Functional gastrointestinal disorders in inflammatory bowel disease: Time for a paradigm shift?

Recent advances in biological therapies have revolutionalised and redefined treatment targets in inflammatory bowel disease(IBD).There is now a stronger emphasis on achieving the more stringent therapeutic goals of mucosal and histological healing,rather than clinical remission alone.Consequently,the treatment of refractory“functional”gastrointestinal symptoms,often attributed as the aftermath of previous inflammation,has recently become more prominent in quiescent disease.With further expected advances in anti-inflammatory treatments on the horizon,the burden of such symptoms in quiescent disease,which have been relatively neglected,is set to become an even bigger problem.In this article,we highlight the current state of research and understanding in this field,including recent developments and clinical practice guidelines on the diagnosis and management of functional gastrointestinal symptoms,such as irritable bowel syndrome and functional anorectal and pelvic floor disorders,in patients with quiescent IBD.These disorders are not only highly prevalent in these patients,they are often misdiagnosed,and are difficult to treat,with very few evidence-based therapies.Moreover,they are associated with substantial impairment in quality-of-life,considerable morbidity,and psychological distress.There is therefore an urgent need for a change in emphasis towards earlier recognition,positive diagnosis,and targeted treatment for patients with ongoing functional gastrointestinal symptoms in the absence of active IBD.This article also highlights the need for further research to develop much needed evidence-based therapies.

Prevalence of functional gastrointestinal disorders in children with celiac disease on different types of gluten-free diets

BACKGROUND Functional gastrointestinal disorders(FGIDs)are common during the pediatric age.FGIDs are not related to biochemical or structural abnormalities.However,since they have a high prevalence,several studies have evaluated an overlap between FGIDs and organic diseases.Individuals with celiac disease(CD)have been shown to be at an increased risk for functional abdominal pain,even if they adhere well to a gluten-free diet(GFD).Little information is available for the pediatric age group.The aims of our study were to evaluate the prevalence of FGIDS in CD children 1 year after diagnosis and to compare the prevalence of FGIDs in CD children on a GFD with processed foods compared with those on a GFD with natural products.AIM To assess the prevalence of FGIDs in children with CD after 1 year of follow-up and to compare the prevalence of FGIDs in children with CD on a GFD with processed foods and in children on a GFD with natural products.METHODS We recruited pediatric patients aged 1-18 years with a new CD diagnosis.Participants were randomized to two groups:Group A on a GFD with processed foods(diet 1);and group B on a GFD with natural products(diet 2).Clinical monitoring,diet assessment and the questionnaire on pediatric gastrointestinal symptoms-Rome IV version were performed at diagnosis(T0)and after 12 mo of follow-up(T1).Dietary intake was assessed using a 3-d food diary record.Data from the diaries were evaluated using WinFood nutrient analysis software.We assessed the prevalence of FGIDs at T1 and the correlation with the type of GFD.RESULTS We registered 104 CD children,with 55 patients in group A(53.0%)and 49 patients in group B(47.0%).Initially,30 of the 55(54.5%)CD children were symptomatic in group A,while 25 of 49(51.0%)were symptomatic in group B.At T1,in spite of a low or negative serology for CD,FGIDs prevalence was 10/55(18.0%)in group A and 8/49(16.3%)in group B,with no statistically significant difference between the two groups(P=0.780).At T1 the macro-and micronutrient intake was similar across the two groups with no significant differences in nutrient analysis.However,in both groups at T1 we found that a lower prevalence of FGIDs(P=0.055)was associated with an inferior caloric(odds ratio=0.99,95%confidence interval:0.99-1.00)and fat(odds ratio=0.33,95%confidence interval:0.65-0.95)intake.CONCLUSION Our results showed that CD children on a GFD have gastrointestinal symptoms with an elevated prevalence of FGIDs.Our study suggests that developing FGIDs may be linked to caloric intake and percentage of food fat,but it does not change between a GFD with processed foods or a GFD with natural products.However,long-term monitoring is required to evaluate a correlation between FGIDs and various types of GFDs.

Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Functional gastrointestinal disorders,mental health,genetic susceptibility,and incident chronic kidney disease

Background:Whether functional gastrointestinal disorders(FGIDs)are associated with the long-term risk of chronic kidney disease(CKD)remains unclear.We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods:About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included.Participants with FGIDs(including irritable bowel syndrome[IBS],dyspepsia,and other functional intestinal disorders[FIDs;mainly composed of constipation])were the exposure group,and non-FGID participants were the non-exposure group.The primary outcome was incident CKD,ascertained from hospital admission and death registry records.A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD,and the mediation analysis was performed to investigate the mediation proportions of mental health.Results:At baseline,33,156(8.0%)participants were diagnosed with FGIDs,including 21,060(5.1%),8262(2.0%),and 6437(1.6%)cases of IBS,dyspepsia,and other FIDs,respectively.During a mean follow-up period of 12.1 years,11,001(2.6%)participants developed CKD.FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs(hazard ratio[HR],1.36;95%confidence interval[CI],1.28-1.44).Similar results were observed for IBS(HR,1.27;95%CI,1.17-1.38),dyspepsia(HR,1.30;95%CI,1.17-1.44),and other FIDs(HR,1.60;95%CI,1.43-1.79).Mediation analyses suggested that the mental health score significantly mediated 9.05%of the association of FGIDs with incident CKD and 5.63-13.97%of the associations of FGID subtypes with CKD.Specifically,the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion:Participants with FGIDs had a higher risk of incident CKD,which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Attention deficit hyperactivity disorder and gastrointestinal morbidity in a large cohort of young adults

BACKGROUND Although the association of attention deficit hyperactivity disorder(ADHD)with psychiatric disorders is well known,its association with somatic diseases is unclear.Only few studies have investigated the gastrointestinal(GI)morbidity in adult patients with ADHD.AIM To measure gastrointestinal comorbidity and its burden on healthcare in young adults with ADHD.METHODS The cohort included subjects aged 17-35 years recruited to the Israel Defense Forces in 2007-2013,33380 with ADHD and 355652 without(controls).The groups were compared for functional and inflammatory conditions of the gastrointestinal tract and clinic and specialist visits for gastrointestinal symptoms/disease during service(to 2016).Findings were analyzed by generalized linear models adjusted for background variables.RESULTS Compared to controls,the ADHD group had more diagnoses of functional gastrointestinal disorders(referred to as FGID),namely,dyspepsia[odds ratio(OR):1.48,95%confidence interval(CI):1.40-1.57,P<0.001],chronic constipation(OR:1.64,95%CI:1.48-1.81,P<0.001),and irritable bowel syndrome(OR:1.67,95%CI:1.56-1.80,P<0.001)but not of organic disorders(inflammatory bowel disease,celiac disease).They had more frequent primary care visits for gastrointestinal symptoms[rate ratio(RR):1.25,95%CI:1.24-1.26,P<0.001]and referrals to gastrointestinal specialists(RR:1.96,95%CI:1.88-2.03,P<0.001)and more episodes of recurrent gastrointestinal symptoms(RR:1.29,95%CI:1.21-1.38,P<0.001).Methylphenidate use increased the risk of dyspepsia(OR:1.49,95%CI:1.28-1.73,P<0.001)and constipation(OR:1.42,95%CI:1.09-1.84,P=0.009).CONCLUSION ADHD in young adults is associated with an excess of FGID and increased use of related health services.Research is needed to determine if an integrative approach treating both conditions will benefit these patients and cut costs.

Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder

AIM To study if anxiety, depression and experience of stress are associated with gastrointestinal(GI) symptoms in patients with bipolar disorder.METHODS A total of 136 patients with bipolar disorder(mean age 49.9 years; 61% women) and 136 controls from the general population(mean age 51.0 years; 60% women) were included in the study. GI symptoms were assessed with The Gastrointestinal Symptom Rating Scale-irritable bowel syndrome(GSRS-IBS), level of anxiety and depression with The Hospital Anxiety and Depression Scale(HADS) and stress-proneness with Perceived Stress Questionnaire. Over a ten year period, all visits in primary care were retrospectively recorded in order to identify functional GI disorders.RESULTS In subjects with low total HADS-score, there were no significant differences in GI-symptoms between patients and controls(GSRS-IBS 7.0 vs 6.5, P = 0.513). In the patients with bipolar disorder there were significant correlations between all GSRS and HADS subscores for all symptom clusters except for "constipation" and "reflux". Factors associated to GI symptoms in the patient group were female sex(adjusted OR = 2.37, 95%CI: 1.07-5.24) and high HADS-Depression score(adjusted OR = 3.64, 95%CI: 1.07-12.4). These patients had also significantly more visits for IBS than patients with low HADS-Depression scores(29% vs 8%, P = 0.008). However, there was no significant differences in consulting behaviour for functional GI disorders between patients and controls(25% vs 17%, P = 0.108).CONCLUSION Female patients and patients with high HADS depression score reported significantly more GI symptoms, whereas patients with low HADS scores did not differ from control subjects.

