data,and was compared between the two groups and by results of H pylori therapy.RESULTS:A total of 4133 patients aged between 13 and 91 years(mean 52.9 years)were registered,and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 years.The sex-and age-adjusted incidence ratio of gastric cancer in the eradication group, as compared with the non-eradication group,was 0.58 (95%CI:0.28-1.19)and ratios by follow-up period(<1 year,1-3 years,>3 years)were 1.16(0.27-5.00),0.50 (0.17-1.49),and 0.34(0.09-1.28),respectively.Longer follow-up tended to be associated with better prevention of gastric cancer,although not to a significant extent.No significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy(32/2451 patients,1.31%)and those with treatment failure(11/639 patients,1.72%).Among patients with duodenal ulcer,which is known to be more prevalent in younger individuals,the incidence of gastric cancer was significantly less in those with successful eradication therapy(2/845 patients,0.24%)than in those with treatment failure(3/216 patients,1.39%). CONCLUSION:H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer.

Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer

AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori -infected populations. METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this metaanalysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries. CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.

Association of Helicobacter pylori IgA antibodies with the risk of peptic ulcer disease and gastric cancer

AIM: To compare the prevalence of Helicobacter pylori (Hpylori) IgG and IgA antibodies between adult subjects,with defined gastric diseases, nondefined gastric disorders and those representing the population.METHODS: Data on H pylori IgG and IgA antibodies,determined by enzyme immunoassay, were analyzed in 3 252 subjects with DGD including 482 patients with gastric ulcer, 882 patients with duodenal ulcer, 1 525patients with chronic gastritis only and 363 subjects with subsequent gastric cancer, 19 145 patients with NoDg and4 854 POPUL subjects. The age-adjusted prevalences were calculated for 1- and 20-year age cohorts.RESULTS: The prevalences of IgG antibodies were equally high (89-96%) in all 20-year age cohorts of the DGD groups, whereas the prevalences of IgG antibodies were lower and increased by age in the POPUL and NoDg groups. The prevalences of IgA antibodies were also higher in the DGD groups; among them CA (84-89%) and GU groups (78-91%) showed significantly higher prevalences than DU (68-77%) and CG patients (59-74%) (OR 2.49, 95%CI 1.86-3.34 between the GU and DU groups). In the CA, GU, and DU groups, the IgA prevalences showed only minor variation according to age, while they increased by age in the CG, POPUL, and NoDg groups (P≤0.0001). The IgA response, but not the IgG response, was associated with an increased risk of CA (OR 2.41, 95%CI 1.79-3.53) and GU (OR 2.57,95%CI 1.95-3.39) in comparison with CG patients.CONCLUSION: An IgA antibody response during H pylori infection is significantly more common in CA and GU patients as compared with CG patients.

Oral administration of hyperoxygenated solution for the prophylaxis of gastric ulceration induced by stress or Helicobacter pylori

Oxygen was first discovered by Sweden chemist Scheele in 1773 and convinced as an essential factor for living by French scientists in 1777.To tackle with different hypoxic emergencies,corresponding medical approaches,e.g.mask or nasal catheter oxygen inhalation,breathing machine,hyperbaric oxygen therapy etc.,have been contrived in succession.However,one mortal trouble exists in all these conventional ways,i.e.they must rely on the ventilation and gas exchange via lungs,thus not being able to promptly render oxygen to specific hypoxia tissues.Hyperoxygenated solution(HOS),a new kind of medical liquid which can be orally taken or intravenously administrated,has been widely applied as an auxiliary method of offering oxygen in China.A large number of experiments have proved its validity in the treatment of myocardial and cerebral ischemia/reperfusion injury,nerve lesions,shock,respiratory diseases,neonatal hypoxia and so forth.These findings suggest that HOS might not only play a role of increasing oxygen pressure in local region,but also conspicuously contribute to improving the pathologic process of hypoxia,which coincidently is the vital link in stress-induced lesions in the gastrointestinal tract.Additionally,Helicobacter pylori(H.pylori),a kind of microaerophilic(anaerobic)bacterium which can hardly survive in an aerobic atmosphere,has also been identified as an independent risk factor for the occurrence and development of ulceration.Considering the etiology of peptic ulceration and the features of HOS,we hypothesize that drinking HOS might prevent gastric ulceration caused by stress or anaerobic H.pylori.

