Chitin-glucan improves important pathophysiological features of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most frequent and debilitating conditions leading to gastroenterological referrals. However, recommended treatments remain limited, yielding only limited therapeutic gains. Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority. To provide an alternative approach to managing patients with IBS, we performed preclinical molecular, cellular, and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS. AIM: To evaluate the roles of CG in visceral analgesia, intestinal inflammation, barrier function, and to develop computational molecular models. METHODS: Visceral pain was recorded through colorectal distension (CRD) in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS [15 milligrams (mg)/kilogram (kg)] in 33 Sprague-Dawley rats. Intracolonic pressure was regularly assessed during the 9 wk-experiment (weeks 0, 3, 5, and 7) in animals receiving CG (n = 14) at a human equivalent dose (HED) of 1.5 g/d or 3.0 g/d and compared to negative control (tap water, n = 11) and positive control (phloroglucinol at 1.5 g/d HED, n = 8) groups. The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate (DSS) administered in their drinking water during 14 d. HT-29 cells under basal conditions and after stimulation with lipopolysaccharide (LPS) were treated with CG to evaluate changes in pathways related to analgesia (µ-opioid receptor (MOR), cannabinoid receptor 2 (CB2), peroxisome proliferator-activated receptor alpha, inflammation [interleukin (IL)-10, IL-1b, and IL-8] and barrier function [mucin 2-5AC, claudin-2, zonula occludens (ZO)-1, ZO-2] using the real-time PCR method. Molecular modelling of CG, LPS, lipoteichoic acid (LTA), and phospholipomannan (PLM) was developed, and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations. Data were expressed as the mean ± SEM. RESULTS: Daily CG orally-administered to rats or mice was well tolerated without including diarrhea, visceral hypersensitivity, or inflammation, as evaluated at histological and molecular levels. In a model of CRD, CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14% after 2 wk of administration (P < 0.01) and reduced inflammation intensity by 50%, resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis. To better reproduce the characteristics of visceral pain in patients with IBS, we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity. CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20% five weeks after colitis induction (P < 0.01). When the CG dosage was increased to 3.0 g/d HED, this analgesic effect surpassed that of the spasmolytic agent phloroglucinol, manifesting more rapidly within 3 wk and leading to a 50% inhibition of pain perception (P < 0.0001). The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved, at least in part, a significant induction of MOR, CB2 receptor, and IL-10, as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8. CG also significantly upregulated barrier-related genes including muc5AC, claudin-2, and ZO-2. Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids, sequestering gram-negative LPS and gram-positive LTA bacterial toxins, as well as PLM in fungi at the lowesr energy conformations. CONCLUSION: CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.

Functional Constipation and Obstructed Defecation.

Constipation encompasses symptoms of decreased colonic motility or difficulty with the defecation process. As a broad definition, this can be inclusive of functional constipation (FC) or colonic inertia, obstructed defecation (OD), and irritable bowel syndrome-constipation type (IBS-CS). After excluding IBS-C, FC and OD diagnosis and management require a multidisciplinary approach often involving nutritionists, pelvic floor therapists, urogynecologists, and colon and rectal surgeons. Differentiating the presence or absence of each can direct therapy and prognosticate chances for improvement in this often complex combination of disorders.

Psychometric Evaluation of the Diary for Irritable Bowel Syndrome Symptoms-Constipation in a Prospective Observational Study.

OBJECTIVES: To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. METHODS: Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. RESULTS: The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. CONCLUSIONS: The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials.

Comparison of pancreatic enzyme abnormalities and protease-activated receptor-2-positive eosinophils in the duodenum of patients with functional dyspepsia-irritable bowel syndrome overlap with functional dyspepsia alone in Asian populations.

BACKGROUND AND AIM: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group. METHODS: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining. RESULTS: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone. CONCLUSIONS: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations.

Gut enterochromaffin cells drive visceral pain and anxiety.

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3-5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.

Antibiotics, gut microbiota, and irritable bowel syndrome: What are the relations?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.

EphrinB2/ephB2 activation facilitates colonic synaptic potentiation and plasticity contributing to long-term visceral hypersensitivity in irritable bowel syndrome.

