Brain-gut axis in the pathogenesis of Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches.

Exercise-provoked esophageal motility disorder in patients with recurrent chest pain

AIM:To investigate the relationship between exerciseprovoked esophageal motility disorders and the prognosis for patients with chest pain.METHODS:The study involved 63 subjects with recurrent angina-like chest pain non-responsive to empirical therapy with proton pump inhibitor(PPI).In all,a coronary artery angiography,panendoscopy,24-h esophageal pH-metry and manometry,as well as a treadmill stress test with simultaneous esophageal pH-metry and manometry monitoring,were performed.Thirtyfive subjects had no significant coronary artery lesions,and 28 had more than 50% coronary artery narrowing.In patients with hypertensive esophageal motility disorders,a calcium antagonist was recommended.The average follow-up period was 977 ± 249 d.RESULTS:The prevalence of esophageal disorders,such as gastroesophageal reflux or diffuse esophageal spasm,was similar in patients both with and without significant coronary artery narrowing.Exercise prompted esophageal motility disorders,such as a decrease in the percentage of peristaltic and effective contractions and their amplitude,as well as an increase in the percentage of simultaneous and non-effective contractions.In 14(22%) patients the percentage of simultaneous contractions during the treadmill stress test exceeded the value of 55%.Using Kaplan-Meier analysis and the proportional hazard Cox regression model,it was shown that the administration of a calcium channel antagonist in patients with such an esophageal motility disorder significantly decreased the risk of hospitalization as a result of a suspicion of acute coronary syndrome after the 2.7-year follow-up period.CONCLUSION:In patients with chest pain non-responsive to PPIs,a diagnosis of exercise-provoked esophageal spasm may have the effect of lowering the risk of the next hospitalization.

Exertional esophageal pH-metry and manometry in recurrent chest pain

AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-like chest pain, non-respon- sive to therapy with proton pump inhibitors. Sixty-five (59%) had non-obstructive lesions in coronary artery angiography, and in 46 (41%) significant coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry and manometry, and treadmill stress tests with simultaneous esophageal pH-metry and manometry monitoring were performed. During a 24-h examination the percentage of spontaneous chest pain (sCP) episodes associated with acid reflux or dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid gastroesophageal reflux (GER) were classified as having GER-related sCP. The remaining symptomatic individuals were determined as having non-GER-related sCP. During the stress test, the occurrence of chest pain, episodes of esophageal acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of simultaneous contractions (exercise-provoked esophageal spasm or EPES) were noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal function monitoring. Eleven of these (16%) were classified as having GER-related sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest pain during a stress test occurred in 13/111 (12%) subjects. In order to compare the clinical usefulness of 24-h esophageal function monitoring and its examination limited only to the treadmill stress test, the standard parameters of diagnostic test evaluation were determined. The occurrence of GER- related or non-GER-related sCP was assumed as a "gold standard". Afterwards, accuracy, sensitivity and specificity were calculated. These parameters expressed a prediction of GER-related or non-GER-related sCP occurrence by the presence of chest pain, esophageal acidification and EPES. Accuracy, sensitivity and specificity of chest pain during the stress test predicting any sCP occurrence were 28%, 35% and 80%, respectively, predicting GER- related sCP were 42%, 0% and 83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%, respectively. Similar values were obtained for exercise-related acidification with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and 92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%, respectively). CONCLUSION: The presence of chest pain, esophageal acidification and EPES had greater than 80% specificity to exclude the GER-related and non-GER-related causes of recurrent chest pain.

Coexistence of proangiogenic potential and increased MMP-9, TIMP-1, and TIMP-2 levels in the plasma of patients with critical limb ischemia

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.