Impact of Helicobacter pylori and metabolic syndrome on mast cell activation-related pathophysiology and neurodegeneration.

Both Helicobacter pylori (H. pylori) infection and metabolic syndrome (MetS) are highly prevalent worldwide. The emergence of relevant research suggesting a pathogenic linkage between H. pylori infection and MetS-related cardio-cerebrovascular diseases and neurodegenerative disorders, particularly through mechanisms involving brain pericyte deficiency, hyperhomocysteinemia, hyperfibrinogenemia, elevated lipoprotein-a, galectin-3 overexpression, atrial fibrillation, and gut dysbiosis, has raised stimulating questions regarding their pathophysiology and its translational implications for clinicians. An additional stimulating aspect refers to H. pylori and MetS-related activation of innate immune cells, mast cells (MC), which is an important, often early, event in systemic inflammatory pathologies and related brain disorders. Synoptically, MC degranulation may play a role in the pathogenesis of H. pylori and MetS-related obesity, adipokine effects, dyslipidemia, diabetes mellitus, insulin resistance, arterial hypertension, vascular dysfunction and arterial stiffness, an early indicator of atherosclerosis associated with cardio-cerebrovascular and neurodegenerative disorders. Meningeal MC can be activated by triggers including stress and toxins resulting in vascular changes and neurodegeneration. Likewise, H.pylori and MetS-related MC activation is linked with: (a) vasculitis and thromboembolic events that increase the risk of cardio-cerebrovascular and neurodegenerative disorders, and (b) gut dysbiosis-associated neurodegeneration, whereas modulation of gut microbiota and MC activation may promote neuroprotection. This narrative review investigates the intricate relationship between H. pylori infection, MetS, MC activation, and their collective impact on pathophysiological processes linked to neurodegeneration. Through a comprehensive search of current literature, we elucidate the mechanisms through which H. pylori and MetS contribute to MC activation, subsequently triggering cascades of inflammatory responses. This highlights the role of MC as key mediators in the pathogenesis of cardio-cerebrovascular and neurodegenerative disorders, emphasizing their involvement in neuroinflammation, vascular dysfunction and, ultimately, neuronal damage. Although further research is warranted, we provide a novel perspective on the pathophysiology and management of brain disorders by exploring potential therapeutic strategies targeting H. pylori eradication, MetS management, and modulation of MC to mitigate neurodegeneration risk while promoting neuroprotection.

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.

Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis.

Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barrett's esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.

A potential impact of Helicobacter pylori-related galectin-3 in neurodegeneration.

Neurodegeneration represents a component of the central nervous system (CNS) diseases pathogenesis, either as a disability primary source in the frame of prototype neurodegenerative disorders, or as a secondary effect, following inflammation, hypoxia or neurotoxicity. Galectins are members of the lectin superfamily, a group of endogenous glycan-binding proteins, able to interact with glycosylated receptors expressed by several immune cell types. Glycan-lectin interactions play critical roles in the living systems by involving and mediating a variety of biologically important normal and pathological processes, including cell-cell signaling shaping cell communication, proliferation and migration, immune responses and fertilization, host-pathogen interactions and diseases such as neurodegenerative disorders and tumors. This review focuses in the role of Galectin-3 in shaping responses of the immune system against microbial agents, and concretely, Helicobacter pylori (Hp), thereby potentiating effect of the microbe in areas distant from the ordinary site of colonization, like the CNS. We hereby postulate that gastrointestinal Hp alterations in terms of immune cell functional phenotype, cytokine and chemokine secretion, may trigger systemic responses, thereby conferring implications for remote processes susceptible in immunity disequilibrium, namely, the CNS inflammation and/or neurodegeneration.