AIMS: Sustained visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS) could be partially explained by enteric neural remodeling. Particularly, synaptic plasticity in the enteric nervous system, a form of enteric "memory", has been speculated as a participant in the pain maintenance in IBS. This study aimed to elucidate the role of ephrinB2/ephB2 in enteric synaptic plasticity and visceral pain in IBS. MATERIALS AND METHODS: EphrinB2/ephB2 expression and synaptic plasticity were assessed in colonic tissues from IBS patients, and rats induced by Trichinella spiralis infection and those treated with ephB2-Fc (an ephB2 receptor blocker) or ifenprodil (a selective NR2B antagonist). Furthermore, abdominal withdrawal reflex scores to colorectal distention and mesenteric afferent firing were assessed. EphrinB2-Fc(an ephB2 receptor activator) induced enteric synaptic plasticity was further evaluated in longitudinal muscle-myenteric plexus(LMMP) cultures and primary cultured myenteric neurons. KEY FINDINGS: EphrinB2/ephB2 was specifically expressed in colonic nerves and upregulated in IBS patients and rats, which was correlated with pain severity. The functional synaptic plasticity, visceral sensitivity to colorectal distention and colonic mesenteric afferent activity to mechanical and chemical stimulus were enhanced in IBS rats, and were blocked by ephB2-Fc or ifenprodil treatment. EphrinB2-Fc promoted the phosphorylation of NR2B in IBS rats and LMMP cultures, and could mediate sustained neural activation via increased [Ca2+]i and raised expression of synaptic plasticity-related early immediate genes, including c-fos and arc. SIGNIFICANCE: EphrinB2/ephB2 facilitated NR2B-mediated synaptic potentiation in the enteric nervous system that may be a novel explanation and potential therapeutic target for sustained pain hypersensitivity in IBS.

Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.

Irritable bowel syndrome in inflammatory bowel disease. Synergy in alterations of the gut-brain axis? / Síndrome de intestino irritable en la enfermedad inflamatoria intestinal. ¿Sinergia en las alteraciones del eje cerebro-intestino?

The presence of digestive symptoms associated with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in remission is a topic of growing interest. Although there is heterogeneity in clinical studies regarding the use of IBD remission criteria and the diagnosis of IBS, the available data indicate that the IBD-IBS overlap would affect up to one third of patients in remission, and they agree on the finding of a negative impact on the mental health and quality of life of the individuals who suffer from it. The pathophysiological bases that would explain this potential overlap are not completely elucidated; however, an alteration in the gut-brain axis associated with an increase in intestinal permeability, neuroimmune activation and dysbiosis would be common to both conditions. The hypothesis of a new clinical entity or syndrome of "Irritable Inflammatory Bowel Disease" or "Post-inflammatory IBS" is the subject of intense investigation. The clinical approach is based on certifying the remission of IBD activity and ruling out other non-inflammatory causes of potentially treatable persistent functional digestive symptoms. In the case of symptoms associated with IBS and in the absence of sufficient evidence, comprehensive and personalized management of the clinical picture (dietary, pharmacological and psychotherapeutic measures) should be carried out, similar to a genuine IBS.

Non-pharmacologic strategies for the management of intestinal inflammation.

Inflammatory bowel diseases, irritable bowel syndrome, and mucositis are characterized by intestinal inflammation, but vary according to their pathological mechanisms, severity, location, and etiology. Significant intestinal inflammation that occurs in these diseases induces weight loss, nutritional depletion, and gastrointestinal tract dysfunction. Nutritional support is important in alleviating symptoms and improving patients' quality of life. In this review, we summarize some nutritional components used to manage intestinal disorders. These include fatty acids, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and low FODMAP (LFD) diets. These components and LFD diets have been studied and clinical trials have been designed to develop new strategies to alleviate intestinal inflammation and improve the quality of life. Clinical trials on their use in intestinal inflammation do not allow firm conclusions to be drawn mainly because of the heterogeneity of the dose used and the study design or their inconclusive results. However, in the majority of cases, the use of omega-3, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and LFD improve the health.

Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice.

Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.

The role of serum gastric peptide ghrelin hormone level in irritable bowel syndrome at Zagazig University Hospitals.

