Helicobacter pylori and colorectal neoplasia: Is there a causal link?

Ever since Helicobacter pylori(H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from casecontrol and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori /H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation.     

Helicobacter pylori infection and inflammatory bowel disease: Is there a link?

Helicobacter pylori(H.pylori)infection is one of the most widely spread infectious diseases in humans.It can cause chronic gastritis,peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders.H.pylori elicit a chronic systemic inflammatory response which,under certain conditions,may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases.Although the pathogenesis of inflammatory bowel disease(IBD)is unknown,it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible.Several bacterial and viral agents have been implicated in the aetiology of IBD.In theory,H.pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways.Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations.However,the epidemiological data fail to support this association.Infact,various studies indicate that the prevalence of H.pylori infection is low in patients with IBD,suggesting a protective role for this infection in the development of IBD.In this report,we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H.pylori infection and IBD.     

Is nonulcer dyspepsia related to Helicobacter pylori infection?

Dyspepsia, defined as pain or discomfort centered in the upper abdomen, is a common clinical problem. A variety of underlying disease states may result in dyspepsia, but commonly, diagnostic investigation will show no identifiable pathology, and the patient is diagnosed with nonulcer dyspepsia. Numerous hypothesis have been suggested as to the cause of symptoms in patients with nonulcer dyspepsia, including perturbations of gastroduodenal motility, hypersensitivity to physiologic stimuli including acid, and the effect(s) of infection within the gastric mucosa by Helicobacter pylori. Some epidemiological studies have suggested that patients with nonulcer dyspepsia may have a slightly higher prevalence of H. pylori infection. However, association does not prove causation. Causation of nonulcer dyspepsia by H. pylori could best be documented by resolution of symptoms following eradication of the infection. Early intervention studies indicated that there was a beneficial effect on symptoms of nonulcer dyspepsia with H. pylori eradication, but most of these studies had serious methodological flaws. In the last few years there have been a number of well-designed studies investigating the effect of H. pylori eradication on symptoms in patients with nonulcer dyspepsia. The results of these studies are inconsistent, but suggest that there is little, if any benefit from treatment. This case-based article on nonulcer dyspepsia discusses these studies in detail and provides a possible explanation for the differences in outcomes.     

Respiratory diseases and Helicobacter pylori infection: is there a link?

Recent studies suggest an epidemiological association between Helicobacter pylori infection and several extra-gastroduodenal pathologies, including cardiovascular, rheumatic, skin and liver diseases. The observed associations might be explained by a role of H. pylori infection in the pathogenesis of certain extra-digestive disorders, as a variety of inflammatory mediators are activated by H. pylori infection. The present review summarizes the current literature, including our own studies, concerning the association between respiratory diseases and H. pylori infection. A small number of epidemiological and serologic case-control studies suggest that patients with chronic obstructive pulmonary disease have an increased seroprevalence of H. pylori. A frequent coexistence of bronchiectasis and H. pylori infection has also been found. Moreover, recent studies have shown an increased prevalence of H. pylori infection in patients with pulmonary tuberculosis and in those with lung cancer. On the other hand, bronchial asthma does not seem to be related to H. pylori infection. At present, there is no definite proof of a causal relationship between H. pylori and respiratory diseases. The primary evidence rests on case-control studies, concerning relatively small numbers of patients. Future studies should be large enough for moderate-sized effects to be assessed or registered reliably. The activation of inflammatory mediators by H. pylori infection might be the pathogenetic mechanism underlying the observed associations. Therefore, the role of genetic predisposition of the infected host, the presence of strain-specific virulence factors and the serum concentration of proinflammatory markers in H. pylori-infected patients with respiratory diseases need further evaluation.     

Helicobacter pylori infection and endocrine disorders： Is there a link？

Helicobacter pylori （H pylori） infection is a leading world-wide infectious disease as it affects more than half of the world population and causes chronic gastritis, peptic ulcer disease and gastric malignancies. The infection elicits a chronic cellular inflammatory response in the gastric mucosa. However, the effects of this local inflammation may not be confined solely to the digestive tract but may spread to involve extraintestinal tissues and/or organs. Indeed, H pylori infection has been epidemiologically linked to extra-digestive conditions and diseases. In this context, it has been speculated that Hpylori infection may be responsible for various endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus, dyslipidemia, obesity, osteoporosis and primary hyperparathyroidism. This is a review of the relationship between H pylori infection and these endocrine disorders.     

Helicobacter pylori infection and atopic diseases: Is there a relationship? A systematic review and meta-analysis

AIM: To review and conduct a meta-analysis of the existing literature on the relationship between Helicobacter pylori (H. pylori), atopy and allergic diseases.METHODS: Studies published in English assessing the prevalence of atopy and/or allergic diseases in patients with H. pylori infection and the prevalence of H. pylori infection in patients with atopy and/or allergic diseases were identified through a MEDLINE search (1950-2014). Random-effect model was used for the meta-analysis.RESULTS: Pooled results of case-control studies showed a significant inverse association of H. pylori infection with atopy/allergic disease or with exclusively atopy, but not with allergic disease, whereas pooled results of cross-sectional studies showed only a significant association between allergic disease and H. pylori infection.CONCLUSION: There is some evidence of an inverse association between atopy/allergic diseases and H. pylori infection, although further studied are needed.     

