Serotonin transporter and cholecystokinin in diarrhea-predominant irritable bowel syndrome: Associations with abdominal pain, visceral hypersensitivity and psychological performance

BACKGROUND Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome(IBS).Previous studies have found that cholecystokinin(CCK)can enhance colon movement and that serotonin transporter(SERT)is a transmembrane transport protein with high affinity for 5-hydroxytryptamine,which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity.We speculate that SERT and CCK might play a role in the pathogenesis of diarrheapredominant IBS(IBS-D)by affecting visceral sensitivity and the brain-gut axis.AIM To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain,visceral hypersensitivity and psychological performance.METHODS This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls.The severity of abdominal pain,visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls,the levels of SERT and CCK in plasma and colonic mucosa were evaluated,and the correlations between them were analyzed.RESULTS There were significant differences in the initial sensation threshold(31.00±8.41 mL vs 52.22±8.09 mL,P<0.001),defecating sensation threshold(51.75±13.57 mL vs 89.44±8.73 mL,P<0.001)and maximum tolerable threshold(97.25±23.64 mL vs 171.11±20.83 mL,P<0.001)between the two groups.IBS-D patients had more severe anxiety(7.78±2.62 vs 2.89±1.02,P<0.001)and depressive(6.38±2.43 vs 2.06±0.73,P<0.001)symptoms than healthy controls.Significant differences were also found in mucosal CCK(2.29±0.30 vs 1.66±0.17,P<0.001)and SERT(1.90±0.51 vs 3.03±0.23,P<0.001)between the two groups.There was a significant positive correlation between pain scores and mucosal CCK(r=0.96,0.93,0.94,P<0.001).Significant negative correlations between anxiety(r=-0.98;P<0.001),depression(r=-0.99;P<0.001),pain evaluation(r=-0.96,-0.93,-0.95,P<0.001)and mucosal SERT were observed.CONCLUSION IBS-D patients had psychosomatic disorders and visceral hypersensitivity.SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the braingut axis and affecting visceral sensitivity.This provides a new potential method for identifying a more specific and effective therapeutic target.

Family history of irritable bowel syndrome is the major determinant of persistent abdominal complaints in young adults with a history of pediatric recurrent abdominal pain

AIM： To assess the late outcome of teen-agers with a previous history of recurrent abdominal pain （RAP） or irritable bowel syndrome （IBS）. METHODS： A group of 67 children with RAP referred to the department from January 1986 to December 1995 was followed up between 5 and 13 years after the initial diagnosis by means of a structured telephone interview. We hypothesized that those patients with persistent adult IBS-like symptoms would be significantly more likely to report a family history oflBS in comparison with adults with no persistent abdominal complaint. RESULTS： Out of the 52 trackable subjects, 15 were found to present IBS-like symptoms at follow-up （29%） whereas the majority （37 subjects） did not. Subjects with IBS-like symptoms were almost three times more likely to present at least one sibling with similar symptoms compared to subjects not complaining （40.0% vs 16.0%）, respectively （P 〈 0.05 at Student t test）. Subjects with IBS-like symptoms also reported a higher prevalence of extra-intestinal symptoms, such as back pain, fibromyalgia, headache, fatigue and sleep disturbances. CONCLUSION： The study confirms previous observations indicating that pediatric RAP can predict later development of IBS. The latter appears to be greatly influenced by intrafamilial aggregation of symptoms, possibly through the learning of a specific illness behavior.

Intermittent abdominal pain accompanied by defecation difficulties caused by Chilaiditi syndrome: A case report

We report a case of intermittent lower abdominal pain and distension accompanied by defecation difficulties for 3 years due to Chilaiditi syndrome in a 59-yearold male. Before admission to our hospital, the patient had undergone gastroscopy, which showed gastritis and duodenitis, and colonoscopy, which showed cecum deformation and cicatricial changes of the mucous membrane in the colon hepatic flexure. A computed tomography(CT) scan of the abdomen at our hospital confirmed right hepatic atrophy and interposition of the colon. Moreover, CT simulation endoscopy identified cystic dilatation in the colon hepatic flexure with the widest diameter of 8.2 cm. The patient was diagnosed with Chilaiditi syndrome. As the patient was unable to endure his defecation difficulties, he underwent a laparoscope-assisted right hemicolectomy. The patient had a good recovery. During the follow-up period of 9 mo, the patient remained symptom-free.