Cow’s milk-induced gastrointestinal disorders:From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders.Cow’s milk protein allergy(CMPA)is the most common food allergy,especially in infancy and childhood,which may persist into adulthood.There are three main types of CMPA;immunoglobulin E(IgE)-mediated CMPA,non-IgEmediated CMPA,and mixed type.CMPA appears before the first birthday in almost all cases.Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis.CMPA(often non-IgE mediated)can present with symptoms of gastroesophageal reflux,eosinophilic esophagitis,hemorrhagic gastritis,food protein-induced protein-losing enteropathy,and food protein-induced enterocolitis syndrome.Most CMPAs are benign and outgrown during childhood.CMPA is not as common in adults as in children,but when present,it is usually severe with a protracted course.Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose.Lactose intolerance has four typical types:Developmental,congenital,primary,and secondary.Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults.They are also common in inflammatory bowel diseases.Milk consumption may have preventive or promoter effects on cancer development.Milk may also become a source of microbial infection in humans,causing a wide array of diseases,and may help increase the prevalence of antimicrobial resistance.This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.

Evaluating the efficacy of endoscopic sphincterotomy on biliary-type sphincter of Oddi dysfunction: A retrospective clinical trial

BACKGROUND Although endoscopic sphincterotomy(EST)has a positive therapeutic effect on biliary-type sphincter of Oddi dysfunction(SOD),some patients still have little relief after EST,which implies that other functional abdominal pain may also be present with biliary-type SOD and interfere with the diagnosis and treatment of it.AIM To retrospectively assess EST as a treatment for biliary-type SOD and analyze the importance of functional gastrointestinal disorder(FGID)in guiding endoscopic treatment of SOD.METHODS Clinical data of 79 patients with biliary-type SOD(type I and type II)treated with EST at Affiliated Hospital of Guizhou Medical University from January 2014 to January 2019 were retrospectively collected to evaluate the clinical therapeutic effect of EST.The significance of relationship between FGID and biliary-type SOD was analyzed.RESULTS Seventy-nine patients with biliary-type SOD received EST,including 29 type 1 patients and 50 type 2 patients.The verbal rating scale-5(VRS-5)scores before EST were all 3 or 4 points,and the scores decreased after EST;the difference was statistically significant(P<0.05).After EST,the serum indexes of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin in biliary-type SOD were significantly lower than before(P<0.05).After EST,67(84.8%)and 8(10.1%)of the 79 patients with biliary-type SOD had obviously effective(VRS-5=0 points)and effective treatment(VRS-5=1-2 points),with an overall effectiveness rate of 94.9%(75/79).There was no difference in VRS-5 scores between biliary-type SOD patients with or without FGID before EST(P>0.05).Of 12 biliary-type SOD(with FGID)patients,11 had abdominal pain after EST;of 67 biliary-type SOD(without FGID)patients,0 had abdominal pain after EST.The difference was statistically significant(P<0.05).The 11 biliary-type SOD(with FGID)patients with recurrence of symptoms,the recurrence time was about half a year after the EST,and the symptoms were significantly relieved after regular medical treatment.There were 4 cases of postendoscopic retrograde cholangiopancreatography pancreatitis(5.1%),and no cholangitis,bleeding or perforation occurred.Patients were followed up for 1 year to 5 years after EST,with an average follow-up time of 2.34 years,and there were no long-term adverse events such as sphincter of Oddi restenosis or cholangitis caused by intestinal bile reflux during the follow-up.CONCLUSION EST is a safe and effective treatment for SOD.For patients with type I and II SOD combined with FGID,single EST or medical treatment has limited efficacy.It is recommended that EST and medicine be combined to improve the cure rate of such patients.

