Helicobacter pylori might be a potential therapeutic target in epilepsy

Brain-gut axis in the pathogenesis ofHelicobacter pyloriinfection

“…As a gastric mucosa-colonizing microorganism, H. pylori may contribute to the bidirectional nature of the brain-gut axis as evidenced by: (1) the overlapping of upper and lower digestive tract functional symptoms in H. pylori infected patients [18,[41][42][43] and the effect of H. pylori infection on IBS symptoms [43] (but see Breckan et al [44] ) and pancreatic juice secretion [45] ; (2) the protection against IBD appearance by H. pylori infection [17,46] resulting from changes induced in brain-gut axis function (neuroendocrine-immune crosstalk) [6,15,21,22,26,47,48] ; (3) the association of H. pylori infection with ANS-related extra-digestive diseases, such as atherosclerosis or cardiac arrhythmia [3,35] ; (4) the improved physical and psychological health-related quality of life and sexual relationships after digestive tract symptom alleviation and H. pylori eradication [49,50] ; (5) the proposed association between H. pylori infection and the development of axonal type Guillain-Barré neuropathy, multiple sclerosis and epilepsy [51][52][53] , and case reports of gastric MALT lymphoma followed by primary CNS lymphoma [54] ; and (6) the modulation of ANS balance by H. pylori infection [35] . Furthermore, H. pylori can potentially regulate esophageal motility [55] , gastric emptying, gastric accommodation of ingested food, gastric acid secretion, mucosal blood flow, hypersensitivity to chemoand mechano-stimulants [56] , food intake [6,19] , digestive tract endocrine and immune functions and the composition of gut microbiota [6,18,21,22] , by influencing the release of various neurotransmitters, including acetylocholine (vagal nerve, parasympathetic part), noradrenaline, adrenaline and sympathetic dopamine, as well as the neuropeptides leptin, ghrelin, calcitonin gene-related peptide (CGRP), nitric oxide, neuropep...…”

“…Whereas bloodbrain barrier disruption may be secondary to the effects of H. pylori-induced inflammatory mediators, it can lead to increased brain vessel permeability for immunomediators, non-specific antibodies, AQP4-specific antibodies and inflammatory cells (e.g., lymphocytes), which can evoke many pathological processes in the CNS, including demyelination, local edema and neuroinflammation. These processes are recognized as important for associations between H. pylori infection and the pathogenesis of demyelination, multiple sclerosis and neuromyelitis optica [51,52,79] .…”

Meta-analysis of Association between Helicobacter pylori Infection and Epilepsy

“…Bartolomei, et al [18] found that detection of anti-GM1 antibodies could allow identification of patients with partial epilepsy associated with an autoimmune response. H. pylori could indirectly influence the brain function due to the release of multiple cytokines such as IL-1,IL-6,TNF-α,which involved in the blood-brain barrier (BBB) disruption and pathogenesis of neuronal inflammatory damage in epilepsy [19,20]. Kountouras,et al [20] have hypothesized that H. pylori might be a potential therapeutic target in epilepsy.…”

Multiple sclerosis and seizures: possible role ofHelicobacter pylori

“…Moreover, using histology, the practical gold standard for current Hp ‐I diagnosis, we showed a strong association between Hp ‐I and MS in a Greek cohort [3]. In this respect, we proposed that Hp ‐I, by inducing pro‐inflammatory cytokine production and BBB disruption [4], may lead to neuroinflammation and neuronal damage in epilepsy, thereby triggering seizures’ induction and epilepsy progression [5].…”

“…Specifically, a series of factors have been implicated in inducing BBB disruption, including inflammatory mediators (e.g. cytokines and chemokines induced by Hp ‐I) and oxidative stress [5,6]. Hp could indirectly affect the brain through the release of numerous pro‐inflammatory cytokines, such as IL‐1b, IL‐18, IFN‐γ [7] mentioned by the authors, or tumor necrosis factor (TNF)‐α acting at a distance.…”