Are bowel symptoms and psychosocial features different in irritable bowel syndrome patients with abdominal discomfort compared to abdominal pain?

BACKGROUND The Rome IV criteria eliminated abdominal discomfort for irritable bowel syndrome(IBS), which was previously included in Rome III. There are questions as to whether IBS patients with abdominal discomfort(seen in Rome III but not Rome IV) are different from those with abdominal pain(Rome IV).AIM To compare bowel symptoms and psychosocial features in IBS patients diagnosed with Rome III criteria with abdominal discomfort, abdominal pain, and pain &discomfort.METHODS We studied IBS patients meeting Rome III criteria. We administered the IBS symptom questionnaire, psychological status, and IBS quality of life. Patients were classified according to the predominant abdominal symptom associated with defecation into an only pain group, only discomfort group, and pain & discomfort group. We compared bowel symptoms, extraintestinal symptoms, IBS quality of life, psychological status and healthcare-seeking behaviors, and efficacy among the three groups. Finally, we tested risk factors for symptom reporting in IBS patients.RESULTS Of the 367 Rome III IBS patients enrolled, 33.8%(124 cases) failed to meet Rome IV criteria for an IBS diagnosis. There were no meaningful differences between the pain group(n = 233) and the discomfort group(n = 83) for the following:(1) Frequency of defecatory abdominal pain or discomfort;(2) Bowel habits;(3) Coexisting extragastrointestinal pain;(4) Comorbid anxiety and depression;and(5) IBS quality of life scores except more patients in the discomfort group reported mild symptom than the pain group(22.9% vs 9.0%). There is a significant tendency for patients to report their defecatory and non-defecatory abdominal symptom as pain alone, or discomfort alone, or pain & discomfort(all P < 0.001).CONCLUSION IBS patients with abdominal discomfort have similar bowel symptoms and psychosocial features to those with abdominal pain. IBS symptoms manifesting abdominal pain or discomfort may primarily be due to different sensation and reporting experience.

Postpolypectomy syndrome without abdominal pain led to sepsis/septic shock and gastrointestinal bleeding:A case report

BACKGROUND Postpolypectomy syndrome(PPS)is a rare postoperative complication of colonic polypectomy.It presents with abdominal pain and fever accompanied by coagulopathy and elevated inflammatory markers.Its prognosis is usually good,and it only requires outpatient treatment or observation in a general ward.How-ever,it can be life-threatening.CASE SUMMARY The patient was a 58-year-old man who underwent two colonic polypectomies,each resulting in life-threatening sepsis,septic shock,and coagulopathy.Each of the notable manifestations was a rapid drop in blood pressure,an increase in heart rate,loss of consciousness,and heavy sweating,accompanied by shortness of breath and decreased oxygen in the finger pulse.Based on the criteria of organ dysfunction due to infection,we diagnosed him with sepsis.The patient also experienced severe gastrointestinal bleeding after the second operation.Curiously,he did not complain of any abdominal pain throughout the course of the illness.He had significantly elevated concentrations of inflammatory markers and coagulopathy.Except for the absence of abdominal pain,his fever,significant coagulopathy,and elevated inflammatory marker concentrations were all consistent with PPS.Abdominal computed tomography and superior mesenteric artery computed tomography angiography showed no free air or vascular damage.Thus,the diagnosis of colon perforation was not considered.The final blood culture results indicated Moraxella osloensis.The patient was transferred to the intensive care unit and quickly improved after fluid resuscitation,antibiotic treatment,oxygen therapy,and blood transfusion.CONCLUSION PPS may induce dysregulation of the systemic inflammatory response,which can lead to sepsis or septic shock,even in the absence of abdominal pain.

