Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets
Gary M. Mawe,Jill M. Hoffman +1 more
Reads0
Chats0
TLDR
Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies, and this work provides an overview of theseserotonergic actions and treatment strategies.Abstract:
Serotonin (5-HT) has been recognized for decades as an important signalling molecule in the gut, but it is still revealing its secrets. Novel gastrointestinal functions of 5-HT continue to be discovered, as well as distant actions of gut-derived 5-HT, and we are learning how 5-HT signalling is altered in gastrointestinal disorders. Conventional functions of 5-HT involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion and vasodilation. Activation of extrinsic vagal and spinal afferent fibres results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts nonconventional actions such as promoting inflammation and serving as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, originating in the gut, promotes haemostasis, influences bone development and serves many other functions. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhoea or constipation, respectively, and the synthetic enzyme tryptophan hydroxylase has also been targeted. Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. We provide an overview of these serotonergic actions and treatment strategies.read more
Citations
More filters
Journal ArticleDOI
Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis
Jessica M. Yano,Kristie B. Yu,Gregory P. Donaldson,Gauri G. Shastri,Phoebe Ann,Liang Ma,Cathryn R. Nagler,Rustem F. Ismagilov,Sarkis K. Mazmanian,Elaine Y. Hsiao +9 more
TL;DR: It is demonstrated that Indigenous spore-forming bacteria from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5- HT to the mucosa, lumen, and circulating platelets and elevating luminal concentrations of particular microbial metabolites increases colonic and blood5-HT in germ-free mice.
Journal ArticleDOI
The Microbiota-Gut-Brain Axis
John F. Cryan,Kenneth J. O’Riordan,Caitlin S. M. Cowan,Kiran V. Sandhu,Thomaz F.S. Bastiaanssen,Marcus Boehme,Martín Gabriel Codagnone,Sofia Cussotto,Christine Fülling,Anna V. Golubeva,Katherine E. Guzzetta,Minal Jaggar,Caitriona M. Long-Smith,Joshua M. Lyte,Jason A. Martin,Alicia Molinero-Perez,Gerard M. Moloney,Emanuela Morelli,Enrique Morillas,Rory C. O'Connor,Joana S Cruz-Pereira,Veronica L. Peterson,Kieran Rea,Nathaniel L. Ritz,Eoin Sherwin,Simon Spichak,Emily M. Teichman,Marcel van de Wouw,Ana Paula Ventura-Silva,Shauna E. Wallace-Fitzsimons,Niall P. Hyland,Gerard Clarke,Timothy G. Dinan +32 more
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Journal ArticleDOI
Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.
TL;DR: Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders.
Journal ArticleDOI
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease
TL;DR: This review gathers the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease and aims to facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
Journal ArticleDOI
Microbial tryptophan catabolites in health and disease
TL;DR: In this paper, the authors review emerging data suggesting that microbial tryptophan catabolites resulting from proteolysis are influencing host health and suggest that these metabolites activate the immune system through binding to the aryl hydrocarbon receptor (AHR), enhance the intestinal epithelial barrier, stimulate gastrointestinal motility, as well as secretion of gut hormones, exert anti-inflammatory, anti-oxidative or toxic effects in systemic circulation, and putatively modulate gut microbial composition.
References
More filters
Journal ArticleDOI
Functional Bowel Disorders
George F. Longstreth,W. Grant Thompson,William D. Chey,Lesley A. Houghton,Fermín Mearin,Robin C. Spiller +5 more
TL;DR: Employing a consensus approach, the working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations.
Journal ArticleDOI
Allelic Variation of Human Serotonin Transporter Gene Expression
Armin Heils,A. Teufel,Susanne Petri,Gerald Stöber,Peter Riederer,D. Bengel,Klaus-Peter Lesch +6 more
TL;DR: Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5‐HT) system and allele‐dependent differential 5‐HTT promoter activity may play a role in the expression and modulation of complex traits and behavior.
Journal ArticleDOI
Molecular, pharmacological and functional diversity of 5-HT receptors
TL;DR: The reward for unravelling this complex array of serotonin receptor--effector systems may be substantial, the ultimate prize being the development of important new drugs in a range of disease areas.
Journal ArticleDOI
The Expanded Biology of Serotonin
TL;DR: New work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins.
A Systematic Review and Meta-Analysis of Randomized Controlled Trials
TL;DR: The current evidence does not support the routine use of cryotherapy after total knee arthroplasty, and the patient-centered outcomes remain underinvestigated.
Related Papers (5)
The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders
Michael D. Gershon,Jan Tack +1 more