Gastrointestinal symptoms in acromegaly:A case control study

BACKGROUND Acromegaly is a chronic disease caused by a pituitary somatotroph adenoma resulting in excess secretion of growth hormone,which leads to excess secretion of Insulin like growth factor 1 from the liver,causing abnormal soft tissue growth.There is increasing awareness that diseases affecting connective tissue are associated with an increase in functional gastrointestinal symptoms.Data was collected from patients with a confirmed diagnosis of acromegaly to evaluate the intensity,variety and impact of abdominal symptoms in comparison with a control group who were healthy participants recruited from the local fracture clinic.AIM To evaluate the frequency type and burden of abdominal symptoms in acromegaly in comparison with a control group.METHODS Medical documentation of patients with a diagnosis of acromegaly treated in one tertiary medical centre between 2010 and 2017 has been analysed.Data was collected from patients with confirmed acromegaly,using the Short Form Health Survey(SF36)and Rome IV Diagnostic questionnaire for Functional Gastrointestinal Disorders in Adults(R4DQ)and compared to a sex-and agematched control group,to assess the burden of abdominal symptoms.Microsoft Excel and IBM SPSS v 25 were used for data analysis.RESULTS Fifty patients with acromegaly(24 male and 26 females;age range 23-64 years,mean 43)and 200 controls(96 male and 104 females;age range 18-84,mean 42.4)were recruited.92%(46 out of 50)of patients with acromegaly reported abdominal symptoms and 78%(39 out of 50)had at least one functional gastrointestinal disorder according to the Rome IV diagnostic criteria,compared to 16%of controls(OR>1,P<0.0001).The most commonly reported symptom was constipation(69%acromegaly vs 21%of controls OR>1,P<0.0001,95%CI:4.4–15.8).34 out of 50(68%)respondents met the criteria for functional constipation according to Rome IV.Upper gastrointestinal disorders were also more prevalent in the acromegaly group.There was no statistically significant difference in the prevalence of biliary and anorectal symptoms between the two groups.Patients in acromegaly group scored lower on the mean scores of the eight parameters of SF36 Quality of Life questionnaire(mean scores 60.04 vs 71.23,95%CI:-13.6829 to-8.6971,OR>1,P<0.001)as compared to the control group.CONCLUSION Upper and lower functional gastrointestinal tract disorders(defined by Rome IV diagnostic criteria)are significantly more prevalent in patients with acromegaly compared with healthy age and sex matched controls in our study.Functional constipation is the most commonly reported problem.Poorer quality of life may in part be attributable to the increased prevalence of abdominal symptoms.

Enduring association between irritable bowel syndrome and war trauma during the Nicaragua civil war period:A population-based study

BACKGROUND Psychosocial and physical trauma are known risk factors for irritable bowel syndrome(IBS),including in war veterans,whereas war exposure in civilians is unclear.Nicaragua experienced two wars,1970-1990:The Sandinistas Revolution(1970s)and The Contra War(1980s).Our aim was to investigate the role of exposure to war trauma in the subsequent development of IBS in the context of an established health surveillance system(11000 households).AIM To investigate in a civilian population the relationship between exposure to war trauma and events and the subsequent development of IBS in the context of an established public health and demographic surveillance system in western Nicaragua.METHODS We conducted a nested population-based,cross-sectional study focused on functional gastrointestinal disorders based on Rome II criteria.1617 adults were randomly selected.The Spanish Rome II Modular Questionnaire and Harvard Trauma Questionnaire were validated in Nicaragua.War exposure was assessed with 10 measures of direct and indirect war trauma and post-war effects.Multiple exposures were defined by≥3 measures.RESULTS The prevalence of IBS was 15.2%[Female(F)17.1%,Male(M)12.0%],war exposure 19.3%(F 9.3%,M 36.7%),and post-traumatic stress disorder(PTSD)5.6%(F 6.4%,M 4.3%).Significant associations with IBS in the civilian population were observed(adjusted by gender,age,socioeconomic status,education):physical and psychological abuse[adjusted odds ratio(aOR):2.25;95%confidence interval:1.1-4.5],witnessed execution(aOR:2.4;1.1-5.2),family member death(aOR:2.2;1.2-4.2),and multiple exposures(aOR:2.7;1.4-5.1).PTSD was independently associated with IBS(aOR:2.6;1.2-5.7).CONCLUSION An enduring association was observed in the Nicaragua civilian population between specific civil war-related events and subsequent IBS.Civilian populations in regions with extended armed conflict may warrant provider education and targeted interventions for patients.

Associations between irritable bowel syndrome and non-alcoholic fatty liver disease:A systematic review

BACKGROUND Irritable bowel syndrome(IBS)is associated with obesity and metabolic syndrome.IBS and non-alcoholic fatty liver disease(NAFLD)are highly prevalent entities worldwide and may share similar mechanisms including gut dysbiosis,impaired intestinal mucosal barrier and immune system activation.AIM To systematically review their association according to the Preferred Reporting Items for Systemic Review and Meta-analyses guidelines.METHODS PubMed,EMBASE and Cochrane Database of Systematic Reviews were searched for relevant papers.Manual searches were also performed.RESULTS Six studies were included.Both IBS and NAFLD subjects had significantly more metabolic risk factors like hypertension,obesity,dyslipidaemia and diabetes.Our review showed that 23.2%to 29.4%of NAFLD patients had IBS.IBS was significantly higher in NAFLD patients compared with patients without NAFLD(23.2%vs 12.5%,P<0.01).A higher proportion of IBS patients had NAFLD(65.8%to 74.0%).IBS patients were three times more likely to have NAFLD compared with non-IBS patients(P<0.001).Two studies showed a significant correlation between the severity of IBS and NAFLD.The proportion of NAFLD subjects with IBS increased with NAFLD severity.CONCLUSION Further prospective studies are warranted to evaluate the relationship and shared pathways between IBS and NAFLD,potentially leading to the development of future therapeutics.

