An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years: A Prospective Population-Based Study in Sweden.

INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing. METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21-79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22-80 years, rr = 87%), 1995 (n = 1,139, 20-85 years, rr = 76%), and 2011 (n = 1,175, 20-93 years, rr = 63%). RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60-4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42-1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50-2.73). DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.

No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population.

OBJECTIVE: The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings. DESIGN: The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases). RESULTS: While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R²=0.255, p<3E-11) as was diversity (R²=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals. CONCLUSIONS: No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.

Isolates from Colonic Spirochetosis in Humans Show High Genomic Divergence and Potential Pathogenic Features but Are Not Detected Using Standard Primers for the Human Microbiota.

Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the Brachyspira aalborgi type strain, 513A. Also, 16S analysis of the mucosa-associated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species Brachyspira pilosicoli; all remaining isolates were of the species Brachyspira aalborgi Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulence-associated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect Brachyspira due to primer incompatibility.IMPORTANCE This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.

Colonoscopy findings in high-risk individuals compared to an average-risk control population.

BACKGROUND AND AIMS: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. METHODS: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. RESULTS: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. CONCLUSIONS: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.

Prevalence of colonic neoplasia and advanced lesions in the normal population: a prospective population-based colonoscopy study.

OBJECTIVE: There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. METHODS: A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. RESULTS: Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. CONCLUSION: One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.

Prospective diary evaluation of unexplained abdominal pain and bowel dysfunction: a population-based colonoscopy study.

INTRODUCTION: Diagnostic criteria for irritable bowel syndrome (IBS) have not been validated by prospective symptom diary. We investigated the bowel patterns in community subjects with and without non-organic abdominal pain, and compared the symptoms with subjects fulfilling the Rome II criteria (IBS). METHODS: From the Swedish population register, a random sample completed an abdominal symptom questionnaire. Responders were subsequently invited for a clinical evaluation and offered a colonoscopy regardless of whether they had abdominal symptoms or not. A total of 268 subjects underwent colonoscopy, clinical evaluation by gastroenterologist, laboratory investigations, and completed the Rome questionnaire and prospective gastrointestinal (GI) symptom diaries for 1 week. Twenty-three subjects of 268 were excluded due to organic GI disease. RESULTS: Subjects recorded 2,194 bowel movements and 370 abdominal pain episodes on 1,504 days. Subjects with pain in the diary (n = 81) had higher stool frequency (P = 0.01), more urgency (P = 0.0002), feelings of incomplete evacuation (P = 0.0002), nausea (P = 0.0009), and abdominal bloating (P = 0.0005) than subjects without pain (n = 151). Twenty-eight subjects (12%) fulfilled the Rome II criteria for IBS. Together, they had 96 pain episodes but only 4% were improved by defecation; 29% of the pain episodes started or worsened after a meal. Subjects with IBS and other subjects with non-organic abdominal pain (n = 64) exhibited no differences in terms of the proportions of pain episodes improved by defecation, bloating, stool frequency, consistency, or defecatory symptoms. CONCLUSIONS: Current criteria for IBS that rely on recall of the relationship between abdominal pain and bowel disturbance may overcall this association when measured prospectively.

Role of smoking in functional dyspepsia and irritable bowel syndrome: three random population-based studies.

BACKGROUND: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients. AIM: To assess if smoking is an independent risk factor for FD and IBS. METHODS: Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex. RESULTS: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed. CONCLUSION: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.

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

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.

Discriminant and convergent validity of the GSRS-IBS symptom severity measure for irritable bowel syndrome: A population study.