Generalized dysmotility of the gastrointestinal tract develops in individuals with irritable bowel syndrome (IBS). The ghrelin hormone appears to be critical in controlling gastrointestinal motility. We aimed to evaluate serum ghrelin levels in people with IBS and to demonstrate its role in IBS pathophysiology. This study included 32 individuals with IBS (16 with constipation and 16 with diarrhea) and 16 healthy individuals as controls. Blood specimens were collected from patients and controls following an overnight fast. Total ghrelin level was detected in plasma by commercially available ELISA Kit. There were significant differences in the serum levels of ghrelin between the control group and both types of IBS. The mean±SD of ghrelin level in the control group was 2.608±0.714 pg/ml, and that of both types of IBS was 5.782±2.450 pg/ml (P-value<0.001). There was a significant variation between the control and IBS-D groups (mean±SD: 7.838±1.687 pg/ml, p-value<0.001). Also, we indicated a considerable difference between the control and IBS-C groups (mean±SD: 3.726±0.740 pg/ml, P-value<0.001). In comparing the IBS-D group and IBS-C group, we found a highly considerable variation between the two groups (p-value<0.001). This means that serum ghrelin levels were significantly greater in IBS-D than in IBS-C and the control group. Our findings concluded that serum ghrelin level was higher among the IBS-D group than in the IBS-C and control groups. The ghrelin hormone may play a vital role in IBS pathophysiology.

Artículo de revisión: abordaje del síndrome de intestino irritable en APS / Review article: Irritable bowel syndrome approach in PHC

El síndrome de intestino irritable es un trastorno digestivo funcional recientemente reconocido como una alteración en el nivel intestino-cerebral que no se explica por alteraciones morfológicas, metabólicas o neurológicas demostrables por las técnicas diagnósticas habituales, caracterizándose por la presencia de dolor y distensión abdominal recurrente asociado a alteraciones del ritmo deposicional, ya sea en forma de constipación, diarrea o ambas. La prevalencia oscila entre los 6-11% dependiendo de los criterios diagnósticos utilizados y la zona geográfica, en Chile no hay datos actuales. Su fisiopatología es multifactorial, donde ninguno explica por si solo el síndrome. El diagnóstico es positivo basado en los criterios de Roma IV establecidos en el año 2016, a su vez es imperante establecer un subtipo de SII para realizar el manejo adecuado, es así como podemos tener un SII con predominio de constipación, diarrea, mixto o indeterminado. El manejo consta de la educación al paciente, una buena relación médico-paciente, dieta adecuada, actividad física aeróbica y otros tratamientos no farmacológicos, sumado a antiespasmódicos, antidiarreicos y fibra soluble, dependiendo del síntoma predominante.

Irritable bowel syndrome (IBS) is a functional digestive disorder recently recognized as an alteration in the gut-brain axis which can´t be explained by morphological, metabolic or neurological alterations demonstrable by the usual diagnostic techniques, characterized by the presence of recurrent abdominal pain and distention associated with alterations in the stool rhythm, either in the form of constipation, diarrhea or both. The prevalence ranges between 6-11% according to the diagnostic criteria used and the geographical area, in Chile there's no current data. Its pathophysiology is multifactorial, where any of them explains the syndrome itself. The diagnosis is positive based on the Rome IV criteria established in 2016, it is imperative to establish a subtype of IBS to carry out the appropriate management, This is how we can have IBS with a predominance of constipation, diarrhea, mixed or indeterminate Management consists of patient education, a good doctor-patient relationship, adequate diet, aerobic physical activity and other non-pharmacological treatments, added to antispasmodics, antidiarrheals and soluble fiber, depending on the predominant symptom.

Aberrant Gut-To-Brain Signaling in Irritable Bowel Syndrome - The Role of Bile Acids.