Thinking and Strategy on the Diagnosis and Treatment of Functional Gastrointestinal Disorders with Integrative Medicine

The functional gastrointestinal disorders (FGIDs) are a group of diseases mainly manifested as gastrointestinal functional disorders,including 45 kinds of different diseases,such as functional dyspepsia(FD), irritable bowel syndrome (IBS),functional constipation

A Breakthrough Point in Integrative Medical Research:Challenge of Treating Overlapping Symptoms in Functional Gastrointestinal Disorders

Functional gastrointestinal disorders(FGIDs)are common disorders that are characterized by persistent and recurring gastrointestinal symptoms.Many patients with FGIDs have overlapping symptoms,which impaired the quality of life and ability to work of patients,and left a considerable impact on health-care systems and society.Chinese medicines(CMs)are commonly utilized by many patients with FGIDs.This article discusses the current status of diagnosis and treatment of FGIDs,the advantages and characteristics of CM treatment,and how integrated medicine can make a breakthrough in FGIDs diagnosis and treatment.

Childhood constipation:Current status,challenges,and future perspectives

Constipation in children is a major health issue around the world,with a global prevalence of 9.5%.They present to clinicians with a myriad of clinical signs.The Rome IV symptom-based criteria are used to diagnose functional constipation.Functional constipation is also a huge financial burden for healthcare system and has a detrimental impact on health-related quality of life of children.There are various risk factors identified globally,including centrally connected factors such as child abuse,emotional and behavioral issues,and psychological stress.Constipation is also precipitated by a low-fiber diet,physical inactivity,and an altered intestinal microbiome.The main pathophysiological mechanism is stool withholding,while altered rectal function,anal sphincter,pelvic floor,and colonic dysfunction also play important roles.Clinical evaluation is critical in making a diagnosis,and most investigations are only required in refractory patients.In the treatment of childhood constipation,both nonpharmacological(education and demystification,dietary changes,toilet training,behavioral interventions,biofeedback,and pelvic floor physiotherapy),and pharmacological(osmotic and stimulant laxatives and novel drugs like prucalopride and lubiprostone)interventions are used.For children with refractory constipation,transanal irrigation,botulinum toxin,neuromodulation,and surgical treatments are reserved.While frequent use of probiotics is still in the experimental stage,healthy dietary habits,living a healthy lifestyle and limiting exposure to stressful events,are all beneficial preventive measures.

Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea:Randomized controlled trial

BACKGROUND Irritable bowel syndrome(IBS)is a highly prevalent gastrointestinal disorder with poor response to treatment.IBS with predominant diarrhea(IBS-D)is accompanied by abdominal pain as well as high stool frequency and urgency.Purified clinoptilolite-tuff(PCT),which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®,has previously shown therapeutic potential in other indications based on its physical adsorption capacity.AIM To assess whether symptoms of IBS-D can be ameliorated by oral treatment with PCT.METHODS In this randomized,placebo-controlled,double-blind pilot study,30 patients with IBS-D diagnosis based on Rome IV criteria were enrolled.Following a 4-wk run-in phase,14 patients were randomized to receive a 12-wk treatment with G-PUR®(2 g three times daily),and 16 patients received placebo.The relief from IBS-D symptoms as measured by the proportion of responders according to the Subject’s Global Assessment(SGA)of Relief was assessed as the primary outcome.For the secondary outcomes,validated IBS-D associated symptom questionnaires,exploratory biomarkers and microbiome data were collected.RESULTS The proportions of SGA of Relief responders after 12 wk were comparable in both groups,namely 21%in the G-PUR®group and 25%in the placebo group.After 4 wk of treatment,36%of patients in the G-PUR®group vs 0%in the placebo group reported complete or considerable relief.An improvement in daily abdominal pain was noted in 94%vs 83%(P=0.0353),and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR®and placebo groups,respectively.Positive trends were observed for 50%of responders in the Bristol Stool Form Scale.Positive trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire score.Only 64%in the G-PUR®group compared to 86%in the placebo group required rescue medication intake during the study.Stool microbiome studies showed a minor increase in diversity in the G-PUR®group but not in the placebo group.No PCT-related serious adverse events were reported.CONCLUSION In this randomized,double-blind,placebo-controlled study,the PCT product,G-PUR®,demonstrated safety and clinical benefit towards some symptoms of IBS-D,representing a promising novel treatment option for these patients.