scholarly journals Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome

2020 ◽  
Vol 21 (22) ◽  
pp. 8664
Author(s):  
Yoshiyuki Mishima ◽  
Shunji Ishihara
Keyword(s):  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Molecular Mechanisms ◽  
Brain Activity ◽  
Functional Gastrointestinal Disorders ◽  
The Central Nervous System ◽  
Irritable Bowel ◽  
And Function ◽  
Preclinical And Clinical Studies ◽  
Neuroendocrine Factors

Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders, and accumulating evidence gained in both preclinical and clinical studies indicate the involvement of enteric microbiota in its pathogenesis. Gut resident microbiota appear to influence brain activity through the enteric nervous system, while their composition and function are affected by the central nervous system. Based on these results, the term “brain–gut–microbiome axis” has been proposed and enteric microbiota have become a potential therapeutic target in IBS cases. However, details regarding the microbe-related pathophysiology of IBS remain elusive. This review summarizes the existing knowledge of molecular mechanisms in the pathogenesis of IBS as well as recent progress related to microbiome-derived neurotransmitters, compounds, metabolites, neuroendocrine factors, and enzymes.

scholarly journals Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions

2016 ◽  
Vol 311 (5) ◽  
pp. G777-G784 ◽  
Author(s):  
Michael Camilleri ◽  
Ibironke Oduyebo ◽  
Houssam Halawi
Keyword(s):  
Fatty Acids ◽  
Irritable Bowel Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Short Chain Fatty Acids ◽  
Mucosal Barrier ◽  
Future Research ◽  
Enteroendocrine Cell ◽  
The Central Nervous System ◽  
Irritable Bowel

Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS.

scholarly journals Peripheral Mechanisms of Symptom Generation in Irritable Bowel Syndrome

2001 ◽  
Vol 15 (suppl b) ◽  
pp. 14B-16B ◽  
Author(s):  
Stephen M Collins
Keyword(s):  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Experimental Models ◽  
Low Grade ◽  
Sensory Physiology ◽  
Somatic Pain ◽  
Inflammatory Stimuli ◽  
The Central Nervous System ◽  
Irritable Bowel

There is considerable interest in the mechanisms that underlie symptom generation in irritable bowel syndrome (IBS) and particularly those mechanisms peripheral to higher centres in the nervous system. While the central nervous system is important in IBS, it is restricted largely to the role of behaviour in stress perception and symptom reporting. The gut and the autonomic nervous system are principal areas of research in identifying mechanisms underlying symptom generation and in the identification of new targets for drug development. While motility changes occur in IBS, they are neither specific nor predictable, and this is one reason why drugs aimed at influencing motility patterns have enjoyed limited success to date. This success has prompted interest in sensory physiology to explain pain and other discomforts expressed by patients with IBS. Patients with IBS exhibit intolerance to rectal distension and other manoeuvres of the gut, while exhibiting normal or raised thresholds for somatic pain. The mechanisms underlying the development of hyperalgesia or allodynia in the gut remain to be determined. In other systems and experimental models, low grade inflammation is a predicable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.

scholarly journals The Role of Mast Cells in Irritable Bowel Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kang Nyeong Lee ◽  
Oh Young Lee
Keyword(s):  
Irritable Bowel Syndrome ◽  
Mast Cells ◽  
Functional Gastrointestinal Disorders ◽  
Gastrointestinal Disorders ◽  
Future Directions ◽  
Intestinal Dysmotility ◽  
Immune Alterations ◽  
Irritable Bowel ◽  
And Function

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but its treatment is unsatisfactory as its pathophysiology is multifactorial. The putative factors of IBS pathophysiology are visceral hypersensitivity and intestinal dysmotility, also including psychological factors, dysregulated gut-brain axis, intestinal microbiota alterations, impaired intestinal permeability, and mucosal immune alterations. Recently, mucosal immune alterations have received much attention with the role of mast cells in IBS. Mast cells are abundant in the intestines and function as intestinal gatekeepers at the interface between the luminal environment in the intestine and the internal milieu under the intestinal epithelium. As a gatekeeper at the interface, mast cells communicate with the adjacent cells such as epithelial, neuronal, and other immune cells throughout the mediators released when they themselves are activated. Many studies have suggested that mast cells play a role in the pathophysiology of IBS. This review will focus on studies of the role of mast cell in IBS and the limitations of studies and will also consider future directions.

scholarly journals Potential neuro-immune therapeutic targets in irritable bowel syndrome

2020 ◽  
Vol 13 ◽  
pp. 175628482091063
Author(s):  
Maite Casado-Bedmar ◽  
Åsa V. Keita
Keyword(s):  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Enteric Nervous System ◽  
Immune Cells ◽  
Therapeutic Targets ◽  
Antidepressant Medication ◽  
Current Treatment ◽  
Dietary Interventions ◽  
The Central Nervous System ◽  
Irritable Bowel

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by recurring abdominal pain and disturbed bowel habits. The aetiology of IBS is unknown but there is evidence that genetic, environmental and immunological factors together contribute to the development of the disease. Current treatment of IBS includes lifestyle and dietary interventions, laxatives or antimotility drugs, probiotics, antispasmodics and antidepressant medication. The gut–brain axis comprises the central nervous system, the hypothalamic pituitary axis, the autonomic nervous system and the enteric nervous system. Within the intestinal mucosa there are close connections between immune cells and nerve fibres of the enteric nervous system, and signalling between, for example, mast cells and nerves has shown to be of great importance during GI disorders such as IBS. Communication between the gut and the brain is most importantly routed via the vagus nerve, where signals are transmitted by neuropeptides. It is evident that IBS is a disease of a gut–brain axis dysregulation, involving altered signalling between immune cells and neurotransmitters. In this review, we analyse the most novel and distinct neuro-immune interactions within the IBS mucosa in association with already existing and potential therapeutic targets.

