• colitis
• developmental programming
• enteric nervous system
• fluoxetine
• gastrointestinal tract
• serotonin

• Pregnancy
• Humans
• Rats
• Animals
• Male
• Female
• Fluoxetine/toxicity
• Selective Serotonin Reuptake Inhibitors/toxicity
• Serotonin/metabolism
• Rats, Sprague-Dawley
• Rats, Wistar
• Prenatal Exposure Delayed Effects/metabolism
• Inflammation
• Colitis/chemically induced

• 350785 Crohn's and Colitis Foundation (CCF)

• Analgesics/chemistry
• Analgesics/pharmacology
• Drug Delivery Systems
• Drug Design
• Drug Discovery
• Humans
• Machine Learning
• Models, Biological
• Pain/drug therapy

• U24 CA224260 NCI NIH HHS
• U54 HL127624 NHLBI NIH HHS

• BCS class III-food effect
• GSK3352589
• IBS
• RET tyrosine kinase
• healthy volunteers
• pharmacokinetics

• Adult
• Female
• Humans
• Male
• Young Adult
• Area Under Curve
• Biological Availability
• Cohort Studies
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Food-Drug Interactions
• Half-Life
• Protein Kinase Inhibitors/administration & dosage
• Protein Kinase Inhibitors/adverse effects
• Protein Kinase Inhibitors/pharmacokinetics
• Proto-Oncogene Proteins c-ret/antagonists & inhibitors

Ample evidence indicates the efficacy of serotonin type 3 (5-HT₃) receptor antagonists in the treatment of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Mirtazapine is an atypical antidepressant with a well-known 5-HT₃ receptor antagonist property. This study, therefore, was undertaken to investigate whether compared to placebo, mirtazapine would be efficacious and safe in the treatment of patients with IBS-D.

From November 2019 until July 2020, 67 patients meeting Rome IV criteria for IBS-D were randomized in a double-blind fashion into either the mirtazapine treatment group (n = 34) or the placebo treatment group (n = 33). Patients started with mirtazapine 15 mg/day at bedtime for one-week; after which the dose was increased to 30 mg/day for an additional 7-week. Outcomes included changes in the total IBS symptom severity score (IBS-SSS), Hospital anxiety and depression scale score (HADS), and IBS Quality of Life. Additionally, changes in the diary-based symptoms scores including pain, urgency of defecation, bloating, stool frequency, and stool consistency based on the 7-point Bristol Stool Form Scale (BSFS), and a number of days per week with pain, urgency, diarrhea, or bloating, once during the 1-week run-in period, and once during the last week of treatment were recorded.

All analyses were performed on an Intention-to-Treat (ITT) analysis data set. The results showed compared to placebo, mirtazapine is more efficacious in decreasing the severity of IBS symptoms (P-value = 0.002). Further, at the end of the treatment period, all diary-derived symptoms except bloating showed significantly more improvement in the mirtazapine-treated subjects compared to the placebo-treated subjects. While was well-tolerated, mirtazapine also significantly improved the patients’ quality of life (P-value = 0.04) and anxiety symptoms (P-value = 0.005).

Overall, mirtazapine seems to have a potential benefit in the treatment of patients with IBS-D, particularly those with concomitant psychological symptoms. However, further studies are warranted to determine whether these findings are replicated.

Trial registration: Registration number at Iranian Registry of Clinical Trials: IRCT20120215009014N311. Registration date: 2019-10-21.

• 5-hydroxytryptamine
• Diarrhea
• Irritable bowel syndrome
• Mirtazapine

• 5-HT3 receptor modulators
• psychosis
• schizophrenia
• serotonin
• structure-activity relationship

• Gastrointestinal Diseases/drug therapy
• Humans
• Nausea
• Receptors, Serotonin, 5-HT3
• Serotonin
• Serotonin Antagonists/pharmacology

• A549 Cells
• Animals
• Cell Line, Tumor
• Colon/drug effects
• Colon/enzymology
• Disease Models, Animal
• Female
• Humans
• Irritable Bowel Syndrome/drug therapy
• Irritable Bowel Syndrome/enzymology
• Male
• Mice
• Mice, Transgenic
• Pregnancy
• Protein Kinase Inhibitors/pharmacology
• Protein Kinase Inhibitors/therapeutic use
• Proto-Oncogene Proteins c-ret/antagonists & inhibitors
• Proto-Oncogene Proteins c-ret/metabolism
• Rats
• Rats, Long-Evans
• Rats, Sprague-Dawley

• K08 DK110532 NIDDK NIH HHS
• R01 NS015547 NINDS NIH HHS

The efficacy and acceptance of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet in Asian adults with irritable bowel syndrome (IBS) remain uncertain. We aimed to describe our early experience in a single center with a dedicated gastroenterology dietetic service.