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 IBSlike symptoms.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

Efficacy and tolerability of chitin-glucan combined with simethicone(GASTRAP^(■)DIRECT)in irritable bowel syndrome:A prospective,open-label,multicenter study

BACKGROUND Irritable bowel syndrome(IBS),defined according to the Rome IV diagnostic criteria,is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel habits.First-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic gain.GASTRAP^(■)DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action.AIM To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with IBS.METHODS In this prospective,multicenter,open-label trial,120 patients with IBS received three sticks of GASTRAP^(■)DIRECT(1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone)per day for 4 weeks.The primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)4.The analysis was performed using the per-protocol set.Cardinal symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were evaluated.RESULTS Overall,100 patients were evaluated.At W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,P<0.0001).Similar improvements were observed for bloating[8.0±1.7 vs 4.7±2.9,P<0.0001;60%(95%CI:50-70)responders],abdominal distension[7.2±2.1 vs 4.4±3.1,P<0.0001;53%(95%CI:43-63)responders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,P<0.0001;54%(95%CI:44-64)responders].Stool consistency improved in most patients(90%and 57%for patients with liquid and hard stools,respectively).Overall,42%of patients with defecatory disorders reported very much/considerable improvements by W2.No severe adverse event occurred,and tolerability was rated“good”or“very good”by 93%of patients.CONCLUSION GASTRAP^(■)DIRECT is safe and well tolerated,alleviating IBS symptoms rapidly in 2 weeks.This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.

Symptoms and Their Interpretation in Patients Self-Treating Abdominal Cramping and Pain with a Spasmolytic(Butylscopolamine Bromide)—A Pharmacy-Based Survey

Background: A majority of people suffering from functional abdominal complaints treat themselves with OTC medication. Aim: To gain information on symptoms and their interpretation in patients self-treating abdominal cramping and pain with a spasmolytic (butylscopolamine). Method: 4,680 questionnaires were distributed by 306 pharmacists in Germany to patients suffering from abdominal complaints and buying butylscopolamine. Key findings: Questionnaires from 1,539 respondents were returned, and 1,417 could be evaluated. Abdominal cramping was the major reason for buying butylscopolamine. Only a minority of respondents had consulted a general practitioner (27.3%) and even less a specialist (12.5%). Only a minority of subjects met expert criteria for irritable bowel syndrome (13%). There was a large overlap between self-reported dysmenorrhoea and bowel symptoms (35%). Conclusions: Real life conditions do not seem to be well covered by expert criteria. Differentiating bowel origin from uterine origin in pelvic pain syndromes seems especially problematic. This may particularly apply to the OTC market.

Irritable bowel syndrome in children:Current knowledge, challenges and opportunities

Irritable bowel syndrome(IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their families and poses a significant burden on healthcare systems. Standard symptom-based criteria for diagnosis of pediatric IBS have changed several times during the past two decades and there are some differences in interpreting symptoms between different cultures. This has posed a problem when using them to diagnose IBS in clinical practice. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. A few potential therapeutic modalities have been tested in children and only a small number of them have shown some benefit. In addition, most of the described patho-physiological mechanisms and treatment options are based on adult studies. These have surfaced as challenges when dealing with pediatric IBS and they need to be overcome for effective management of children with IBS. Recently suggested top-down and bottom-up models help integrating reported patho-physiological mechanisms and will provide an opportunity for better understanding of the diseases process. Treatment trials targeting single treatment modalities are unlikely to have clinically meaningful therapeutic effects on IBS with multiple integrating patho-physiologies. Trials focusing on multiple combined pharmacological and non-pharmacological therapies are likely to yield more benefit. In addition to treatment, in the future, attention should be paid for possible prevention strategies for IBS.

Irritable bowel syndrome in children: Pathogenesis, diagnosis and evidence-based treatment

Irritable bowel syndrome (IBS) is the commonest cause of recurrent abdominal pain (RAP) in children in both more developed and developing parts of the world. It is defined by the Rome III criteria for functional gastrointestinal disorders. It is characterized by abdominal pain that is improved by defecation and whose onset is associated with a change in stool form and or frequency and is not explained by structural or biochemical abnormalities. It is estimated that 10%-15% of older children and adolescents suffer from IBS. IBS can be considered to be a brain-gut disorder possibly due to complex interaction between environmental and hereditary factors. The diagnosis of IBS is made based on the Rome III criteria together with ruling out organic causes of RAP in children such as inflammatory bowel disease and celiac disease. Once the diagnosis of IBS is made, it is important to explain to the parents (and children) that there is no serious underlying disease. This reassurance may be effective treatment in a large number of cases. Lifestyle modifications, stress management, dietary interventions and probiotics may be beneficial in some cases. Although there is limited evidence for efficacy of pharmacological therapies such as antispasmodics and antidiarrheals; these have a role in severe cases. Biopsychosocial therapies have shown encouraging results in initial trials but are beset by limited availability. Further research is necessary to understand the pathophysiology and provide specific focused therapies.

Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

Irritable bowel syndrome(IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.

Irritable bowel syndrome symptom severity improves equally with probiotic and placebo

AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome(IBS) symptoms and quality of life(Qo L).METHODS In this randomized triple-blind trial, adult IBS volunteerswho were recruited according to Rome Ⅲ criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score(IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk runin period, after 4 and 12 wk of intervention, and after a 4-wk washout.RESULTS A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline(VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively(P value for placebo vs combined active doses = 0.0460).CONCLUSION NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.

Effi cacy of tricyclic antidepressants in irritable bowel syndrome:A meta-analysis

We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.

Need for a comprehensive medical approach to the neuroimmuno-gastroenterology of irritable bowel syndrome

Irritable bowel syndrome （IBS） is defined by the Rome ]I[ criteria as symptoms of recurrent abdominal pain or discomfort with the onset of a marked change in bowel habits with no evidence of an inflammatory, anatomic, metabolic, or neoplastic process. As such, many clinicians regard IBS as a central nervous system problem of altered pain perception. Here, we review the recent literature and discuss the evidence that supports an organic based model, which views IBS as a complex, heterogeneous, inter-dependent, and multi-variable inflammatory process along the neuronal-gut axis. We delineate the organic pathophysiology of IBS, demonstrate the role of inflammation in IBS, review the possible differences between adult and pediatric IBS, discuss the merits of a comprehensive treatment model as taught by the Institute of Functional Medicine, and describe the potential for future research for this syndrome.

Clinical outcome of Fitz-Hugh-Curtis syndrome mimicking acute biliary disease

AIM: To analyze the clinical characteristics of patients diagnosed with Fitz-Hugh-Curtis syndrome.METHODS: The clinical courses of patients that visited St. Mary's Hospital with abdominal pain from January 2005 to December 2006 and were diagnosed with Fitz-Hugh-Curtis syndrome were examined.RESULTS: Fitz-Hugh-Curtis syndrome was identified in 22 female patients of childbearing age; their mean age was 31.0 ± 8.1 years. Fourteen of these cases presented with pain in the upper right abdomen alone or together with pain in the lower abdomen, and six patients presented with pain only in the lower abdomen. The first impression at the time of visit was acute cholecystitis or cholangitis in 10 patients and acute appendicitis or pelvic inflammatory disease in eight patients. Twenty-one patients were diagnosed by abdominal computer tomograghy (CT), and the results of abdominal sonography were normal for 10 of these patients. Chlamydia trichomatis was isolated from 18 patients. Two patients underwent laparoscopic adhesiotomy and 20 patients were completely cured by antibiotic treatment.CONCLUSION: For women of childbearing age with acute pain in the upper right abdomen alone or together with pain in the lower abdomen, Fitz-Hugh-Curtis syndrome should be considered during differential diagnosis. Moreover, in cases suspected to be Fitz-Hugh-Curtis syndrome, abdominal CT, rather than abdominal sonography, assists in the diagnosis.

Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis

AIMTo confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management.METHODSAn individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline (&#x0201c;IBS-C &#x02265; 2 subpopulation&#x0201d;).RESULTSS. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C &#x02265; 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as &#x0201c;normal&#x0201d; compared to Placebo (respectively 3.13 &#x000b1; 1.197 a.u. vs 2.58 &#x000b1; 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C &#x02265; 2 subpopulation (Active group: 3.14 &#x000b1; 1.219 a.u. vs Placebo group: 2.59 &#x000b1; 1.017 a.u., P = 0.0009).CONCLUSIONThis meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C &#x02265; 2 subpopulations.

High risk of temporomandibular disorder in irritable bowel syndrome: Is there a correlation with greater illness severity?

