The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Guzel, Tomasz; Mirowska‐Guzel, Dagmara

doi:10.3390/molecules27051680

Cited by 65 publications

(56 citation statements)

References 102 publications

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“…Serotonin synthesis also takes place in several cells such as immune cells (e.g., T-cells, B-cells, monocytes and macrophages) and pancreatic β-cells [61]. The effect of peripheral serotonin is dependent on the different receptors it is able to bind to [68]. The remaining production of serotonin occurs in the raphe nuclei located in the brainstem.…”

Section: Serotonin and Melatonin Pathwaymentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and therefore is its burden of disease as NALFD is a risk factor for cirrhosis and is associated with other metabolic conditions such as type II diabetes, obesity, dyslipidaemia and atherosclerosis. Linking these cardiometabolic diseases is a state of low-grade inflammation, with higher cytokines and c-reactive protein levels found in individuals with NAFLD, obesity and type II diabetes. A possible therapeutic target to decrease this state of low-grade inflammation is the metabolism of the essential amino-acid tryptophan. Its three main metabolic pathways (kynurenine pathway, indole pathway and serotonin/melatonin pathway) result in metabolites such as kynurenic acid, xanturenic acid, indole-3-propionic acid and serotonin/melatonin. The kynurenine pathway is regulated by indoleamine 2,3-dioxygenase (IDO), an enzyme that is upregulated by pro-inflammatory molecules such as INF, IL-6 and LPS. Higher activity of IDO is associated with increased inflammation and fibrosis in NAFLD, as well with increased glucose levels, obesity and atherosclerosis. On the other hand, increased concentrations of the indole pathway metabolites, regulated by the gut microbiome, seem to result in more favorable outcomes. This narrative review summarizes the interactions between tryptophan metabolism, the gut microbiome and the immune system as potential drivers of cardiometabolic diseases in NAFLD.

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Section: Serotonin and Melatonin Pathwaymentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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“…In addition to cell type, the receptor is another role-determining element. Activation of 5-HT7 receptors on antigen-presenting DCs and lipopolysaccharide-stimulated macrophages, likely with the cytokine production adjustment, diminishes inflammation severity ( 146 ). In contrast, by implicating the other receptor on the same cell (DC), serotonin leads to the elevation of IL-12 (through the NF-κB pathway), IL-17, IFN-γ, and ultimately the deterioration of inflammation ( 136 ).…”

Section: Behind the Scenementioning

confidence: 99%

Selective serotonin reuptake inhibitors and inflammatory bowel disease; Beneficial or malpractice

et al. 2022

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IBD, a chronic inflammatory disease, has been manifested as a growing health problem. No Crohn’s and Colitis councils have officially ratified anti-depressants as a routine regimen for IBD patients. However, some physicians empirically prescribe them to rectify functional bowel consequences such as pain and alleviate psychiatric comorbidities. On the other side, SSRIs’ prescription is accompanied by adverse effects such as sleep disturbances. Prolonged intermittent hypoxia throughout sleep disturbance such as sleep apnea provokes periodic reductions in the partial oxygen pressure gradient in the gut lumen. It promotes gut microbiota to dysbiosis, which induces intestinal inflammation. This phenomenon and evidence representing the higher amount of serotonin associated with Crohn’s disease challenged our previous knowledge. Can SSRIs worsen the IBD course? Evidence answered the question with the claim on anti-inflammatory properties (central and peripheral) of SSRIs and illuminated the other substantial elements (compared to serotonin elevation) responsible for IBD pathogenesis. However, later clinical evidence was not all in favor of the benefits of SSRIs. Hence, in this review, the molecular mechanisms and clinical evidence are scrutinized and integrated to clarify the interfering molecular mechanism justifying both supporting and disproving clinical evidence. Biphasic dose-dependent serotonin behavior accompanying SSRI shifting function when used up for the long-term can be assumed as the parameters leading to IBD patients’ adverse outcomes. Despite more research being needed to elucidate the effect of SSRI consumption in IBD patients, periodic prescriptions of SSRIs at monthly intervals can be recommended.

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“…Guzel et al and Mittal et al have mentioned seven types of serotonin receptors from 5-HT1-5-HT7 [ 6 , 7 ]. All receptors are G-protein coupled except 5-HT3 which is a ligand-gated ion channel receptor.…”

Section: Reviewmentioning

confidence: 99%

“…Their review also highlights the functions of each receptor. The functions have been summarized in Table 4 [ 7 ].…”

Section: Reviewmentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Review on the Efficacy and Safety of Selective Serotonin Reuptake Inhibitors in Gastrointestinal Motility Disorders: More Control, Less Risk

Acharekar¹,

Saldivia²,

Unnikrishnan³

et al. 2022

Cureus

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Gastrointestinal motility disorders have been thought to occur due to an imbalance in the interaction of the gut-brain axis, which is regulated by serotonin. This recent discovery can be exploited to find newer therapeutic agents such as selective serotonin reuptake inhibitors for functional gastrointestinal disorders.PubMed, PubMed Central (PMC), and Medline databases were used to obtain the data. Meta-analyses, systematic reviews, randomized control trials, and reviews were included and analyzed in the data.Of the 19240 studies, 23 were extracted, and after appropriate quality assessment, they were utilized in this systematic review. They included two meta-analyses, four systematic reviews, two randomized control trials, and 15 review articles. The systematic review focuses on the efficacy of selective serotonin reuptake inhibitors (SSRIs) as compared to other treatment modalities for disorders of gut-brain interaction. It explores various studies analyzing SSRIs for their mechanism of action, their desirable effects for treating irritable bowel syndrome, and their tolerability in patients.SSRIs are effective and safe in treating overall symptoms of gastrointestinal motility disorders, particularly constipation-predominant disorders. They seem to have a better side effect profile than other drugs. This should encourage physicians to prescribe SSRIs early on in the disease.

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The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Cited by 65 publications

References 102 publications

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Selective serotonin reuptake inhibitors and inflammatory bowel disease; Beneficial or malpractice

A Systematic Review on the Efficacy and Safety of Selective Serotonin Reuptake Inhibitors in Gastrointestinal Motility Disorders: More Control, Less Risk

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