Consecutive patients with IBS referred to our dedicated Dietetic Gastroenterology Clinic between February 2016 and May 2016 were screened. A low FODMAP diet was instituted as per standard protocol. Data on demographic and clinical variables were obtained from patients’ records and prospective telephone interviews.

A total of 16 patients, with a median age of 67 ± 13.57 years; female gender n = 10 (62.5%); ethnicity: Chinese n = 8 (50%), Indian n = 5 (31.25%), and Malay n = 3 (18.75%) with IBS, were included in the study. Compliance with the low FODMAP diet was complete in 8 of 16 (50%) patients, partial in 4 of 16 (25%), and 4 of 16 (25%) could not comply with the diet at all. Improvement in symptoms were reported in 11 of 16 (68.8%) patients. Among patients who complied (complete/partial) with the low FODMAP diet, predominant symptom improvement was reported as follows: abdominal pain 3 of 5 (60%), abdominal bloating/distension 7 of 10 (70%), and flatulence 7 of 8 (87.5%). Patients with the IBS‐D subtype appeared to have the greatest improvement in stool consistency (87.5% IBS‐D vs 12.5% non‐IBS‐D, P = 0.009).

Based on our pilot observational study of a relatively small sample of Asian IBS patients, compliance with a low FODMAP diet appears to be low. Further larger studies are required to verify our observation.

• Asia
• early experience
• irritable bowel syndrome
• low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet
• treatment

• Diarrhea
• Down-Regulation
• Gene Expression Regulation
• Genetic Association Studies
• Humans
• Irritable Bowel Syndrome/genetics
• Irritable Bowel Syndrome/metabolism
• Jejunum/metabolism
• Jejunum/pathology
• MicroRNAs/genetics
• Mutation/genetics
• Phenotype
• Polymorphism, Single Nucleotide
• Protein Binding/genetics
• Quality of Life
• Receptors, Serotonin, 5-HT4/genetics
• Receptors, Serotonin, 5-HT4/metabolism
• Signal Transduction
• Work Performance

• R01 DK048351 NIDDK NIH HHS

• Fibromyalgia
• drugs
• exploration technology
• therapeutic patents

This review summarizes the published clinical studies concerning the management of irritable bowel syndrome (IBS) using restriction of Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyols in the diet (low FODMAP diet). In recent years, the data supporting low FODMAP diet for the management of IBS symptoms have emerged, including several randomized controlled trials, case-control studies, and other observational studies. Unlike most dietary manipulations tried in the past to alleviate gastrointestinal symptoms of IBS, all studies on low FODMAP diet have consistently shown symptomatic benefits in the majority of patients with IBS. However, dietary adherence by the patients and clear dietary intervention led by specialized dietitians appear to be vital for the success of the diet. Up to 86% of patients with IBS find improvement in overall gastrointestinal symptoms as well as individual symptoms such as abdominal pain, bloating, constipation, diarrhea, abdominal distention, and flatulence following the diet. FODMAP restriction reduces the osmotic load and gas production in the distal small bowel and the proximal colon, providing symptomatic relief in patients with IBS. Long-term health effects of a low FODMAP diet are not known; however, stringent FODMAP restriction is not recommended owing to risks of inadequate nutrient intake and potential adverse effects from altered gut microbiota. In conclusion, the evidence to date strongly supports the efficacy of a low FODMAP diet in the treatment of IBS. Further studies are required to understand any potential adverse effects of long-term restriction of FODMAPs.

• gastrointestinal symptoms
• irritable bowel syndrome
• low FODMAP diet

• Carbohydrates
• Colon
• Food
• Gastrointestinal Symptoms

• drug discovery
• dysfunctional pain
• fibromyalgia
• interstitial cystitis
• irritable bowel syndrome
• unknown pathophysiology

AIM: To investigate the effects of a low fermentable, oligosaccharides, disaccharides, monosaccharides and polyols diet (LFD) and the probiotic Lactobacillus rhamnosus GG (LGG) in irritable bowel syndrome (IBS).

METHODS: Randomised, unblinded controlled trial on the effect of 6-wk treatment with LFD, LGG or a normal Danish/Western diet (ND) in patients with IBS fulfilling Rome III diagnostic criteria, recruited between November 2009 and April 2013. Patients were required to complete on a weekly basis the IBS severity score system (IBS-SSS) and IBS quality of life (IBS-QOL) questionnaires in a specially developed IBS web self-monitoring application. We investigated whether LFD or LGG could reduce IBS-SSS and improve QOL in IBS patients.

