Irritable Bowel Syndrome Diarrhea Research Articles

Clinical effect of abdominal acupuncture for diarrhea irritable bowel syndrome

To compare the efficacy differences between abdominal acupuncture and western medication for diarrhea irritable bowel syndrome (IBS-D). Sixty-one patients with IBS-D were randomly assigned into an acupuncture group (30 cases after 1 dropping) and a western medication group (28 cases after 2 dropping). Acupuncture was used at Yinqiguiyuan points [Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanyuan (CV 4)], Fusiguan points [bilateral Huaroumen (ST 24), Wailing (ST 26)], Tiaopiqi point [bilateral Daheng (SP 15)], once every other day, 3 times a week. Pinaverium bromide tablet was used orally in the western medication group, 50 mg a time, 3 times a day. All the treatment was given for 4 weeks in the two groups. IBS symptom severity score (IBS-SSS) and clinical symptom scores for abdominal pain and distension, diarrhea, poor stool output, defecation urgency and stool abnormality were observed before and after the treatment as well as 3 months after treatment. Adverse reactions were recorded and the effects were evaluated. ①After treatment and at follow-up, the IBS-SSS scores of the two groups were lower than those before treatment (all P<0.01). Compared with the western medication group, the scores and the improvements between the two time points and before treatment were better in the acupuncture group (P<0.05, P<0.01). ②The symptom scores in the two groups after treatment were lower than those before treatment including abdominal pain, abdominal distension, diarrhea, poor stool output, defecation urgency and stool abnormality (P<0.05, P<0.01), and the scores of abdominal pain, abdominal distension, diarrhea, poor stool output and stool abnormality in the acupuncture group were lower than those in the western medication group (P<0.05, P<0.01). ③The total effective rate and the cured and remarkable effective rate of the acupuncture group were higher than those of the western medication group [(86.7% (26/30) vs 64.3% (18/28), P<0.05; 70.0% (21/30) vs 35.7% (10/28), P<0.01)], and the therapeutic efficacy of the acupuncture group was better than that of the western medication group (P<0.05). There was no adverse reaction. Abdominal acupuncture is more effective for IBS-D than western medication and can relieve abdominal pain, abdominal distension, diarrhea, poor stool output, stool abnormality, with long-term effect.

Micronutrient Intake Changes With the Low FODMAP and mNICE Diets

Introduction: The role of the low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet has gained increasing acceptance for the treatment of irritable bowel syndrome (IBS) but potential safety concerns have been raised regarding nutritional adequacy. Changes in micronutrient intake with a low FODMAP diet have not been previously investigated. Daily micronutrient intake after 4 weeks of a low FODMAP diet or a modified NICE (mNICE) diet was compared to baseline. Methods: A post-hoc analysis of a single-center, randomized-controlled trial of adult patients with IBS-Diarrhea (IBS-D) was utilized which compared the efficacy of a low FODMAP and the mNICE diets on IBS symptoms over a 4-week period. The Nutrition Data System for Research (NDSR) computer program was used to analyze 3-day food diaries at baseline and at 4 weeks. Results: Data from 78 patients who completed the study were included. 41 patients were randomized to the low FODMAP diet and 37 patients were randomized to the mNICE diet. The average BMI in the low FODMAP group was 27.7 ± 6.5 compared to an average BMI of 31.4 ± 7.9 in the mNICE group (p=0.003). Both diets resulted in fewer daily kilocalories and number of daily meals consumed (Table 1). Among the patients on the low FODMAP diet, a statistically significant decrease from baseline in the daily intake retinol, thiamin, riboflavin, calcium, and trans-fatty acids was observed. There was a statistically significant increase from baseline in the intake of vitamin B6. In the mNICE group, there was a statistically significant decrease in the daily intake of polyunsaturated fatty acids only. The remaining micronutrient differences compared to baseline were not statistically significant.Table: No Caption availableConclusion: During a 4-week dietary intervention, the average daily intake of most micronutrients remained stable and within recommended dietary allowances. A low FODMAP diet was associated with a significantly lower daily intake of retinol, thiamin, riboflavin, calcium, trans-fatty acids, while the daily intake of vitamin B6 was increased. The mNICE diet was associated only with lower daily intake of polyunsaturated fatty acids. While statistically significant, the clinical significance of these findings are unclear and suggest that for a short-term elimination diet, the low FODMAP diet is not associated with major micronutrient inadequacies. These findings reinforce the importance of diversifying a patient's diet through reintroduction of foods containing FODMAPs.