AIMTo investigate the prevalence and the risk of temporomandibular disorders (TMDs) in patients with irritable bowel syndrome (IBS) (including each subtype: constipation, diarrhoea, and mixed) compared to the general population.METHODSBetween January 2014 and December 2015 we enrolled consecutively adult patients diagnosed with IBS at the outpatient clinic of the University of Salerno and healthy controls (HC) without IBS. At enrollment, we analyzed all patients for the presence of TMDs according to the Research Diagnostic Criteria for TMD.RESULTSWe enrolled 91 IBS patients (23 IBS-D, 30 IBS-C and 38 IBS-M) and 57 HC in the study. We found a higher risk of having TMD (OR = 3.41, 95%CI: 1.66-7.01) compared to the HC. The risk of having TMD was independent of IBS-subtype. Multiple regression analysis showed that facial pain was positively related to abdominal pain and higher level of depression.CONCLUSIONIBS patients had a more than three times greater risk of TMD compared to HC. The risk of having TMD was similar in different IBS subtypes. IBS patients that also fulfilled criteria for TMD seem to share along with chronic facial and abdominal pain a significant co-occurrence with psychiatric disorders and female preponderance.

Effect of Bifidobacterium longum 35624 on disease severity and quality of life in patients with irritable bowel syndrome

BACKGROUND Bifidobacterium longum 35624 has shown efficacy in improving irritable bowel syndrome(IBS)symptoms compared with placebo in double-blind randomized studies.However,few data are available from real-life clinical practice or from studies that used Rome IV criteria to diagnose IBS.AIM To assess the effect of B.longum 35624 on IBS severity and quality of life in a reallife setting.METHODS From November 2018 to January 2020,278 patients with IBS(according to Rome IV criteria)were enrolled in a prospective,open-label,multicenter observational study by private practice gastroenterologists to received one capsule of B.longum 35624(10^(9) colony-forming units)per day for 30 d.Participation in the study was independently proposed to patients during spontaneous consultations.Disease severity(assessed by the IBS severity scoring system)and patient quality of life(assessed by the IBS quality of life questionnaire)were compared between the inclusion visit(baseline)and the visit at the end of 30 d of treatment.The characteristics of patients were described at baseline.Continuous variables comparisons between inclusion and end-of-treatment visits were performed using the t-test and Kruskal-Wallis test.Categorical variables comparisons were performed using theχ^(2) test.RESULTSA total of 233 patients,with a mean age of 51.4 years and composed of 71.2%women,were included in the study.Of these patients,48.1%had moderate IBS and 46.4%had severe IBS.After a 30-d treatment period with one B.longum 35624 capsule per day,a significant decrease in IBS severity was observed compared to baseline(mean±SD,IBS severity scoring system scores:208±104 vs 303±81,P<0.001)and 57%of patients moved to lower severity categories or achieved remission.The quality of life of patients was also improved by the treatment(IBS Quality of Life questionnaire score:68.8±20.9 vs 60.2±20.5;P<0.001)and 63.8%of patients were satisfied with the treatment.CONCLUSION Thirty days of treatment with B.longum 35624 reduces disease severity and improves the quality of life of patients with IBS,particularly those with the most severe forms of IBS.

Clinical trial:Lactobacillus plantarum 299v(DSM 9843)improves symptoms of irritable bowel syndrome

AIM:To assess the symptomatic efficacy of Lactobacillus plantarum 299v(L.plantarum 299v)(DSM 9843) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome(IBS) patients fulfilling the Rome Ⅲ criteria.METHODS:In this double blind,placebo-controlled,parallel-designed study,subjects were randomized to daily receive either one capsule of L.plantarum 299v(DSM 9843) or placebo for 4 wk.Frequency and intensity of abdominal pain,bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated.RESULTS:Two hundred and fourteen IBS patients were recruited.After 4 wk,both pain severity(0.68 + 0.53 vs 0.92 + 0.57,P < 0.05) and daily frequency(1.01 + 0.77 vs 1.71 + 0.93,P < 0.05) were lower with L.plantarum 299v(DSM 9843) than with placebo.Similar results were obtained for bloating.At week 4,78.1 % of the patients scored the L.plantarum 299v(DSM 9843) symptomatic effect as excellent or good vs only 8.1 % for placebo(P < 0.01).CONCLUSION:A 4-wk treatment with L.plantarum 299v(DSM 9843) provided effective symptom relief,particularly of abdominal pain and bloating,in IBS patients fulfilling the Rome Ⅲ criteria.