RESULTS: One hundred twenty-three patients (median age 37 years, range: 18-74 years), 90 (73%) females were randomised: 42 to LFD, 41 to LGG and 40 to ND. A significant reduction in mean ± SD of IBS-SSS from baseline to week 6 between LFD vs LGG vs ND was revealed: 133 ± 122 vs 68 ± 107, 133 ± 122 vs 34 ± 95, P < 0.01. Adjusted changes of IBS-SSS for baseline covariates showed statistically significant reduction of IBS-SSS in LFD group compared to ND (IBS-SSS score 75; 95%CI: 24-126, P < 0.01), but not in LGG compared to ND (IBS-SSS score 32; 95%CI: 18-80, P = 0.20). IBS-QOL was not altered significantly in any of the three groups: mean ± SD in LFD 8 ± 18 vs LGG 7 ± 17, LFD 8 ± 18 vs ND 0.1 ± 15, P = 0.13.

CONCLUSION: Both LFD and LGG are efficatious in patients with IBS.

• Irritable bowel syndrome
• Web-based management
• Low FODMAP diet
• Lactobacillus rhamnosus GG
• Disease severity
• Irritable bowel syndrome-quality of life

• Adolescent
• Adult
• Aged
• Denmark
• Diet, Carbohydrate-Restricted
• Dietary Carbohydrates/metabolism
• Feasibility Studies
• Female
• Fermentation
• Humans
• Internet
• Irritable Bowel Syndrome/diagnosis
• Irritable Bowel Syndrome/diet therapy
• Irritable Bowel Syndrome/metabolism
• Irritable Bowel Syndrome/microbiology
• Lacticaseibacillus rhamnosus/physiology
• Male
• Middle Aged
• Patient Dropouts
• Probiotics/therapeutic use
• Quality of Life
• Severity of Illness Index
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome
• Young Adult

Psychological stress is an important factor for the development of irritable bowel syndrome (IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stress-sensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.

• Psychological stress
• Irritable bowel syndrome
• Microbiota-gut-brain axis
• Immune activation

• Animals
• Brain/physiopathology
• Humans
• Intestines/innervation
• Irritable Bowel Syndrome/etiology
• Irritable Bowel Syndrome/physiopathology
• Irritable Bowel Syndrome/psychology
• Irritable Bowel Syndrome/therapy
• Prognosis
• Risk Factors
• Stress, Psychological/complications
• Stress, Psychological/physiopathology
• Stress, Psychological/psychology
• Stress, Psychological/therapy

• Abdominal Pain/etiology
• Abdominal Pain/therapy
• Animals
• Antidepressive Agents/therapeutic use
• Cognitive Behavioral Therapy/methods
• Diarrhea/etiology
• Humans
• Hypnosis/methods
• Irritable Bowel Syndrome/complications
• Irritable Bowel Syndrome/physiopathology
• Irritable Bowel Syndrome/therapy
• Parasympatholytics/therapeutic use
• Probiotics/therapeutic use

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with a high incidence in the general population. The diagnosis of IBS is mainly based on exclusion of other intestinal conditions through the absence of inflammatory markers and specific antigens. The current pharmacological treatment approaches available focus on reducing symptom severity while often limiting quality of life because of significant side effects. This has led to an effectiveness gap for IBS patients that seek further relief to increase their quality of life. Complementary and alternative medicines (CAM) have been associated with a higher degree of symptom management and quality of life in IBS patients. Over the past decade, a number of important clinical trials have shown that specific herbal therapies (peppermint oil and Iberogast^®), hypnotherapy, cognitive behavior therapy, acupuncture, and yoga present with improved treatment outcomes in IBS patients. We propose an integrative approach to treating the diverse symptoms of IBS by combining the benefits of and need for pharmacotherapy with known CAM therapies to provide IBS patients with the best treatment outcome achievable. Initial steps in this direction are already being considered with an increasing number of practitioners recommending CAM therapies to their patients if pharmacotherapy alone does not alleviate symptoms sufficiently.

• Irritable bowel syndrome
• Complementary and alternative medicine
• Hypnotherapy
• Cognitive behavioral therapy
• Herbal therapy
• Peppermint

• Acupuncture Therapy
• Cognitive Behavioral Therapy
• Complementary Therapies/methods
• Humans
• Hypnosis
• Irritable Bowel Syndrome/diagnosis
• Irritable Bowel Syndrome/therapy
• Phytotherapy
• Plant Preparations/therapeutic use
• Treatment Outcome
• Yoga

Irritable bowel syndrome (IBS) is a common disorder, reported to be found in 5%-20% of the general population. Its management accounts for up to 25% of a gastroenterologist’s workload in the outpatient department, and the main symptoms are abdominal pain, bloating, and altered bowel habits. Despite a great amount of available pharmacological treatments aimed at a wide variety of gastrointestinal and brain targets, many patients have not shown adequate symptom relief. In recent years, there has been increasing evidence to suggest that psychological treatments, in particular cognitive-behavioral therapy (CBT), are effective for the management of IBS. This review discusses CBT for the management of IBS. CBT has proved to be effective in alleviating the physical and psychological symptoms of IBS and has thus been recommended as a treatment option for the syndrome.