Association between self-reported vegetarian diet and the irritable bowel syndrome in the French NutriNet cohort.

BackgroundThere is growing interest in using diet counselling in the management of patients with irritable bowel syndrome (IBS). Among new emerging diets, vegetarian diets (VD) seem to be experiencing an important popularity, partly because of their alleged health benefits. A recent study performed among a rural Indian population showed that predominant VD could be associated with IBS.ObjectiveThis cross-sectional study aimed at assessing the association between the VD and IBS, among a large French cohort, the NutriNet-santé study.MethodsSubjects participating in the NutriNet-Santé cohort study completed a questionnaire based on Rome III criteria (N = 41,682). Anthropometrics, socio-demographical and lifestyle data, including VD, were collected prior to the completion of Rome III questionnaire via self-administered questionnaires. Association between VD and IBS and its subtypes was investigated through multivariate logistic regression.ResultsThe included subjects were mainly women (78.0%) and the mean age was 49.8±14.3 years. Among these individuals, 2,264 (5.4%) presented an IBS, and 805 (1.9%) reported a VD. Overall, VD was not associated with IBS or subtypes. A stable VD (i.e. self-declared at least three times) was associated with IBS (aOR 2.60 95%CI [1.37–4.91]), IBS mixed (aOR 2.97 95%CI [1.20–7.36]) and IBS diarrhoea (aOR 2.77 95%CI [1.01–7.59]).ConclusionsThis study suggests that a long term VD could be associated with IBS. Nevertheless, further studies are needed to confirm these results, and investigate the multiple aspects of the vegetarian diet, possibly related to the IBS.

Exam 2: Colonic Transit and Bile Acid Synthesis or Excretion in Patients With Irritable Bowel Syndrome–Diarrhea Without Bile Acid Malabsorption

Exam 2: Colonic Transit and Bile Acid Synthesis or Excretion in Patients With Irritable Bowel Syndrome–Diarrhea Without Bile Acid Malabsorption

Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome.

Serum‐derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open‐label study in 15 patients with irritable bowel syndrome‐diarrhea (IBS‐D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability (13C‐mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF‐19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa. Statistical analysis (paired tests, baseline vs. treatment) was based on intention to treat (ITT) principles. One of 15 Caucasian patients (13F, 2M, age 40.3 ± 2.3y, BMI 34.3 ± 3.0 kg/m2) withdrew without completing studies. There were improvements in stools/day (decrease, P < 0.001), ease of passage (P = 0.035), and evacuation (P = 0.004) with SBI therapy. Worst pain severity was numerically reduced in last 2 weeks' treatment (P = 0.078). Duodenal mucosal mRNA expression; serum C4, FGF‐19, and KT ratio; small bowel or colon permeability; and stool microbiome were not significantly different after SBI therapy, compared to baseline. In duodenal brushings, there was considerable microbiota structure difference (β diversity analysis P = 0.072, UniFrac) and, on taxonomic analysis, increased abundance of Proteobacteria Burkholderiales, Firmicutes Catonella, and unclassified genus organisms with SBI therapy. Thus, SBI therapy for 8 weeks in IBS‐D patients is associated with improved bowel function; the mechanism of benefit is unclear, though there were microbiota structure differences in duodenal brushings. Further studies in patients with low‐grade inflammation and intestinal barrier dysfunction at baseline are indicated.