Functional bowel disorders such as irritable bowel syndrome (IBS) are common, multifactorial and have a major impact on the quality of life of individuals diagnosed with the condition. Heterogeneity in symptom manifestation, which includes changes in bowel habit and visceral pain sensitivity, are an indication of the complexity of the underlying pathophysiology. It is accepted that dysfunctional gut-brain communication, which incorporates efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones and local paracrine and neurocrine factors, such as host and microbially-derived signaling molecules, underpins symptom manifestation. This review will focus on the potential role of hepatic bile acids in modulating gut-to-brain signaling in IBS patients. Bile acids are amphipathic molecules synthesized in the liver, which facilitate digestion and absorption of dietary lipids. They are also important bioactive signaling molecules however, binding to bile acid receptors which are expressed on many different cell types. Bile acids have potent anti-microbial actions and thereby shape intestinal bacterial profiles. In turn, bacteria with bile salt hydrolase activity initiate the critical first step in transforming primary bile acids into secondary bile acids. Individuals with IBS are reported to have altered microbial profiles and modified bile acid pools. We have assessed the evidence to support a role for bile acids in the pathophysiology underlying the manifestation of IBS symptoms.

Obesity Exacerbates Irritable Bowel Syndrome-Related Sleep and Psychiatric Disorders in Women With Polycystic Ovary Syndrome.

Background/Objectives: Polycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS) share similar clinical and psychosocial features. We aimed to investigate the clinical characteristics of IBS in women with PCOS, and its relationship with obesity, metabolic and hormonal profiles, as well as sleep and psychiatric disorders. Subjects/Methods: This is a cross-sectional case-control study of 431 untreated women with PCOS and 259 healthy volunteers. All participants were assessed with a comprehensive clinical evaluation and two questionnaires: the Athens Insomnia Scale (AIS) and the Brief Symptom Rating Scale (BSRS-5). IBS was diagnosed using the Rome III criteria. Obesity was defined as a BMI ≥30 kg/m2. Anthropometric measurements, metabolic, hormonal profiles, and psychosocial morbidities were compared. Results: Women with PCOS were more likely to have IBS (10.7% vs 5.8%, p=0.029) and obesity (29% vs 4%, p<0.001) than healthy volunteers. Mixed-type IBS (IBS-M) was the most common subtype (74%) among patients with PCOS and IBS. There was a higher prevalence of psychiatric morbidities (total BSRS-5 score ≥10) in women with PCOS than in healthy women (11.4% vs 3.5%, p<0.001). Women with PCOS and IBS were more likely to have sleep difficulties (67.4% vs 30.9%, p<0.001) and psychiatric morbidities (21.7% vs 10.1%, p=0.019) than those without IBS. Anthropometrics, metabolic and hormonal profiles were similar between PCOS women with and without IBS. Among women with PCOS, those with both IBS and obesity had the highest risk of developing sleep difficulties (odds ratio: 5.91; 95% confidence interval: 1.77-19.77) and psychiatric distress (odds ratio: 4.39; 95% confidence interval: 1.26-15.29) than those without. Conclusion: Women with PCOS have increased IBS, obesity, sleep and psychiatric disturbances. The presence of IBS in PCOS women is associated with sleep and psychiatric disorders. The coexistence of obesity and IBS exacerbates sleep difficulties and psychiatric distress. Screening and management of IBS and obesity might be warranted to improve sleep and psychiatric disturbances in women with PCOS.

Wei Chang An pill regulates gastrointestinal motility in a bidirectional manner.

CONTEXT: Wei Chang An (WCA) is a commercial prescription developed for the coordination of gastrointestinal movement. OBJECTIVE: To investigate the role of WCA in the regulation of diarrhoea and constipation in rats. MATERIAL AND METHODS: The diarrhoea and constipation models were prepared by gavage of Folium senna and diphenoxylate hydrochloride. Rats were randomized equally (n = 6) into the normal group given saline daily, the positive group given Pinaverium Bromide (13.5 mg/kg) or Sennoside A (0.1 mg/kg) and three WCA-treated groups (22, 44, and 88 mg/kg) by gavage daily for 7 consecutive days. The effects of WCA were assessed by a series of faecal symptoms and histopathology. Gastrointestinal parameters were determined by ELISA. The effect of WCA on gastrointestinal tissues was evaluated by strip assay. Expression of ROCK-1 and MLCK was measured by RT-PCR and Western blotting. RESULTS: Data from Bristol stool form scale, diarrhoea index, visceral sensitivity, defaecation time, and intestinal propulsive rate showed that WCA protected rats against diarrhoea and constipation (p < 0.01). The up-regulation of Substance P and 5-hydroxytryptamine in diarrhoea rats and down-regulation of Substance P and vasoactive intestinal polypeptide in constipation rats were inhibited by WCA (p < 0.05). WCA stimulated the gastrointestinal strip contractions but inhibited ACh-induced contractions (p < 0.01). The decreased ROCK-1 and MLCK expression in diarrhoea rats and increased in constipation rats were suppressed by WCA (p < 0.01). CONCLUSIONS: WCA has both antidiarrhea and anti-constipation effects, suggesting its bidirectional role in gastrointestinal modulation, and providing evidence of WCA for irritable bowel syndrome treatment.

Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders.

Migraine, the leading cause of disability in the population aged below 50, is associated with functional gastrointestinal (GI) disorders (FGIDs) such as functional nausea, cyclic vomiting syndrome, and irritable bowel syndrome (IBS). Conversely, changes in intestinal GI transit may cause diarrhea or constipation and are a component of the autonomic symptoms associated with pre- and post-dorsal phases of migraine attack. These mutual relationships provoke a question on a common trigger in migraine and FGIDs. The kynurenine (l-kyn) pathway (KP) is the major route for l-tryptophan (l-Trp) metabolism and transforms l-Trp into several neuroactive compounds. Changes in KP were reported in both migraine and FGIDs. Migraine was largely untreatable, but several drugs approved lately by the FDA, including monoclonal antibodies for calcitonin gene-related peptide (CGRP) and its receptor, create a hope for a breakthrough in migraine treatment. Derivatives of l-kyn were efficient in pain relief with a mechanism including CGRP inhibition. KP products are important ligands to the aryl hydrocarbon receptor (AhR), whose activation is implicated in the pathogenesis of GI and migraine. Toll-like receptors (TLRs) may play a role in migraine and IBS pathogeneses, and KP metabolites detected downstream of TLR activation may be an IBS marker. The TLR4 signaling was observed in initiating and maintaining migraine-like behavior through myeloid differentiation primary response gene 88 (MyD88) in the mouse. The aim of this review is to justify the view that KP modulation may provide common triggers for migraine and FGIDs with the involvement of TLR, AhR, and MyD88 activation.

Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain.

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis-a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

[The new guideline on irritable bowel syndrome: what is new?] / Die neue Leitlinie zum Reizdarmsyndrom: Was ändert sich?

IRRITABLE BOWEL SYNDROME: WHAT IS NEW?: The following refers only to irritable bowel syndrome (IBS) in adults. The new guideline includes a separate section on IBS for paediatric patients. Irritable bowel syndrome (IBS) presents as a heterogeneous picture with chronic abdominal complaints related to the bowel. These are usually accompanied by changes in bowel movements and lead to impaired quality of life. The genesis is multifactorial and there are complex underlying pathophysiological mechanisms associated with IBS. Thus, disturbances in various components of the gut-brain axis and the increasing importance of the microbiome can be identified. Various psychological comorbidities also play a role. DIAGNOSTICS: The diagnosis is made by a thorough anamnesis and symptom-oriented exclusion of important differential diagnoses. A subdivision into different subtypes depending on the main symptoms is beneficial for the further management of IBS patients. The diagnosis of IBS should be made as early as possible after reliable exclusion of the important differential diagnoses. If diarrhoea dominates as a symptom, a detailed differential diagnosis and functional diagnosis should be carried out. THERAPY: There is no proven causal and no established standard therapy. Due to the variable genesis and symptom manifestation of IBS, a broad spectrum of therapy options results, whereby there is no individual prediction regarding effectiveness and therefore every therapy is initially probationary. Symptom-independent general therapies that can be used for all subtypes include dietary methods (e. g. the low-FODMAP diet), probiotics, psychotherapy methods and complementary medicine. The choice of symptom-dependent drug treatments is made according to the subtype/main symptom. In the case of diarrhoea, bile acid binders, the non-absorbable antibiotic rifaximin or, in individual cases, 5-HT3-antagonists can be used in addition to loperamide. In constipation, prucalopride and linaclotide have value in addition to the use of soluble fibre and macrogol/other laxatives. For abdominal pain/cramps, studies show good results for spasmolytics, especially peppermint oil, and for tricyclic-type antidepressants. For the main symptom of flatulence, probiotics, rifaximin and especially the low-FODMAP diet can show positive results in studies.