scholarly journals The role of serotonin and diet in the prevalence of irritable bowel syndrome: a systematic review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Khushi Bruta ◽  
Vanshika ◽  
Kishnoor Bhasin ◽  
Bhawana
Keyword(s):  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Conventional Treatment ◽  
Treatment Options ◽  
The Body ◽  
Dietary Regulation ◽  
The Central Nervous System ◽  
Irritable Bowel ◽  
Indian Diet

AbstractSerotonin or 5-hydroxytryptamine (5-HT)- a neurotransmitter of both the Enteric Nervous System and the Central Nervous System is synthesized by the hydroxylation of L- tryptophan to 5-hydroxytryptophan.Serotonin has been associated with gut functions like assimilation and absorption, alongside the regulation of particle transport and fluid discharge in the gastrointestinal tract and its deficiency is found to be a prominent factor in the prevalence of gut disorders like Irritable Bowel Syndrome.For this review, we assessed the conventional treatment methods of common drugs, with the recently accredited treatment options like dietary regulation, exercise, meditation, and acupuncture. Having found that the most commonly used drugs exhibited various side effects like nausea, fatigue, rash, and dizziness, an in-depth evaluation of different Indian dietary patterns and their respective effects on tryptophan levels has been highlighted to formulate an ideal diet for patients with Irritable Bowel Syndrome (IBS). This review seeks to explore the numerous studies conducted to link IBS with the lack of serotonin production in the body, alongside exploring the evidence associating certain foods with raised tryptophan levels to hypothesize a suitable Indian diet.This review, in its essence, stresses the crucial need for further research on the dietary implications of common Indian foods and their FODMAP (Fermented Oligosaccharides, Disaccharides, Monosaccharides, And Polyols) contents, while underscoring the benefits of using unconventional and natural methods for the treatment of tryptophan-related gut disorders.

scholarly journals Importance of Non-pharmacological Approaches for Treating Irritable Bowel Syndrome: Mechanisms and Clinical Relevance

2021 ◽  
Vol 1 ◽  
Author(s):  
Albert Orock ◽  
Tian Yuan ◽  
Beverley Greenwood-Van Meerveld
Keyword(s):  
Irritable Bowel Syndrome ◽  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Visceral Pain ◽  
Behavioral Therapy ◽  
Functional Gastrointestinal Disorders ◽  
Experimental Models ◽  
Environmental Signals ◽  
Irritable Bowel ◽  
And Behavior

Chronic visceral pain represents a major unmet clinical need with the severity of pain ranging from mild to so severe as to prevent individuals from participating in day-to-day activities and detrimentally affecting their quality of life. Although chronic visceral pain can be multifactorial with many different biological and psychological systems contributing to the onset and severity of symptoms, one of the major triggers for visceral pain is the exposure to emotional and physical stress. Chronic visceral pain that is worsened by stress is a hallmark feature of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Current pharmacological interventions for patients with chronic visceral pain generally lack efficacy and many are fraught with unwanted side effects. Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain; however, the molecular mechanisms underlying CBT remain incompletely understood. Preclinical studies in experimental models of stress-induced visceral pain employing environmental enrichment (EE) as an animal model surrogate for CBT are unraveling the mechanism by which environmental signals can lead to long-lasting changes in gene expression and behavior. Evidence suggests that EE signaling interacts with stress and nociceptive signaling. This review will (1) critically evaluate the behavioral and molecular changes that lead to chronic pain in IBS, (2) summarize the pharmacological and non-pharmacological approaches used to treat IBS patients, and (3) provide experimental evidence supporting the potential mechanisms by which CBT ameliorates stress-induced visceral pain.

scholarly journals Alpha/Beta-Hydrolase Domain-Containing 6: Signaling and Function in the Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Haofuzi Zhang ◽  
Xin Li ◽  
Dan Liao ◽  
Peng Luo ◽  
Xiaofan Jiang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Serine Hydrolase ◽  
Pharmacological Interventions ◽  
The Central Nervous System ◽  
And Function ◽  
Arachidonoyl Glycerol ◽  
Brain Energy

Endocannabinoid (eCB) signaling plays an important role in the central nervous system (CNS). α/β-Hydrolase domain-containing 6 (ABHD6) is a transmembrane serine hydrolase that hydrolyzes monoacylglycerol (MAG) lipids such as endocannabinoid 2-arachidonoyl glycerol (2-AG). ABHD6 participates in neurotransmission, inflammation, brain energy metabolism, tumorigenesis and other biological processes and is a potential therapeutic target for various neurological diseases, such as traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, mental illness, and pain. This review summarizes the molecular mechanisms of action and biological functions of ABHD6, particularly its mechanism of action in the pathogenesis of neurological diseases, and provides a theoretical basis for new pharmacological interventions via targeting of ABHD6.

scholarly journals Role of Opioid Ligands in the Irritable Bowel Syndrome

1999 ◽  
Vol 13 (suppl a) ◽  
pp. 71A-75A ◽  
Author(s):  
Enrico Corazziari
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Opioid Receptor ◽  
Endogenous Opioids ◽  
Receptor Subtypes ◽  
Opioid Ligands ◽  
Opioid Receptor Subtypes ◽  
The Central Nervous System ◽  
Irritable Bowel

Endogenous opioid peptides – enkephalins, beta-endorphin and dynorphins – are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. Themureceptor agonists – morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide – have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials.

Sign in / Sign up

Export Citation Format

Share Document