Acupuncture with regulating mind and spleen for diarrhea irritable bowel syndrome and sleep quality:a randomized controlled trial

To compare the effects between acupuncture with regulating mind and spleen and wes-tern medication for diarrhea irritable bowel syndrome (IBS-D). Eighty-one patients were randomly at the ratio of 2 to 1 assigned into an acupuncture group (54 cases) and a western medication group (27 cases). Acupuncture with regulating mind and spleen was applied in the acupuncture group for 6 weeks at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37), Sanyinjiao (SP 6), and Taichong (LR 3), once every other day, 3 times a week. Pinaverium bromide tablet was used orally in the western medication group for 6 weeks, 50 mg a time, 3 times a day. IBS symptom severity score (IBS-SSS) were observed before and after 1-week, 6-week treatment. Pittsburgh sleep quality index (PSQI) was applied before and after 6-week treatment. Also, clinical efficacy was evaluated in the two groups. Three patients dropped out in the acupuncture group, and 1 in the western medication group. Except abdominal distension score after 1-week treatment in the western medication group, single scores and total scores of IBS-SSS apparently reduced in the two groups after 1-week and 6-week treatment (P<0.01, P<0.05). After 1-week treatment, the abdominal pain score of the acupuncture group was obviously lower than that of the western medication group (P<0.05). After 6-week treatment, with abdominal pain relief advantage, other results including the number of pain days, defecation satisfaction,life disturbance degree and total score of the acupuncture group were obviously lower than those of the wes-tern medication group (P<0.01,P<0.05). After 6-week treatment, the PSQI score and its change before and after treatment in the acupuncture group were superior to those in the western medication group (both P<0.05). The relief rate and relief plus obvious effective rate in the acupuncture group were higher than those in the western medication group[51.0% (26/51) vs 19.2% (5/26), P<0.01; 64.7% (33/51) vs 34.6% (9/26), P<0.05]. Acupuncture with regulating mind and spleen for diarrhea irritable bowel syndrome can more effectively relieve abdominal pain than pinaverium bromide tablet at the early stage. Its total effect and single effects are better at the later stage on abdominal pain, seizure frequency, defecation satisfaction, life disturbance, and sleep quality.

Review of Rifaximin: Latest Treatment Frontier for Irritable Bowel Syndrome Mechanism of Action and Clinical Profile

Background:Irritable bowel syndrome is classified as a functional gastrointestinal disorder with the primary symptom of abdominal pain in conjunction with bloating and bowel movement disorder. It affects up to 15% of the world’s population. Among its subtypes, the most common is diarrhoea predominant. However, the current treatment options for diarrhoea-predominant irritable bowel syndrome have had not very promising results; most, such as antispasmodics, only provide partial symptomatic relief. Treatment with antidepressants and alosetron (a 5HT3 antagonist) has shown the most promise to date. The latest drug to be approved for the treatment of irritable bowel syndrome-diarrhoea is rifaximin, which was approved in May 2015. It is a minimally absorbed antibiotic that is used to change the gut microbiota. Small intestinal bacterial overgrowth is one of the causes suggested for irritable bowel syndrome, particularly for the diarrhoea-predominant type. There are various methods for detecting bacterial overgrowth, the simplest of which is breath tests. Rifaximin has been shown to be of benefit to these patients.Purpose:The purpose of the study is to discuss the potential mechanism of action of rifaximin, a minimally absorbed antibiotic. In addition, we evaluate the various clinical trials undertaken to study the efficacy and safety profile of rifaximin.

Colonic Transit and Bile Acid Synthesis or Excretion in PatientsWith Irritable Bowel Syndrome-Diarrhea Without BileAcid Malabsorption.

Bile acids (BAs) are passively absorbed to a different extent along the mammalian colon, so that levels are lower in the feces than in proximal colon. Our aim was to explore associations among total, primary, and secretory BA in stool and colonic transit in patients with irritable bowel syndrome-diarrhea (IBS-D) without overt BA malabsorption (BAM). In a cross-sectional observational study of 116 patients with IBS-D recruited from local communities in Minnesota, we measured total and individual main fecal BA excretion, fecal fat and fecal weight over 48 hours, fasting serum levels of C4 (surrogate for BA synthesis), and overall colonic transit by scintigraphy (geometric center at 24 hours and 48 hours). Patients without overt BAM were assigned to groups based on total fecal BA level below 2337 μmol/48 hours (n= 86) or serum levels of C4 below 47.1 ng/mL (n= 91). We used Spearman correlations to test study hypotheses with correction for 14 correlations tested (P < .0036). Data from 30 healthy volunteers were used as control subjects. Patients with IBS-D who had increased or normal total BA excretion in stool or BA synthesis had higher stool proportions of primary BAs (especially chenodeoxycholate), compared with healthy control subjects. In patients with IBS-D without overt BAM (normal 48-hour total fecal BA or serum C4), there were significant positive correlations between total fecal BA, fecal primary and secretory BA, fecal weight, and increased geometric center at 24 and 48 hours (P<.0036). Normal and slightly increased levels of total fecal BA have greatest effects on colonic transit at 48 hours. In the absence of overt BAM, the total, primary, and secretory BAs in stool contribute to the acceleration of colonic transit and fecal weight in the diarrhea of patients with IBS-D.

Eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome

ABSTRACTIntroduction: Irritable bowel syndrome (IBS) treatment is challenging physicians because of its multifactorial physiopathology. In particular, abdominal pain and diarrhea management lack one unique effective pharmacological remedy. Opioid receptors, present in the central nervous system (CNS) and the enteric nervous system (ENS), are involved in visceral sensitivity and gastrointestinal motility control. To date only a few opioid receptor modulators are currently in use for the treatment of IBS but with dosage limitations due to the early development of severe constipation.Areas covered: In this drug evaluation manuscript we review the irritable bowel syndrome therapeutic needs and chemistry, pharmacokinetics and -dynamics, clinical study results with the new opioid receptor ligand eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D).Expert opinion: Eluxadoline shows a peculiar pharmacological profile with μ-opioid agonism and δ-opioid antagonism actions. Its efficacy over placebo for the treatment of abdominal pain and diarrhea in IBS-D has been demonstrated in short- and long-term clinical studies in humans. Its safety has been evaluated in the same studies. Interestingly, eluxadoline showed a low rate of constipation development in IBS patients in comparison with known effects of other opioid receptor modulators. Patients with a history of acute pancreatitis should not be treated with eluxadoline.

Tu1809 Small Intestinal Mucosal Expression of Candidate Pathobiological Mechanisms in IBS-Diarrhea (IBS-D) and Healthy Controls

Tu1809 Small Intestinal Mucosal Expression of Candidate Pathobiological Mechanisms in IBS-Diarrhea (IBS-D) and Healthy Controls

Frequency of subtypes of irritable bowel syndrome in positive and negative subtypes of schizophrenia

ObjectiveThe aim of the study was to determine the frequency of subtypes of irritable bowel syndrome in positive and negative subtypes of schizophrenia.MethodsSixty-two drug naïve hospitalized patients between 18 and 65 years (mean age: 33.6) with first episode of schizophrenia based on DSM IV-TR and 69 control subjects matched for age and sex completed this study. A semi-structured clinical interview was used to assess both groups. Clinical data were obtained and basic lab investigations and ultrasonography of abdomen were done in all subjects to exclude any related abdominal pathology. Axis-I disorders of DSM IV-TR were excluded in control subjects. Positive and Negative Syndrome Scale (PANSS) and Rome III Urdu language version scale (cross-validation obtained) for irritable bowel syndrome (IBS) were administered to assess the severity of positive and negative symptoms of schizophrenia and subtypes of irritable bowel syndrome, IBS constipation (IBS-C), IBS Diarrhoea (IBS-D) and IBS Mix (IBS-M) in case and control groups respectively.ResultsForty-seven patients (75.8%) and 15 patients (24.2%) had positive and negative schizophrenia respectively. Patients with positive and negative schizophrenia had higher rate of IBS-C 6.5% (n = 4), IBS-D 8.1% (n = 5), IBS-M 12.9% (n = 8), non-IBS 72.6% (n = 45) versus healthy subjects IBS-C 1.4% (n = 1), IBS-D 2.9% (n = 2), IBS-M 2.9% (n = 2), and non-IBS 92.8% (n = 64), OR = 4.8; 95% CI.ConclusionIrritable bowel syndrome is more frequent in patients with schizophrenia than in general population. This functional gastrointestinal disorder associated with psychotic symptoms requires attention and management while managing patients with subtypes of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Prevalence of microscopic colitis in Upper Egypt among patients with chronic diarrhea and patients with irritable bowel syndrome

