Helicobacter pylori and extragastric diseases: A review

Helicobacter pylori(H. pylori) infection is very common and affects approximately half of the world population. It causes gastric diseases, but some authors have reported an association of H. pylori infection with other systemic manifestations beginning in 1994. The list of potential effects of H. pylori outside the stomach includes a number of extragastric manifestations and we focused on neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, allergic, and hepatobiliary diseases. This review discusses these important reported manifestations that are not related to the gastrointestinal tract.

Helicobacter pylori infection: Beyond gastric manifestations

Helicobacter pylori(H.pylori)is a bacterium that infects more than a half of world’s population.Although it is mainly related to the development of gastroduodenal diseases,several studies have shown that such infection may also influence the development and severity of various extragastric diseases.According to the current evidence,whereas this bacterium is a risk factor for some of these manifestations,it might play a protective role in other pathological conditions.In that context,when considered the gastrointestinal tract,H.pylori positivity have been related to Inflammatory Bowel Disease,Gastroesophageal Reflux Disease,Non-Alcoholic Fatty Liver Disease,Hepatic Carcinoma,Cholelithiasis,and Cholecystitis.Moreover,lower serum levels of iron and vitamin B12 have been found in patients with H.pylori infection,leading to the emergence of anemias in a portion of them.With regards to neurological manifestations,a growing number of studies have associated that bacterium with multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,and Guillain-Barrésyndrome.Interestingly,the risk of developing cardiovascular disorders,such as atherosclerosis,is also influenced by the infection.Besides that,the H.pylori-associated inflammation may also lead to increased insulin resistance,leading to a higher risk of diabetes mellitus among infected individuals.Finally,the occurrence of dermatological and ophthalmic disorders have also been related to that microorganism.In this sense,this minireview aims to gather the main studies associating H.pylori infection with extragastric conditions,and also to explore the main mechanisms that may explain the role of H.pylori in those diseases.

Helicobacter pylori in human health and disease:Mechanisms for local gastric and systemic effects

Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.

Molecular mimicry in Helicobacter pylori infections

Gram-negative bacteria Helicobacter pylori(H. pylori) colonize gastric mucosa in humans and increase the risk of serious diseases such as gastric and duodenal ulcers, stomach cancers and mucosa associated lymphoid tissue lymphoma. The role of H. pylori infection in the pathogenesis of several extragastric diseases has been suggested including immune thrombocytopenic purpura, iron deficiency anemia, vitamin D deficiency, cardiovascular diseases,diabetes mellitus and dermatological disorders. Also neurological diseases and even lung cancer have attracted researchers concern. The relation between H. pylori infection and a growth retardation in children has also been suggested. Many mechanisms of molecular mimicry between H. pylori and the host have been proposed as a pathogen strategy to manipulate the immune system of the host in order to remain unrecognized and avoid eradication. A lot of effort has been put into the demonstration of homologous sequences between H. pylori and host compounds. However, knowledge about how often autoantibodies or autoreactive T lymphocytes induced during H. pylori infections cause pathological disorders is insufficient. This review provides data on H. pylori antigenic mimicry and possible deleterious effects due to the induction of immune response to the components common to these bacteria and the host.

Helicobacter pylori infection in Mongolian gerbils does not initiate hematological diseases

AIM:To investigate whether Helicobacter pylori(H.pylori)infection contributes to idiopathic thrombocytopenic purpura(ITP)or iron-deficiency anemia(IDA)onset in gerbils.METHODS:A total of 135 Mongolian gerbils were randomly divided into two groups:an H.pylori infection group and a control group.Both groups were fed the same diet and the same amount of food.Each group was then divided into three subgroups,which were sacrificed at 6,12,or 18 mo for analysis.At each time point,arterial blood was collected from the abdominal aorta and a complete blood cell count was analyzed in the clinical laboratory in the First Affiliated Hospital of Nanchang University.RESULTS:There were no significant differences in platelet counts(938.00±270.27/L vs 962.95±162.56×109/L),red blood cell counts(8.11±1.25/L vs 8.44±1.48×1012/L),or hemoglobin levels(136.9±8.76g/L vs 123.21±18.42 g/L)between the control and the H.pylori groups,respectively,at 18 mo.With the exception of the mean corpuscular volume(MCV),all other indicators,including white blood cell counts,hematocrit,mean corpuscular hemoglobin,mean corpuscular hemoglobin concentration,red blood cell distribution width,mean platelet volume,platelet distribution width,lymphocyte count,and lymphocyte count percentage,showed no significant differences between the control and H.pylori infection groups at each time point.The MCV in the H.pylori infection group(52.32f/L±2.86 f/L)was significantly lower than the control group(55.63±1.89 f/L)at 18 mo(P=0.005),though no significant differences were observed at 6(54.40±2.44 f/L vs 53.30±1.86 f/L)or 12 mo(53.73±2.31f/L vs 54.80±3.34 f/L).CONCLUSION:A single H.pylori infection is insufficient to cause onset of ITP or IDA and other factors may be required for disease onset.

Helicobacter pylori infection and asthma:Is there a direct or an inverse association?A meta-analysis

AIM:To analyze the consistency of a potential involvement of the bacterium infection in the asthma disease. METHODS:A systematic literature search of the terms "Helicobacter pylori "(H. pylori) associated to "asthma" using PubM ed,Scopus and the Cochrane Library Central was performed. Reference lists from published articles were also employed. Titles of these publications and their abstracts were scanned in order to eliminate duplicates and irrelevant articles. The criteria of inclusion of the studies were:Original studies; the H. pylori diagnostic method has been declared; all ranges of age have been included in our study; a definitive diagnosis of asthma has been reported.RESULTS:We selected 14 articles in which the association between the two conditions was addressed. In 7 studies the prevalence of H. pylori infection in the asthma population and in the control population was made explicit. There was heterogeneity between the studies(Cohran's Q = 0.02). The H. pylori infection in the asthma population resulted 33.6%(518 of 1542),while in the control population resulted 37.6%(2746 of 7310)(relative risk of H. pylori infection in the asthma population = 0.87,95%CI:0.72-1.05,P = 0.015,random effects model). Instead,considering the morevirulent strains,the majority of studies showed an inverse relationship between the prevalence of H. pylori infection and asthma.CONCLUSION:In our meta-analysis the prevalence of H. pylori infection in the asthma population resulted not statistically significant lower than in control population(P = 0.15). Instead,considering the more virulent strains,the majority of studies showed an inverse relationship between the prevalence of H. pylori infection and asthma.