Susanna Walter

A Population-based Study on Bowel Habits in a Swedish Community: Prevalence of Faecal Incontinence and Constipation

Background: The self-reported bowel habits and the prevalence of faecal incontinence and constipation in men and women between the ages of 31 and 76 are assessed. Methods: A postal questionnaire was sent to a random sample ( n = 2000) of the total population of persons between the ages of 31 and 76 living in the County of Östergötland, Sweden. Results: The response rate was 80.5%. Overall, 67.8% reported one bowel movement per day and 4.4% had more than 21 or less than 3 bowel movements per week. This means that 95.6% had between 3 bowel movements a day to 3 bowel movements a week. Among women, 4.3%, and among men, 1.7%, reported less than 3 bowel movements per week. Women and men used the same terms to describe the definition of constipation. Women had a significantly higher self-reported prevalence of constipation than men ( P < 0.0001). About 20% of all women considered themselves constipated. The use of laxatives increased with age and 22% and 10% of elderly women and men, respectively, used laxatives including bulking agents for at least every fourth toilet procedure. About 10% reported leakage of faeces more often than once a month in the case of loose stools. With solid faeces, the rate of leakage was 1.4% and 0.4% for women and men, respectively. Soiling of underclothes more than once a month occurred in 21% of men and in 14.5% of women ( P = 0.006) and involuntary daily leakage of gas in 5.9% of men and 4.9% of women (n.s.). Conclusions: Constipation and faecal incontinence are common problems in a general Swedish population.

Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome.

BACKGROUND & AIMS Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences. METHODS We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest. RESULTS The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls. CONCLUSIONS Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.

Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts

Objective IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. Design We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. Results One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10−6 in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. Conclusions Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome.

Gut‐directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown.

Assessment of normal bowel habits in the general adult population: the Popcol study.

Abstract Objective. Defining normal stool habit is important when evaluating diarrhoea or constipation, but common confounders such as irritable bowel syndrome (IBS) or the intake of medications with gastrointestinal side effects have not been considered in earlier population based studies defining what is normal. We hypothesized that the exclusion of subjects with common confounders would help to better understand what are “normal bowel habits”. We aimed to prospectively study bowel habits in a carefully studied random sample of the general population. Material and methods. Two hundred and sixty-eight randomly selected subjects between 18 and 70 years completed symptom diaries for one week and were clinically evaluated by a gastroenterologist. They also had a colonoscopy and laboratory investigations to exclude organic disease. Results. One hundred and twenty-four subjects had no organic gastrointestinal abnormality, IBS, or relevant medication; 98% of them had between three stools per day and three per week. Seventy-seven percent of all stools were normal, 12% hard, and 10% loose in consistency. Urgency was reported by 36%; straining by 47% and incomplete defecation by 46%. After the exclusion of subjects with organic abnormalities, women had significantly more symptoms than men in terms of abdominal pain, bloating, constipation, urgency, and feeling of incomplete evacuation but these gender differences disappeared after excluding subjects with IBS. Conclusions. This study confirms that normal stool frequency is between three per week and three per day. We could not demonstrate any gender or age differences in terms of stool frequency, defecatory symptoms or abdominal bloating. Some degree of urgency, straining, and incomplete evacuation should be considered normal.

Pre‐experimental stress in patients with irritable bowel syndrome: high cortisol values already before symptom provocation with rectal distensions

Abstract  Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se. In twenty‐four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment (P = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls (P = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation (P = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.

Evaluation of the sacroanal motor pathway by magnetic and electric stimulation in patients with fecal incontinence.

PURPOSE: The aim of this controlled study was to examine whether it was feasible to use magnetic stimulation as a new diagnostic tool to evaluate the motor function of the sacral roots and the pudendal nerves in patients with fecal incontinence. PATIENTS AND METHODS: Nineteen consecutive patients (17 females) with a median age of 67 (range, 36–78) years referred for fecal incontinence and 14 healthy volunteers (six females) with a median age of 42 (range, 23–69) years were examined. Latency times of the motor response of the external anal sphincter were measured after electric transrectal stimulation of the pudendal nerve and magnetic stimulation of the sacral roots. RESULTS: The success rates of pudendal nerve terminal motor latency and sacral root terminal motor latency measurements were 100 and 85 percent, respectively, in the control group and 94 and 81 percent, respectively, in the fecal incontinence group. Median left pudendal nerve terminal motor latency was 1.88 (range, 1.4–2.9) milliseconds in the control group and 2.3 (range, 1.8–4) milliseconds in the fecal incontinence group (P<0.006). Median right pudendal nerve terminal motor latency was 1.7 (range, 1.3–3.4) milliseconds in the control group and 2.5 (range, 1.7–6) milliseconds in the fecal incontinence group (P<0.003). Median left sacral root terminal motor latency was 3.3 (range, 2.1–6) milliseconds in the control group and 3.7 (range, 2.8–4.8) milliseconds in the fecal incontinence group (P<3 0.03). Median right sacral root terminal motor latency was 3 (range, 2.6–5.8) milliseconds in the control group and 3.9 (range, 2.5–7.2) milliseconds in the fecal incontinence group (P=0.15). CONCLUSIONS: Combined pudendal nerve terminal motor latency and sacral root terminal motor latency measurements may allow us to study both proximal and distal pudendal nerve motor function in patients with fecal incontinence. Values of sacral root terminal motor latency have to be interpreted cautiously because of the uncertainty about the exact site of magnetic stimulation and the limited magnetic field strength.

Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome

Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease

Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy.

Association between bowel symptoms, symptom severity, and quality of life in Swedish patients with fecal incontinence.

Abstract Objectives. The association between abdominal symptoms, disease severity of fecal incontinence (FI), and quality of life (QoL) is not yet clear. We hypothesized that it would become clearer by prospective diary data. We also aimed to compare QoL of FI patients with ulcerative colitis (UC) patients in relapse and remission. Material and methods. Sixty-five consecutive female patients with FI recorded bowel symptoms prospectively on diary cards. QoL was evaluated with the disease specific short health scale questionnaire (SHS). Patients with UC in remission and relapse were used as a reference group regarding SHS. Results. FI patients had median 3.5 leakage episodes/week. In all, 48% of bowel movements were associated with urgency. Urgency was correlated to decreased QoL according to SHS domains: symptoms (Rho = 0.54, p = 0.0002), function (Rho = 0.48, p = 0.0008), and disease related worry (Rho = 0.32, p = 0.027). Abdominal pain and bloating, reported by nearly half of patients, correlated to deceased QoL but not to number of leakages. QoL of patients with FI compared to UC in active phase (n = 35) was similar. FI patients had decreased QoL compared to UC in remission (n = 94) in all dimensions of SHS: symptoms (p < 0.0001), function (p < 0.0001), disease related worry (p < 0.0001), and general well being (p = 0.03). Conclusion. Urgency and irritable bowel syndrome (IBS)-like symptoms were associated with decreased QoL in FI. Therefore, IBS should be considered as an important confounding factor in FI QoL studies. QoL in patients with FI was considerably decreased, in a similar extent as in patients with UC in relapse.