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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., Competing Interests: Declaration of competing interest Jannis Kountouras: Declarations of interest: none. Marina Boziki: Declarations of interest: none. Evangelos Kazakos: Declarations of interest: none. Paschalis Theotokis: Declarations of interest: none. Evangelia Kesidou: Declarations of interest: none. Maria Nella: Declarations of interest: none. Christos Bakirtzis: Declarations of interest: none. Eleni Karafoulidou: Declarations of interest: none. Elisabeth Vardaka: Declarations of interest: none. Maria C. Mouratidou: Declarations of interest: none. Foteini Kyrailidi: Declarations of interest: none. Maria Tzitiridou-Chatzopoulou: Declarations of interest: none. Eirini Orovou: Declarations of interest: none. Evaggelia Giartza-Taxidou: Declarations of interest: none. Georgia Deretzi: Declarations of interest: none. Nikolaos Grigoriadis: Declarations of interest: none. Michael Doulberis: Declarations of interest: none., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD), also recently referred as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by hepatocyte steatosis in the setting of metabolic risk conditions and in the absence of an underlying precursor, for instance alcohol consumption, hepatotropic viruses and hepatotoxic drugs. A possible association between NAFLD and depression has been proposed, owing to intersecting pathophysiological pathways. This narrative review aimed to summarize the current evidence that illustrate the potential pathophysiological and clinical linkage between NAFLD-related metabolic state and depression. Prefrontal cortex lesions are suggested to be a consequence of liver steatosis-associated systematic hyperinflammatory state, a phenomenon also occurring in depression. In addition, depressive symptoms are present in neurotransmitter imbalances. These abnormalities seem to be correlated with NAFLD/MAFLD, in terms of insulin resistance (IR), ammonia and gut dysbiosis' impact on serotonin, dopamine, noradrenaline levels and gamma aminobutyric acid receptors. Furthermore, reduced levels of nesfatin-1 and copine-6-associated BDNF (brain-derived neurotrophic factor) levels have been considered as a probable link between NAFLD and depression. Regarding NAFLD-related gut dysbiosis, it stimulates mediators including lipopolysaccharides, short-chain fatty acids and bile acids, which play significant role in depression. Finally, western diet and IR, which are mainstay components of NAFLD/MAFLD, are, also, substantiated to affect neurotransmitters in hippocampus and produce neurotoxic lipids that contribute to neurologic dysfunction, and thus trigger emotional disturbances, mainly depressive symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)