Helicobacter Pylori Infection: Epidemiological, Clinical and Endoscopic Aspects in Brazzaville

Introduction: Helicobacter pylori infection is a real health problem worldwide. It is the most common chronic bacterial infection in the world, and is particularly prevalent in developing countries. Objective: To determine the frequency of Helicobacter pylori infection and to study the epidemiological, clinical and endoscopic characteristics associated with this infection in Brazzaville. Patients and Methods: This was a descriptive cross-sectional study conducted from January to November 2020, i.e. 11 months. This work focused on 100 symptomatic patients over 18 years old referred for upper GI endoscopy. Gastric biopsies for biological study by urease test and molecular study by real time PCR technique were taken. Results: With a mean age of 46.32 ± 15.20 years, the frequency of Hp infection was 91%, with a female predominance of 53%. The sex ratio was 0.92. The average age was 46.32 ± 15.20 years. Carriage of the infection was more important in households with more than 3 persons, in patients consuming public tap water and in those using both types of sanitary facilities. Endoscopy was indicated for epigastralgia in 93.1% of cases. About 56.14% of the infected patients had normal mucosa versus 12.28% with ulcerated lesions and 22.81% with gastritis. Conclusion: The prevalence of Helicobacter pylori infection is significant in Congo, justifying early detection in order to improve management.

Mechanisms involved in Helicobacter pylori induced duodenal ulcer disease:an overview

Duodenal ulcer (DU) can be developed viaseveral different mechanisms.Hypersecretion ofgastric acid is,however,a common denominator.Amassive hypersecretion of acid can by itself evoke aDU,e.g.in the Zollinger-Ellison syndrome.Irrespective of the mechanism behind thedevelopment of a DU,powerful antisecretorytreatment will heal the ulcer and preventrecurrence.

Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization

AIM： To determine the role of interleukin （IL）-17 in gastric ulcerogenesis. METHODS： Thirty-six gastric ulcer （GU） patients and 29 non-ulcer （NU） patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 ug/mL phytohemagglutinin-P （PHA）, histological examination, and Helicobacter pylori（Hpylon） culture. IL-17 and IL-8 protein levels in culture supematants were assayed by ELISA. IL- 17 mRNA expression was analyzed by reverse transcriptasepolymerase chain reaction （RT-PCR）. Hpylori cagA and vacA status was assessed by reverse hybridization using a line probe assay （UPA）. IL-8 levels in culture supematants were assayed after AGS cells were co-cultured with Hpylori strain 26 695 or recombinant human （rh） IL-17. RESULTS： All 36 GU patients and 15 of 29 NU patients were found to be Hpy/or/-positive, while 14 NU patients were Hpylori-nogative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAsl/ml-positive. Antral mucosal tissues from H pylori-positive patients contained significantly （H pylori-positive NU patients： median 467 pg/mg/protein, range 53-2 499; Hpylori negative NU patients： median 104 pg/mg/protein, range 16-312, P〈0.0005） higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly （ulcer site： median 1 356 pcj/mg/protein, range 121-1 3730; antrum： median 761 pg/mg/protein, range 24-7 620, P〈0.005） higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the Hpylori-negativecontrols showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site （ulcer： r = 0.62,P〈0.0001; antrum： r = 0.61, P〈0.0001） in GU patients. RhIL-17 and Hpylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION： IL-17 may play an important role in the inflammatory response to Hpyloricolonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.

Management of Helicobacter pylori infection after gastric surgery

The Maastricht IV/Florence Consensus Report and the Second Asia-Pacific Consensus Guidelines strongly recommend eradication of Helicobacter pylori(H.pylori)in patients with previous gastric neoplasia who have undergone gastric surgery.However,the guidelines do not mention optimal timing,eradication regimens,diagnostic tools,and follow-up strategies for patients undergoing gastrectomy and do not indicate if eradication of H.pylori reduces the risk of marginal ulcer or stump cancer in the residual stomach after gastrectomy.The purpose of this review is to provide an update which may help physicians to properly manage H.pylori infection in patients who have undergone gastric surgery.This review focuses on(1)the microenvironment change in the stomach after gastrectomy;(2)the phenomenon of spontaneous clearance of H.pylori after gastrectomy;(3)the effects of H.pylori on gastric atrophy and intestinal metaplasia after gastrectomy;(4)incidence and clinical features of ulcers developing after gastrectomy;(5)does eradication of H.pylori reduce the risk of gastric stump cancer in the residual stomach?(6)does eradication of H.pylori reduce the risk of secondary metachronous gastric cancer in the residual stomach?and(7)optimal timing and regimens for H.pylori eradication,diagnostic tools and follow-up strategies for patients undergoing gastrectomy.

Helicobacter pyloriin gastric corpus of patients 20 years after partial gastric resection

