Yuri A. Saito

The epidemiology of irritable bowel syndrome in North America: A systematic review

OBJECTIVE:The aim of this study was to systematically review published literature about the prevalence, incidence, and natural history of irritable bowel syndrome (IBS) in North America.METHODS:A computer-assisted search of MEDLINE, EMBASE, and Current Contents/Science Edition databases was performed independently by two investigators. Study selection criteria included: 1) North American population-based sample of adults; 2) objective diagnostic criteria for IBS (i.e., Rome or Manning criteria); and 3) publication in full manuscript form in English. Eligible articles were reviewed in a duplicate and independent manner. Data extracted were converted into individual tables and presented in descriptive form.RESULTS:The prevalence of IBS in North America ranges from 3% to 20%, with most prevalence estimates ranging from 10% to 15%. The prevalences of diarrhea-predominant and constipation-predominant IBS are both approximately 5%. Published prevalence estimates by gender range from 2:1 female predominance to a ratio of 1:1. Constipation-predominant IBS is more common in female individuals. The prevalence of IBS varies minimally with age. No true population-based incidence studies or natural history studies were found. In one cohort surveyed on two occasions 1 yr apart, 9% of subjects who were free of IBS at baseline reported IBS at follow-up producing an onset rate of 67 per 1000 person-years. In all, 38% of patients meeting criteria for IBS did not meet IBS criteria at 1-yr follow-up.CONCLUSION:Approximately 30 million people in North America meet the diagnostic criteria for IBS. However, data about the natural history of IBS is quite sparse and renewed efforts should be focused at developing appropriately designed trials of the epidemiology of IBS.

Efficacy of Prebiotics, Probiotics, and Synbiotics in Irritable Bowel Syndrome and Chronic Idiopathic Constipation: Systematic Review and Meta-analysis

OBJECTIVES:Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC.METHODS:MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI.RESULTS:The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70–0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02–1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67–0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn.CONCLUSIONS:Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain.

American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15 % of the general population experiencing symptoms that would satisfy a defi nition of IBS ( 1,2 ). In a systematic review on the global prevalence of IBS, Lovell and Ford ( 1 ) documented a pooled prevalence of 11 % with all regions of the world suff ering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and / or raising families, the socioeconomic impact of IBS is considerable. Th ese indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford ( 3 ) reported a pooled prevalence of 14 % , and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status ( 3 ). Chronic constipation has also been linked to impaired quality of life ( 4 ), most notably among the elderly ( 5 ). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical defi nitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defi ned on the basis of the presence of:

A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome

Abstract OBJECTIVE: The aim of this study was to estimate the prevalence of irritable bowel syndrome using different standard definitions (Rome and Manning criteria) and to determine the degree of agreement between these definitions. METHODS: A population-based, cross-sectional survey study was conducted by mailing a valid, reliable questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN, aged 30–69 yr. The threshold for a positive diagnosis of irritable bowel was varied from two to four of the six Manning criteria and from two to three of the five defecation disorders in the Rome criteria. Unadjusted as well as age- and gender-adjusted prevalence rates were calculated for each of the five definitions of IBS. Percent agreement and κ statistics were calculated to assess agreement between the definitions. RESULTS: Questionnaires were returned by 643 of 892 eligible subjects (72% response rate). The age- and gender-adjusted prevalence of IBS varied from 20.4% using a threshold of two symptoms in the Manning criteria to 8.5% using a threshold of three defecation disorders in the Rome criteria. The percent agreement for each comparison of Manning and Rome definitions was always >90%. The κ values ranged from 0.55 to 0.78, with the best agreement occurring between a threshold of three symptoms of Manning and two defecation disorders in Rome. CONCLUSIONS: The prevalence of IBS varied substantially depending on the specific definition of IBS used. The range of prevalence estimates in Olmsted County was similar to other published figures when IBS definition was accounted for. These findings are useful in interpreting epidemiological and clinical studies of IBS.

Effect of Antidepressants and Psychological Therapies, Including Hypnotherapy, in Irritable Bowel Syndrome: Systematic Review and Meta-Analysis

OBJECTIVES:Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate.METHODS:We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or “usual management,” were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI).RESULTS:The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or “usual management,” sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58–0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61–0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial.CONCLUSIONS:Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

Diet and functional gastrointestinal disorders: a population based case-control study