BACKGROUND: The Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) is a 13-item measure of IBS symptom severity. The scale has been used in several studies, but its psychometric properties have been insufficiently investigated and population-based data are not available. OBJECTIVE: The objective of this article is to establish the factor structure and discriminant and convergent validity of the GSRS-IBS. METHODS: The study was based on a Swedish population sample (the Popcol study), of which 1158 randomly selected participants provided data on the GSRS-IBS. We used confirmatory factor analysis (CFA) and compared total and subscales scores in different groups, including IBS diagnostic status, treatment-seeking behavior, and predominant bowel habits. The GSRS-IBS scores were also correlated with quality of life indexes. RESULTS: The sample included 164 participants with a confirmed Rome III IBS diagnosis and 994 participants without the disease. The CFA confirmed the subscales with one exception, in which the incomplete bowel-emptying item belonged to the constipation subscale rather than the diarrhea subscale. The GSRS-IBS total score and subscales were associated with diagnostic status, treatment-seeking behavior, and quality of life dimensions. The relevant subscales scores also differed between the diarrhea- and constipation-predominant subtypes of IBS. CONCLUSION: The GSRS-IBS total score and subscales have high discriminant and convergent validity. The CFA confirmed the overall validity of the subscales but suggest that a sense of incomplete emptying belongs to the constipation rather than the diarrhea symptom cluster. We conclude that the GSRS-IBS is an excellent measure of IBS symptom severity in the general population.

Function and dysfunction of the colon and anorectum in adults: working team report of the Swedish Motility Group (SMoG).

Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.

Doubtful outcome of the validation of the Rome II questionnaire: validation of a symptom based diagnostic tool.

BACKGROUND: Questionnaires are used in research and clinical practice. For gastrointestinal complaints the Rome II questionnaire is internationally known but not validated. The aim of this study was to validate a printed and a computerized version of Rome II, translated into Swedish. Results from various analyses are reported. METHODS: Volunteers from a population based colonoscopy study were included (n = 1011), together with patients seeking general practice (n = 45) and patients visiting a gastrointestinal specialists' clinic (n = 67). The questionnaire consists of 38 questions concerning gastrointestinal symptoms and complaints. Diagnoses are made after a special code. Our validation included analyses of the translation, feasibility, predictability, reproducibility and reliability. Kappa values and overall agreement were measured. The factor structures were confirmed using a principal component analysis and Cronbach's alpha was used to test the internal consistency. RESULTS AND DISCUSSION: Translation and back translation showed good agreement. The questionnaire was easy to understand and use. The reproducibility test showed kappa values of 0.60 for GERS, 0.52 for FD, and 0.47 for IBS. Kappa values and overall agreement for the predictability when the diagnoses by the questionnaire were compared to the diagnoses by the clinician were 0.26 and 90% for GERS, 0.18 and 85% for FD, and 0.49 and 86% for IBS. Corresponding figures for the agreement between the printed and the digital version were 0.50 and 92% for GERS, 0.64 and 95% for FD, and 0.76 and 95% for IBS. Cronbach's alpha coefficient for GERS was 0.75 with a span per item of 0.71 to 0.76. For FD the figures were 0.68 and 0.54 to 0.70 and for IBS 0.61 and 0.56 to 0.66. The Rome II questionnaire has never been thoroughly validated before even if diagnoses made by the Rome criteria have been compared to diagnoses made in clinical practice. CONCLUSION: The accuracy of the Swedish version of the Rome II is of doubtful value for clinical practice and research. The results for reproducibility and reliability were acceptable but the outcome of the predictability test was poor with IBS as an exception. The agreement between the digital and the paper questionnaire was good.

Gastrointestinal recall questionnaires compare poorly with prospective patient diaries for gastrointestinal symptoms: data from population and primary health centre samples.