Aim The aim of this study was to evaluate the prevalence of microscopic colitis (MC) in patients with chronic watery diarrhea and irritable bowel syndrome–diarrhea (IBS-D) predominant. Patients and methods We studied 61 patients with chronic nonbloody diarrhea and normal endoscopic findings prospectively for 2 years' duration; 37 patients had chronic watery diarrhea for investigation and 24 had IBS-D predominant. Results Our results showed that 18 (29.5%) patients had MC, 10 (16.4%) patients had collagenous colitis, and eight (13.1%) had lymphocytic colitis. Four (16.7%) patients out of the 24 patients with IBS-D predominant had MC. Abdominal pain, nocturnal diarrhea, and weight loss are the most common clinical presentation in MC. Conclusion MC is not uncommon in Upper Egypt patients with chronic watery diarrhea and normal colonoscopic findings. Biopsy of normal colonic mucosa in patients with chronic watery diarrhea is emphasized to reach to definite diagnosis of MC.

Exam 1: Intestinal Secretory Mechanisms in Irritable Bowel Syndrome–Diarrhea

Exam 1: Intestinal Secretory Mechanisms in Irritable Bowel Syndrome–Diarrhea

248 Candidate Genes, Mucosal mRNA and Protein Expression, Colon Transit and Bile Acid Excretion in Irritable Bowel Syndrome-Diarrhea

248 Candidate Genes, Mucosal mRNA and Protein Expression, Colon Transit and Bile Acid Excretion in Irritable Bowel Syndrome-Diarrhea

Irritable bowel syndrome subtypes: Clinical and psychological features, body mass index and comorbidities.

Irritable bowel syndrome (IBS) is classified into subtypes according to bowel habit. To investigate whether there are differences in clinical features, comorbidities, anxiety, depression and body mass index (BMI) among IBS subtypes. The study group included 113 consecutive patients (mean age: 48 ± 11 years; females: 94) with the diagnosis of IBS. All of them answered a structured questionnaire for demographic and clinical data and underwent upper endoscopy. Anxiety and depression were assessed by the Hospital Anxiety and Depression scale (HAD). The distribution of subtypes was: IBS-diarrhea (IBS-D), 46%; IBS-constipation (IBS-C), 32%, and mixed IBS (IBS-M), 22%. IBS overlap with gastroesophageal reflux disease (GERD), functional dyspepsia, chronic headache and fibromyalgia occurred in 65.5%, 48.7%, 40.7% and 22.1% of patients, respectively. Anxiety and/or depression were found in 81.5%. Comparisons among subgroups showed that bloating was significantly associated with IBS-M compared to IBS-D (odds ratio-OR-5.6). Straining was more likely to be reported by IBS-M (OR 15.3) and IBS-C (OR 12.0) compared to IBS-D patients, while urgency was associated with both IBS-M (OR 19.7) and IBS-D (OR 14.2) compared to IBS-C. In addition, IBS-M patients were more likely to present GERD than IBS-D (OR 6.7) and higher scores for anxiety than IBS-C patients (OR 1.2). BMI values did not differ between IBS-D and IBS-C. IBS-M is characterized by symptoms frequently reported by both IBS-C (straining) and IBS-D (urgency), higher levels of anxiety, and high prevalence of comorbidities. These features should be considered in the clinical management of this subgroup.

Patients Sith Diarrhea-Predominant Irritable Bowel Syndrome Have Lower Disease-Specific Quality of Life Than Constipation-Predominant Irritable Bowel Syndrome