BACKGROUND:Diet has been implicated to play a role in functional gastrointestinal disorders (FGID) in clinic-based studies. No population-based data comparing food and nutrient consumption between individuals with FGID and without gastrointestinal symptoms are available.OBJECTIVES:The purpose of this study was to compare the dietary consumption of specific food items and nutrients between individuals with FGID and without symptoms in a population-based sample.METHODS:A validated self-report Bowel Disease Questionnaire was mailed to an age- and gender-stratified random sample of participants aged 20–50 yr from Olmsted County, Minnesota. All patients who reported either FGID symptoms (irritable bowel or dyspepsia) or no gastrointestinal symptoms were invited to undergo a blinded physician interview and physical exam and to complete a validated Harvard Food Frequency Questionnaire. Wilcoxon rank sum tests and logistic regression were used for statistical analysis.RESULTS:In total, 222 of the 260 eligible (85%) subjects participated and 218 provided diet data: 99 were FGID cases and 119 were healthy controls. Cases and controls consumed similar number of servings per week of wheat-containing foods, lactose-containing foods, caffeinated drinks, and fructose-sweetened beverages. Cases were slightly more likely to consume ≥7 servings per week of norepinephrine- and epinephrine-containing foods (57% vs 45%, p = 0.10), but not serotonin- or tryptophan-containing foods. No differences were observed for amount of intake of calories, fiber, protein, iron, calcium, niacin, and vitamins C, D, E, niacin, B1, B2, B6, and B12. Cases reported consuming more fat (median, 33% vs 31%) and less carbohydrates (median, 49% vs 52%) than controls.CONCLUSIONS:No differences were seen in the consumption of frequently suspected “culprit” foods between community residents with and without FGID symptoms. While symptoms may be due to food sensitivity rather than altered diet composition, the role of fat and perhaps norepinephrine and epinephrine in foods in gut symptoms needs to be studied further.

Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy

The SCN5A-encoded Na(v)1.5 Na(+) channel is expressed in interstitial cells of Cajal and smooth muscle in the circular layer of the human intestine. Patients with mutations in SCN5A are more likely to report gastrointestinal symptoms, especially abdominal pain. Twin and family studies of irritable bowel syndrome (IBS) suggest a genetic basis for IBS, but no genes have been identified to date. Therefore, our aims were to evaluate SCN5A as a candidate gene involved in the pathogenesis of IBS and to determine physiological consequences of identified mutations. Mutational analysis was performed on genomic DNA obtained from 49 subjects diagnosed with IBS who reported at least moderately severe abdominal pain. One patient hosted a loss-of-function missense mutation, G298S, that was not observed in >3,000 reference alleles derived from 1,500 healthy control subjects. Na(+) currents were recorded from the four common human SCN5A transcripts in transfected HEK-293 cells. Comparing Na(v)1.5 with G298S-SCN5A versus wild type in HEK cells, Na(+) current density was significantly less by 49-77%, and channel activation time was delayed in backgrounds that also contained the common H558R polymorphism. Single-channel measurements showed no change in Na(v)1.5 conductance. Mechanosensitivity was reduced in the H558/Q1077del transcript but not in the other three backgrounds. In conclusion, the G298S-SCN5A missense mutation caused a marked reduction of whole cell Na(+) current and loss of function of Na(v)1.5, suggesting SCN5A as a candidate gene in the pathophysiology of IBS.

The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis.

OBJECTIVES:Fiber has been used for many years to treat irritable bowel syndrome (IBS). This approach had fallen out of favor until a recent resurgence, which was based on new randomized controlled trial (RCT) data that suggested it might be effective. We have previously conducted a systematic review of fiber in IBS, but new RCT data for fiber therapy necessitate a new analysis; thus, we have conducted a systematic review of this intervention.METHODS:MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched up to December 2013. Trials recruiting adults with IBS, which compared fiber supplements with placebo, control therapy, or “usual management”, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy as well as number needed to treat (NNT) with a 95% confidence interval (CI).RESULTS:We identified 14 RCTs involving 906 patients that had evaluated fiber in IBS. There was a significant benefit of fiber in IBS (RR=0.86; 95% CI 0.80–0.94 with an NNT=10; 95% CI=6–33). There was no significant heterogeneity between results (I2=0%, Cochran Q=13.85 (d.f.=14), P=0.46). The benefit was only seen in RCTs on soluble fiber (RR=0.83; 95% CI 0.73–0.94 with an NNT=7; 95% CI 4–25) with no effect seen with bran (RR=0.90; 95% CI 0.79–1.03).CONCLUSIONS:Soluble fiber is effective in treating IBS. Bran did not appear to be of benefit, although we did not uncover any evidence of harm from this intervention, as others have speculated from uncontrolled data.

Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography.

Background  Improvement in subjective symptoms has been reported in functional dyspepsia (FD) patients administered with acotiamide. Improvement was confirmed in meal‐related symptoms, such as postprandial fullness, upper abdominal bloating, and early satiety. We examined the mechanism underlying the effects of acotiamide on gastric accommodation reflex (GAR) and gastroduodenal motility in FD patients.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

BACKGROUND & AIMS Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.