The trimebutine effect on Helicobacter pylori-related gastrointestinal tract and brain disorders: A hypothesis.

The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a non-commensal symbiotic gastrointestinal pathogen) infection and its related metabolic syndrome have been implicated in the pathogenesis of gastrointestinal tract and central nervous system disorders, thus medications affecting the nervous system - gastrointestinal tract may shape the potential of Helicobacter pylori infection to trigger these pathologies. Helicobacter pylori associated metabolic syndrome, by impairing gut motility and promoting bacterial overgrowth and translocation, might lead to brain pathologies. Trimebutine maleate is a prokinetic drug that hastens gastric emptying, by inducing the release of gastrointestinal agents such as motilin and gastrin. Likewise, it appears to protect against inflammatory signal pathways, involved in inflammatory disorders including brain pathologies. Trimebutine maleate also acts as an antimicrobial agent and exerts opioid agonist effect. This study aimed to investigate a hypothesis regarding the recent advances in exploring the potential role of gastrointestinal tract microbiota dysbiosis-related metabolic syndrome and Helicobacter pylori in the pathogenesis of gastrointestinal tract and brain diseases. We hereby proposed a possible neuroprotective role for trimebutine maleate by altering the dynamics of the gut-brain axis interaction, thus suggesting an additional effect of trimebutine maleate on Helicobacter pylori eradication regimens against these pathologies.

Alzheimer's disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement.

Background: Alzheimer disease (AD) is a leading cause of global burden with great impact on societies. Although research is working intensively on promising therapy, the problem remains up-to-date. Among the various proposed hypotheses regarding causality and therapy, emerging evidence supports the hypothesis that gastrointestinal microbiota through the so-called 'gut-brain axis' interacts with immune system and brain and shape the balance between homeostasis and disease; the involvement of gastrointestinal microbiota in the pathophysiology of AD is less defined, even though the role of 'gut-brain axis' has been well verified for other neurodegenerative conditions.Methods: We performed a systematic review of PubMed/MEDLINE database from 1st January 1990 to 17th October 2018, to investigate the accessible literature regarding possible association between AD and gastrointestinal microbiota. Inclusion criteria were available full text in English language, original clinical papers implicating AD patients and any sort of gastrointestinal microbiota.Results: Through our query, an initial number of 241 papers has been identified. After removing duplicates and through an additional manual search, twenty-four papers met our inclusion criteria. The great majority of eligible publications supported a possible connection between AD and gastrointestinal microbiota. The most common investigated microorganism was Helicobacter pylori.Conclusion: Our own systematic review, showed a possible association between AD and gastrointestinal microbiota mainly including Helicobacter pylori, and thus further research is required for substantiation of causality as well as for the establishment of promising novel therapies.

Helicobacter pylori infection as a potential risk factor for multiple sclerosis.

Helicobacter pylori infection (Hp-I) has been associated with a wide spectrum of gastrointestinal and extra-digestive manifestations, including neurodegenerative diseases. Contradictory data have been published on Hp-I and multiple sclerosis (MS) association, with studies mainly using serology for Hp-I detection that cannot distinguish between active and past infections. We herein hypothesize that humoral and cellular immune responses induced by active Hp-I, beyond damaging locally the gastric mucosa, they may shape the character of systemic autoimmune responses, contributing to MS pathogenesis. To investigate our hypothesis, active Hp-I has been diagnosed in two small MS Greek cohorts by using primarily gastric mucosa histology. A higher prevalence of active Hp-I was documented in MS patients vs. controls (86.4 vs. 50%, P = 0.002)accompanied by exclusive existence of duodenal ulcer and autoimmune diseases with endoscopic and histological findings of chronic active gastritis for the MS group. Our preliminary data suggested that active Hp-Iunlike other studies, may not protect, but contribute to MS and we proposed possibleHp-relating mechanisms involved in MS pathophysiology, that merit further evaluation.

Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis.