Helicobacter pylori infection: protection against Barrett's mucosa and neoplasia?

BACKGROUND: Since Helicobacter pylori (Hp) infection provokes intestinal and gastric metaplasia, the question arises whether the specialized metaplasia (Barrett's mucosa (BM)) and dysplasia or carcinoma in Barrett's epithelium seen in gastro-oesophageal reflux disease (GORD) might not also be correlated with Hp infection, or whether the latter offers protection against Barrett's oesophagus and Barrett's adenocarcinoma. PATIENTS: Gastric and oesophageal biopsies obtained from a total of 2,201 patients were analysed retrospectively. 297 of these patients had GORD (age 53.5 +/- 13.4 years; m:f ratio 2.1:1), 1,192 patients had BM (age 62.8 +/- 14.6 years; m:f 2.3:1) with or without neoplasia. 1,054 of these patients were diagnosed as having BM alone, 138 patients having BM neoplasia (high-grade dysplasia or adenocarcinoma). Patients with BM and low-grade dysplasia were excluded from this study because of the uncertainty in differentiating low-grade dysplasia from regenerative epithelium. A total of 712 patients with non-ulcer dyspepsia (NUD; average age 40.0 +/- 16.1 years; m:f 0.3:1) served as a control group. RESULTS: The percentage of Hp infection did not differ between patients with GORD with (53.3%)/without BM (51.4%) and neoplasia (47.8%), but is statistically significantly lower than in patients with NUD (65.7%). CONCLUSION: Our analysis shows that patients with GORD and Hp infection have no increased risk for the development of BM or neoplasia in BM. Since Hp infection is significantly less frequent in GORD than in NUD patients, a protective effect of the Hp infection is a possibility worth discussing.     

Helicobacter pylori infection and diabetes: Is it a myth or fact?

Helicobacter pylori(H.pylori)is one of the most common human bacterial pathogens,and infection causes a wide array of gastric disorders,including simple gastritis,peptic ulcers and gastric malignancies.Gastrointestinal inflammation caused by H.pylori can influence the absorption of glucose and lipids,which are also abnormal in diabetes mellitus.Type 2 diabetes mellitus(T2DM),formerly known as non-insulin-dependent diabetes mellitus or adult-onset diabetes,is a metabolic disorder that is characterized by high levels of blood glucose resulting from insulin resistance and relative insulin deficiency.It is an emerging pandemic and is rapidly becoming a serious threat to public health.Emerging data now indicate a strong relationship between H.pylori infection and the incidence of T2DM.The mechanisms underlying the pathogenesis of diabetes are complex,involving insulin resistance,chronic inflammation,insulin secretion deficiency as a result of pancreasβ-cell dysfunction,glucotoxicity,and lipotoxicity.H.pylori infection is known to be involved in the pathogenesis of insulin resistance,and the growing awareness of its role in diabetes is important for the early detection of glucose dysregulation and prevention of T2DM in high-risk communities.This review probes the possible relationship between H.pylori and diabetes according to epidemiological surveys and discusses putative mechanisms underlying this correlation.     

Carditis: all Helicobacter pylori or is there a role for gastro-oesophageal reflux?

BACKGROUND: Recent epidemiological studies have reported a threefold increase in the incidence of adenocarcinoma of the lower oesophagus and gastro-oesophageal junction (cardia). There are conflicting reports available implicating both gastro-oesophageal reflux disease and Helicobacter pylori infection in the aetiology of carditis and cardia intestinal metaplasia, despite strong evidence to show that these two conditions are, if anything, inversely related. We aimed to determine the prevalence of carditis and cardia intestinal metaplasia in dyspeptic subjects and also their association with H. pylori infection and gastro-oesophageal reflux disease. METHOD: Histological samples from the gastric cardia were obtained from dyspeptic subjects. H. pylori status was assessed based on histological, microbiological and rapid urease testing. Gastro-oesophageal disease was diagnosed on the basis of histological evidence and/or erosive oesophagitis. Patient demographics were recorded. Cardia intestinal metaplasia (CIM), when present, was subgrouped as complete or incomplete. RESULTS: Overall, 276 subjects were enrolled; 163 (59%) had carditis and 36 (13%) CIM. H. pylori infection and gastro-oesophageal reflux disease occurred in 64 (23%) and 150 (54%), respectively. H. pylori infection was strongly associated with carditis and CIM (P<0.001 and P<0.01). Older age and male gender were also associated with inflammation and intestinal metaplasia of the cardia. Gastro-oesophageal reflux was not associated with either entity. CONCLUSION: Carditis and CIM occur frequently. Both conditions are strongly associated with H. pylori infection, older age and male gender. There was no association with gastro-oesophageal reflux disease.