Introduction: Irritable bowel syndrome (IBS) specific quality of life (IBS-QOL) questionnaire is the most extensively-validated health-related QOL-specific instrument for IBS. There is a paucity of data on the effect of IBS-subtype on the IBS-QOL. We carried out a prospective, cross-sectional study of IBS patients visiting our functional gastroenterology disorder clinic at a quaternary care center to determine the effect of IBS subtype on the overall IBS-QOL and its various subscales from 2011 to 2013. Methods: IBS and IBS subtype were diagnosed using a Rome-III questionnaire and the IBS-QOL was administered to all patients once they were diagnosed with IBS. The overall IBS and the individual subscale scores were calculated as per the IBS-QOL scoring manual and were scored on a range of 0-100 with higher score suggestive of better QOL. Similar scores on a range of 1-100 were reported for all the 8 subscales - body image, food avoidance, interference with activity, relationship, social reaction, sexual, health worry, and dysphoria. Results: Of 474 patients screened over the last 2 years, 215 met Rome III criteria for IBS. IBS-mixed type (IBS-M) was the most common subtype (109 patients, 50.7%) followed by IBS-diarrhea (IBS-D) (49 patients, 22.8%), IBS-constipation (IBS-C) (46 patients, 21.4%), and IBS-unspecified (IBS-U) (11 patients, 5.1%). Patients with IBS-D had lowest IBS-QOL (59.1; 95% CI, 52.7-65.5) followed by IBS-M (61.9; 95% CI, 56.8-67), IBS-C (70.9; 95% CI, 63-78.8) and IBS-U (74.8; 95% CI, 58.4-91.3). Overall IBS-QOL of patients with IBS-D was significantly lower than patients with IBS-C (p=0.01) and IBS-U (p=0.04). Patients with IBS-D scored significantly lower than IBS-C on following domains - food avoidance (37.8; 95% CI, 28.4-47.1 vs. 54.5; 95% CI, 43.1-65.8, p=0.02), interference with activity (58.5; 95% CI, 51.4-65.6 vs. 79.5; 95% CI, 72.4-86.6, p<0.001), and relationship (73.1; 95% CI, 66.6-79.6 vs. 82.9; 95% CI, 76.5-89.4, p=0.03). Conclusion: Patients with IBS-D have lower disease-specific QOL than IBS-C patients. Clinicians should consider paying special attention to food avoidance, effects on daily activities and problems with relationships in IBS-D patients as these domains significantly affect QOL. Interventions targeted towards these QOL domains could provide the greatest impact this subset of IBS patients. Disclosure - Dr. Kuo: Consultant Furiex, Biogen, Theravance, Genova, Given Imaging, Research Support: GSK, Given, Furiex.

Validating biomarkers of treatable mechanisms in irritable bowel syndrome.

A valid biomarker is 'an indicator of normal biologic or pathogenic processes, or pharmacological responses to a therapeutic intervention'. There is no validated biomarker for irritable bowel syndrome (IBS). The aim of the study was to assess ability of three quantitative traits to identify treatable processes to discriminate between IBS-diarrhea (IBS-D) patients, IBS-constipation (IBS-C) patients and healthy volunteers (HV). In 30 HV, 30 IBS-C patients and 64 IBS-D patients, we characterized bowel symptoms and quantitated pathophysiological mechanisms: bile acid (BA) synthesis (serum C4 and FGF19), fecal BA and fat, colonic transit (CT), and intestinal permeability (IP). We used multiple logistic regression and receiver-operating characteristic (ROCAUC ) to appraise three factors (fecal BA, CT, and IP) individually and in combination to identify discriminant targets for treatment in IBS. There were significant associations between the three subgroups and symptoms reflecting bowel function and the quantitative traits. There were significant associations between fecal BA and CT at 48 h (r = 0.43; p < 0.001) and between fecal BA and IP (r = 0.23; p = 0.015). Individually, fecal BA and CT48 (but not IP) were significant independent predictors for distinguishing HV from IBS. In combination, they discriminated HV from IBS-D patients (ROCAUC 0.70), HV from IBS-C patients (ROCAUC 0.73), and IBS-C patients from IBS-D patients (ROCAUC 0.86). Colonic transit and fecal BA excretion together discriminate between healthy volunteers and IBS-C patients or IBS-D patients, or between the IBS subgroups with 75-90% specificity at 60% sensitivity. Colonic transit and fecal BA individually and together constitute useful biomarkers to identify treatable mechanisms in IBS and to differentiate subgroups of IBS.