Background: Glaucoma is the second most common cause of blindness worldwide affecting almost 70 million individuals. Helicobacter pylori (H. pylori) is a widespread pathogen with systematic pathogenicity. This meta-analysis aimed to estimate the contradictory data regarding a potential association between active H. pylori infection and glaucoma. Materials and Methods: A research in MEDLINE/PubMed and Google Scholar was conducted and original studies investigating the relationship between H. pylori infection and glaucoma were included. Analysis was performed with random effects model. The main outcome was the odds ratio (OR) with 95% confidence intervals (CI) of H. pylori infection as a risk factor for glaucoma. A parallel analysis studied the role of active infection as indicated by histology and the titer of anti-H. pylori antibodies. For the anti-H. pylori antibody titers, weighted mean differences (WMD) were estimated between patients and controls. Results: Fifteen studies were included, with 2664 participants (872 patients with glaucoma and 1792 controls), divided into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudo-exfoliation glaucoma (PEG). The association between H. pylori infection and overall glaucoma was significant (OR = 2.08, CI 95% 1.48-2.93) with moderate heterogeneity (I2 = 61.54%). After stratification by glaucoma subtype, heterogeneity was eliminated in the NTG subgroup. Studies with healthy controls, and controls with anemia yielded very low or no heterogeneity, respectively. Gastric biopsy to document active H. pylori infection yielded the highest OR (5.4, CI: 3.17-9.2, p < 0.001) and null heterogeneity. For anti-H. pylori antibody titers, there was a significant difference in WMD between patients and controls (WMD 15.98 IU/mL; 95% CI: 4.09-27.87; p = 0.008); values were greater in glaucoma patients, with high heterogeneity (I2: 93.8%). Meta-regression analysis showed that mean age had a significant impact on glaucoma (p = 0.037). Conclusions: Active H. pylori infection may be associated with glaucoma with null heterogeneity, as, beyond histology, quantified by anti-H. pylori titers and increases with age.

Rodent models of obesity.

Obese or overweight people exceed one-third of the global population and obesity along with diabetes mellitus consist basic components of metabolic syndrome, both of which are known cardio-cerebrovascular risk factors with detrimental consequences. These data signify the pandemic character of obesity and the necessity for effective treatments. Substantial advances have been accomplished in preclinical research of obesity by using animal models, which mimic the human disease. In particular, rodent models have been widely used for many decades with success for the elucidation of the pathophysiology of obesity, since they share physiological and genetic components with humans and appear advantageous in their husbandry. The most representative rodents include the laboratory mouse and rat. Within this review, we attempted to consolidate the most widely used mice and rat models of obesity and highlight their strengths as well as weaknesses in a critical way. Our aim was to bridge the gap between laboratory facilities and patient's bed and help the researcher find the appropriate animal model for his/her obesity research. This tactful selection of the appropriate model of obesity may offer more translational derived results. In this regard, we included, the main diet induced models, the chemical/mechanical ones, as well as a selection of monogenic or polygenic models.

Helicobacter pylori eradication regimens in an antibiotic high-resistance European area: A cost-effectiveness analysis.

INTRODUCTION: Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis. AIM: This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period. MATERIALS AND METHODS: Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations. RESULTS: Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively). DISCUSSION: This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I.

Impact of nitric oxide's bidirectional role on glaucoma: focus on Helicobacter pylori-related nitrosative stress.

Nitric oxide (NO), a small molecule generated ubiquitously, targets a plethora of tissues to regulate both physiological and pathophysiological functions. NO overproduction, stimulated by microenvironmental conditions, is the main component that dysregulates the tight balance between its beneficial and damaging roles in ocular homeostasis. Considering the protective functions of NO against glaucoma, its endogenous release facilitates aqueous humor drainage and regulates ocular blood flow, maintaining a normal intraocular pressure. NO overproduction generates free radicals, such as peroxynitrite, which induce a vicious circle of vascular disharmony and dysregulation, transient ischemia, nitrosative stress, neuronal degeneration, and permanent glaucomatic injury. Helicobacter pylori (Hp) is considered a burdening factor of glaucoma. NO overproduction and possible systematic dispersion in Hp infection (Hp-I) could suggest a potential pathophysiological bridge between these conditions. In this review, we aim to elucidate the role of NO in glaucoma with respect to Hp-I, with the aim to stimulate further studies.

The impact of selective serotonin receptor inhibitors on post-endoscopic sphincterotomy bleeding, alone or with concurrent aspirin or nonsteroidal anti-inflammatory drugs.

BACKGROUND: Observational studies have shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs). We retrospectively investigated the impact of SSRIs, alone or combined with aspirin (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs), on the incidence of post-endoscopic sphincterotomy (post-ES) bleeding. METHODS: A total of 3058 patients were included. Of these, 457 patients received SSRIs, alone or plus ASA or NSAIDs, until the day of ES (SSRIs group), while 2659 patients (non SSRIs group) had never been on SSRIs (n=1925), though some had been on ASA (n=613) or NSAIDS (n=121). Patient assessment included indication for endoscopic retrograde cholangiopancreatography (ERCP), comorbid diseases, detailed drug history before and after ES, procedural details, and risk factors for post-ES bleeding. Primary outcome was defined as the incidence, type and severity of post-ES bleeding. RESULTS: There was no statistical difference in age, sex, indication for ERCP, comorbid diseases, technical characteristics or results of therapeutic ERCP between the 2 groups. The incidence of post-ES bleeding was 3.9% in the SSRIs group and 3% in the non SSRIs group, a difference not statistically significant (P=0.754). Likewise, there was no difference in type (P=0.145) or severity of bleeding (P=0.754) between the 2 groups. Multivariate analysis showed the precut technique as the only independent risk factor for post ES hemorrhage (odds ratio 2.56, 95% confidence interval 1.23-3.63; P=0.001). CONCLUSION: This study found that SSRIs, alone or combined with ASA or NSAIDs, had no influence on the incidence or the severity of post-ES bleeding.