AIM:To determine the long-term prevalence of Helicobacter pylori(H pylori)gastritis in patients after partial gastric resection due to peptic ulcer,and to compare the severity of Hpylori-positive gastritis in the corpus mucosa between partial gastrectomy patients and matched controls. METHODS:Endoscopic biopsies were obtained from 57 patients after partial gastric resection for histological examination using hematoxylin/eosin and Warthin-Starry staining.Gastritis was graded according to the updated Sydney system.Severity of corpus gastritis was compared between Hpylori-positive partial gastrectomy patients and Hpylori-positive duodenal ulcer patients matched for age and gender. RESULTS:In partial gastrectomy patients,surgery was performed 20 years(median)prior to evaluation.In 25 patients(43.8%)Hpyloriwas detected histologically in the gastric remnant.Gastric atrophy was more common in H pylori-positive compared to H pylori-negative partial gastrectomy patients(P<0.05).The severity of corpus gastritis was significantly lower in Hpylori-positive partial gastrectomy patients compared to duodenal ulcer patients (P<0.01).There were no significant differences in the activity of gastritis,atrophy and intestinal metaplasia between the two groups. CONCLUSION:The long-term prevalence of Hpylorigastritis in the gastric corpus of patients who underwent partial gastric resection due to peptic ulcer disease is comparable to the general population.The expression of Hpylorigastritis in the gastric remnant does not resemble the gastric cancer phenotype.

GC/MS-based differential metabolic profiling of human peptic ulcer disease to study Helicobacter pylori-induced metabolic perturbations

Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H.pylori-induced pathogenicity.The rationale of the study is to explore the underlying distinct metabolic mechanisms of H.pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry.GC/MS-based analytical method was used to compare metabolic profiles of healthy controls(N=20)and peptic ulcer patients(N=45).Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers.A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs.healthy gut tissues,among which 16 metabolites are being proposed to be diagnostic markers of Human PUD.Perturbations related to amino acids,carbohydrates,fatty acids,organic acids,and sterol metabolism were significantly revealed during this differential metabolomic profiling.Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.

Accuracy of Helicobacter pylori serology in two peptic ulcer populations and in healthy controls

AIM： To estimate the test characteristics of Heli- cobacter pylori （H pylori） serology and of C14-urea breath test （C14-UBT） in two different peptic ulcer populations and in community controls. Second, the aim was to explore the association between the level of Hpylori IgG antibodies and severity of inflammation as to active peptic ulceration in the same populations. METHODS： Vagotomized （n = 83）, medically treated peptic ulcer patients （n = 73） and one reference group of community controls （n = 88） were gastroscoped. H pylori status was determined by histology, bacterial growth, C14-UBT and serology. Based on the updated Sydney System, cumulative scores from biopsies from the prepyloruos, incisura angularis, corpus and fundus were calculated. RESULTS： The prevalence of Hpylori infection varied from 70% to 79%. The C14-UBT had high accuracy compared to the serology test. The sensitivity of the serology test was good, but the specificity was low （41%-71%）. The association between H pylori IgG antibodies and scores of gastric mucosal inflammation and current or previous peptic ulcer were weak. CONCLUSION： The accuracy of CI4-UBT to diagnose Hpylori infection was good, and the clinical utility of a negative H pylori serology test was substantial, while the gain in clinical information of a positive test was meagre. Positive H pylori titres could not distinguish between subjects with or those without active peptic ulceration.

To be or not to be:The host genetic factor and beyond in Helicobacter pylori mediated gastro-duodenal diseases

Helicobacter pylori(H.pylori)have long been associated with a spectrum of disease outcomes in the gastroduodenal system.Heterogeneity in bacterial virulence factors or strains is not enough to explain the divergent disease phenotypes manifested by the infection.This review focuses on host genetic factors that are involved during infection and eventually are thought to influence the disease phenotype.We have summarizedthe different host genes that have been investigated for association studies in H.pylori mediated duodenal ulcer or gastric cancer.We discuss that as the bacteria co-evolved with the host;these host gene also show much variation across different ethnic population.We illustrate the allelic distribution of interleukin-1B,across different population which is one of the most popular candidate gene studied with respect to H.pylori infections.Further,we highlight that several polymorphisms in the pathway gene can by itself or collectively affect the acid secretion pathway axis(gastrin:somatostatin)thereby resulting in a spectrum of disease

Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, antioxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori(H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake.

Polymorphism of -765G > C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection:A study from northern India

AIM: To investigate -765G > C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and non- ulcer dyspepsia (NUD). METHODS: We enrolled 348 adult patients (62 gastric adenocarcinoma, 45 PUD and 241 NUD) undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests (RUT, culture, histopathology and PCR) were positive. Genotyping for -765G > C polymorphism of COX-2 was performed by PCR-RFLP analysis. RESULTS: Frequency of C carrier had significantassociation with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P < 0.001, odds ratio (OR) 8.20; 95% confidence interval (95% CI), 4.08-16.47] and PUD (77.4% vs 31.1%, P < 0.001; OR 8.04; 95% CI, 3.25-19.90). Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with (OR 7.83; 95% CI 3.09-19.85) and without H pylori infection (OR 7.06; 95% CI, 2.61-19.09). Patients with C carrier and H pylori infection had significant risk for the development of PUD (P < 0.001; OR 5.65; 95% CI, 2.07-15.34). CONCLUSION: -765G > C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.

Clinical proteomics identifies potential biomarkers in Helicobacter pylori for gastrointestinal diseases

The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell&#x02019;s translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.