Effect of Increased Bile Acid Synthesis or Fecal Excretion in Irritable Bowel Syndrome-Diarrhea

Approximately 25% of patients with irritable bowel syndrome-diarrhea (IBS-D) have increased total fecal bile acids (BA) and serum C4 (surrogate for BA synthesis). BA synthesis-related genes (KLB and FGFR4) are associated with colonic transit (CT) in IBS-D. Our aims were: (i) to compare phenotype and pathophysiology in IBS-D patients with increased or normal fecal excretion or synthesis of BA; and (ii) to explore association of variations in two candidate bile-acid synthesis genes (KLB and FGFR4) in these two subgroups of IBS-D. A total of 64 IBS-D patients underwent on one occasion: fasting serum C4 and FGF19, total fecal fat and BA excretion, CT, intestinal and colonic permeability, and candidate genotyping (rs17618244 (KLB), rs351855 (FGFR4)). Colonic sensation and tone were measured in 47 of the IBS-D patients. IBS-D subgroups were identified by fecal BA >2,337 mM per 48 h or by serum C4 >47.1 ng/ml. IBS-D patients with fecal BA >2,337 mM per 48 h (19/54) had significantly greater body mass index, fecal fat, percent chenodeoxycholic acid (CDCA) in feces, and intestinal permeability, and borderline increased CT (P=0.13). Those IBS-D patients with serum C4 >47.1 ng/ml (13/54) had increased total fecal BA excretion and borderline increased colonic permeability. Variants in genes involved in feedback regulation of BA synthesis (KLB, P=0.06 and FGFR4, P=0.09) were potentially associated with the subgroup with elevated serum C4. IBS-D with increased BA excretion or synthesis is associated with significant pathophysiological changes relative to patients with normal BA profile. BA diarrhea is identified more effectively with total fecal BA than with serum C4.

Intestinal Secretory Mechanisms in Irritable Bowel Syndrome–Diarrhea

Although diarrhea is the predominant bowel dysfunction in as many as one-third of patients with irritable bowel syndrome (IBS), it is unclear whether there is a specific disorder of intestinal fluid or electrolyte secretion in IBS. Diarrhea is generally considered a result of accelerated colonic transit in patients with IBS. Although a primary secretory diathesis has not been well-documented in patients with IBS with diarrhea (IBS-D), several mechanisms that could potentially contribute to intestinal secretion have been reported. Some of these mechanisms also influence motor and secretory dysfunctions that contribute to the pathophysiology of IBS-D. We review the evidence supporting secretion in IBS-D caused by peptides and amines produced by enteroendocrine cells or submucosal neurons, enterocyte secretory processes, and intraluminal factors (bile acids and short-chain fatty acids). Understanding these mechanisms and developing clinical methods for their identification could improve management of patients with IBS-D.

Clinical expression of lymphocytic duodenosis in “mild enteropathy” celiac disease and in functional gastrointestinal syndromes

Objective. Abnormally high number of duodenal intraepithelial lymphocytes is frequently found in many conditions including mild enteropathy celiac disease (CD) and functional gastrointestinal syndromes, but is unclear whether lymphocytosis affects the clinical phenotype particularly in functional syndromes. Materials and methods. We compared clinical characteristics of celiac patients with lymphocytic duodenosis and normal villous structure with those of patients with functional gastrointestinal syndromes with and without lymphocytic duodenosis. We retrospectively identified 3 cohorts among patients referred for suspected CD: (1) “CoelD”, 135 patients (age 36 ± 14 years) with mild enteropathy CD; (2) “LymD”, 245 patients (38 ± 12 years) with functional gastrointestinal syndromes and lymphocytic duodenosis; and (3) “NorD”, 147 patients (37 ± 15 years) with functional syndromes and normal duodenal histology. Results. Prevalence of gastrointestinal symptoms was similar in the three cohorts, but prevalence of extra-intestinal manifestations (42% vs. 27% vs. 18%, p < 0.003) and of associated diseases (35% vs. 15% vs. 14%, p < 0.0001) was higher in “CoelD” than in “LymD” and “NorD”, respectively. Prevalence of Helicobacter pylori infection was similar in the three cohorts. The proportion of patients with final diagnosis of irritable bowel syndrome-diarrhea (38% vs. 37%), dyspepsia (31% vs. 27%), functional pain (14% vs. 19%), and functional diarrhoea (14% vs. 11%) was virtually the same in the cohorts with (LymD) and without (NorD) lymphocytic duodenosis. Conclusions. Lymphocytic duodenosis has different clinical presentation in patients with mild enteropathy CD than those with functional gastrointestinal syndromes, and is not specific for any particular functional syndrome.