Molecular Links Between Alzheimer's Disease and Gastrointestinal Microbiota: Emphasis on Helicobacter pylori Infection Involvement.

Alzheimer's disease (AD) is a neurodegenerative disease and the main form of dementia, characterized by progressive cognitive decline and detrimental consequences in both personal-family and global level. Within this narrative review, we provide recent molecular aspects of Tau, a microtubule AD-associated protein, as well as amyloid beta, involved in AD pathophysiology. Moreover, we provide additional emerging data from basic research as well as clinical studies indicating an implicating role of gastrointestinal microbiota (GI-M), including Helicobacter pylori infection (Hp-I), in AD pathophysiology. Likewise, we identified through a molecular prism the current evidence of AD pathogenesis as well as its linkage with GI-M and emphasizing the role of Hp-I. All in all, additional large-scale studies are required for the further clarification of AD pathophysiology and its connection with GI-M and Hp-I, so as novel therapies on molecular basis become available.

A perspective on risk factors for esophageal adenocarcinoma: emphasis on Helicobacter pylori infection.

Gastroesophageal reflux disease (GERD) and the increasing rate of its associated complications, including esophageal adenocarcinoma (EAC), has stimulated a plethora of studies attempting to evaluate provocative and protective factors. Helicobacter pylori (Hp) infection (Hp-I) was initially considered as a beneficial condition in GERD management based on rather limited data. Large-scale regional studies revealed an alternative approach, by suggesting a positive relationship between Hp-I and EAC development. Regarding pathophysiology, Hp-I induces gastric microbiota disturbances through hypochlorhydria and chronic inflammation, with a subsequent possible effect on the GERD-Barrett's esophagus (BE)-EAC cascade. Additionally, both direct effects on esophageal mucosa and indirect effects on known mechanisms of GERD, such as acid pocket and transient lower esophageal sphincter relaxation, remain to be elucidated. Hp contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase-2, and prostaglandins; Ki-67 is also expressed and represents an index of BE-related malignancy. Moreover, Hp-I is vigorously suggested as a risk factor for metabolic syndrome, which may be the link between Hp-I and EAC. Although further studies are necessary to establish a pathophysiologic risk between Hp-I and the GERD-BE-EAC sequence, the theory of Hp protection against GERD seems outdated.

Impact of occupational stress on irritable bowel syndrome pathophysiology and potential management in active duty noncombat Greek military personnel: a multicenter prospective survey.

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the gut-brain axis interaction disorders. It has global distribution with varying prevalence and particular financial and psychological consequences. IBS has been associated with stress and anxiety, conditions that are usually prevalent in the army. There are scarce data investigating the impact of IBS on noncombat active duty military without reports of Greek military or stress in the occupational environment. MATERIALS AND METHODS: The main exclusion criteria in our noncombat military multicenter prospective survey were gastrointestinal pathologies, malignancies, hematochezia, recent infections and antibiotics prescription, and pregnancy. Questionnaires included a synthesis of baseline information, lifestyle, and diet, psychological and stress-investigating scales and the IBS diagnosis checklist. Hospital Anxiety and Depression Scale and Rome IV criteria were utilized. RESULTS: Among 1605 participants included finally, the prevalence of IBS was 8% and 131 cases were identified. Women were more vulnerable to IBS, although male sex was prevalent at a ratio of 3.5 : 1 (male:female) in the entire sample. The mean age of all participants was 23.85 years; most of the IBS patients were older than thirty. Abnormal anxiety scores and high levels of occupational stress were related to an IBS diagnosis. DISCUSSION: This prospective multicenter survey showed, for the first time, the potential impact of occupational stress on IBS in active duty noncombat Greek Military personnel. The diagnosis of IBS by questionnaire is a quick, affordable way that can upgrade, by its management, the quality of life and relieve from the military burden. Our results are comparable with previous studies, although large-scale epidemiological studies are required for the confirmation of a possible causative relationship.