• Cognitive-behavioral therapy
• Irritable bowel syndrome
• Psychological treatment

• Cognitive Behavioral Therapy
• Humans
• Irritable Bowel Syndrome/diagnosis
• Irritable Bowel Syndrome/physiopathology
• Irritable Bowel Syndrome/psychology
• Irritable Bowel Syndrome/therapy
• Treatment Outcome

AIM: To determine the influence of Fagopyrum cymosum tablets on immune inflammation and visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome (IBS).

METHODS: IBS was induced in neonatal rats by feeding a high lactose diet, chronic bandaged-stress and inserting the tail. Rats were randomly divided into six groups: a normal control group (group A), a model group (group B), high-, medium- and low-dose Fagopyrum cymosum groups (group C, D and E), and a Gushen Chang'an group (group F). Groups C, D and E received oral administration of 6, 3 and 1.5 g/(kg•d) of Fagopyrum cymosum tablets, respectively, once every day for four weeks; group F received oral administration of 2 g/(kg•d) of Gushen Chang'an; Groups A and B received oral administration of equal volume of normal saline. The colon motion, abdominal withdrawal reflex (AWR) of colorectal distention and abdominal electrical activity were observed. Radioimmunoassay was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17), IL-10, substance P (SP) and calcitonin gene-related peptide (CGRP). Fluorescent quantitative PCR was used to detect the expression of 5-hydroxytryptamine (5-HT), 5-hydroxytryptamine 3 receptor (5-HT3R), neurokinin receptor 1 (NK1R) and intracellular adhesion molecule-1 (ICAM-1) mRNAs in the intestinal tissue.

RESULTS: Fagopyrum cymosum could decrease colon motion and visceral hypersensitivity in IBS rats (P < 0.05 or 0.01). In the Fagopyrum cymosum treatment groups, serum levels of TNF-α (2.81 ng/L ± 0.67 ng/L, 2.76 ng/L ± 0.31 ng/L, 2.91 ng/L ± 0.77 ng/L vs 3.77 ng/L ± 0.44 ng/L), IL-17 (2.01 ng/L ± 0.76 ng/L, 2.14 ng/L ± 0.29 ng/L, 1.98 ng/L ± 0.11 ng/L vs 2.47 ng/L ± 0.33 ng/L) and SP (38.22 pg/mL ± 3.15 pg/mL, 37.55 pg/mL ± 2.63 pg/mL, 42.01 pg/mL ± 3.79 pg/mL vs 43.19 pg/mL ± 4.28 pg/mL) were significantly lower, and those of IL-10 (137.25 ng/L ± 6.2 ng/L, 135.90 ng/L ± 4.4 ng/L, 121.70 ng/L ± 5.11 ng/L vs 82.09 ng/L ± 5.33 ng/L) and CGRP (155.09 ng/L ± 4.38 ng/L, 142.02 ng/L ± 2.44 ng/L, 158.25 ng/L ± 4.02 ng/L vs 107.31 ng/L ± 3.96 ng/L) were significantly higher than those in the model group (all P < 0.05 or 0.01). The mRNA expression of 5-HT (0.74 ± 0.43, 0.97 ± 0.91, 0.66 ± 0.29 vs 1.27 ± 0.45), 5-HT3R (1.01 ± 0.35, 1.14 ± 0.76, 1.47 ± 0.65 vs 1.61 ± 0.03), NK1R (1.07 ± 0.58, 0.98 ± 0.67, 0.88 ± 0.79 vs 1.47 ± 0.94) and ICAM-1 (0.81 ± 0.55, 0.96 ± 0.19, 0.72 ± 0.93 vs 1.33 ± 0.26) in the intestinal tissue was down-regulated after treatment with Fagopyrum cymosum tablets (P < 0.05 or 0.01), especially in the high-dose group.

CONCLUSION: Fagopyrum cymosum tablets can reduce visceral hypersensitivity and inhibit inflammatory immune response in IBS-D rats in a concentration-dependent manner.

• Fagopyrum cymosum tablets
• Irritable bowel syndrome
• Immune inflammation
• Visceral hypersensitivity