BACKGROUND: Clinical understanding of gastrointestinal symptoms is commonly based on patient reports of symptom experience. For diagnosis and treatment choices to be appropriate, symptom reports need to be accurate. We examined the agreement between questionnaire recall and prospective diary enumeration of symptoms relevant to the irritable bowel syndrome. PATIENTS AND METHODS: Data are reported from a randomly selected general population sample (n=238) and also a primary healthcare centre (PHC) sample (n=503, 10 PHCs). All the patients completed the questionnaires, which included Rome III-qualifying irritable bowel syndrome items and a stool and symptom diary over either 7 or 14 days. Agreement between retrospective questionnaire reports and prospective diaries was evaluated. RESULTS: Concordance between questionnaires and diaries was highest for the simple construct of the occurrence of abdominal pain, although after adjusting for possible chance, agreement was only moderate in the general population sample. More complex constructs, such as pain relieved by defecation, yielded poorer concordance. In general, concordance was stronger among PHC respondents than in the general population sample. CONCLUSION: Concordance between questionnaires and diaries was generally poor and related to the complexity of the symptom construct and the type of respondent. The information used to classify individuals based on patient self-report may be unreliable, and therefore, more effort is needed to develop data collection instruments.

How individuals with the irritable bowel syndrome describe their own symptoms before formal diagnosis.

AIM: To investigate how individuals fulfilling the Rome II criteria for irritable bowel syndrome (IBS) spontaneously described their symptoms. METHOD: From a general population, 1,244 randomly sampled adults were asked to describe their gastrointestinal symptoms (if any) verbally, in their own words, at a semi-structured interview. Their own descriptions were sorted into five symptom clusters. The participants independently completed a written questionnaire (the Rome II Modular Questionnaire (RMIIMQ)). RESULTS: A total of 601 participants reported at least one gastrointestinal symptom, and 128 had IBS according to the RMIIMQ. After exclusion of organic causes, previously diagnosed IBS, or additional gastrointestinal diagnosis, 81 participants with IBS according to RMIIMQ remained. Five participants (6%) described symptoms included in the full definition of IBS, but none fulfilled the Rome II criteria completely. Abdominal pain or other IBS-related symptoms were reported by 64 (79%), and 12 (15%) did not report any IBS-like symptom. CONCLUSION: Previously undiagnosed individuals, who fulfil criteria for Rome II-IBS, often express their complaints in words that do not fit into the current diagnostic criteria.

Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden.

Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (P = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.

A randomly selected population sample undergoing colonoscopy: prevalence of the irritable bowel syndrome and the impact of selection factors.

OBJECTIVE: To analyse the epidemiology of irritable bowel syndrome (IBS) symptoms in a random sample of the general population and in a subsample consenting to a colonoscopy, and to what extent this introduces symptom selection bias. MATERIALS AND METHODS: Overall, 3347 randomly selected Swedish adults aged 18-70 years were mailed the validated Abdominal Symptom Questionnaire (ASQ). Responders (n=2293; 68.5%) were contacted by phone, and 745 consented to a colonoscopy. All nonresponders were contacted by phone; 265 were reached and asked seven key ASQ questions. Colonoscopy participants also completed the Rome II Modular Questionnaire. RESULTS: The prevalence of IBS on the basis of the mailed ASQ (troublesome abdominal pain and bowel disturbance in the past 3 months) was 26.2% [95% confidence interval (CI): 24.4-28.0] among the ASQ responders and 36.6% (95% CI: 33.2-40.1) among the colonoscopy participants (P<0.001). Nonresponders had a lower prevalence of IBS (15.8%; 95% CI: 11.4-20.3, P<0.001) than ASQ responders. Colonoscopy participants were slightly older than noncolonoscoped participants completing the ASQ (P<0.001), but men and women were equally represented and no significant socioeconomic differences were identified. The prevalence of IBS was 14.8% (95% CI: 12.2-17.5) on the basis of the Rome II Modular Questionnaire in colonoscopy participants and 14.5% (95% CI: 11.9-17.2) when visible inflammatory disease was excluded. Of the colonoscopy participants, 31.9% (95% CI: 28.5-35.3) were symptom free. CONCLUSION: IBS symptoms are common and rarely explained by visible inflammatory disease or cancer. There was a modest selection bias by IBS in participants accepting a screening colonoscopy, but still, one-third were symptom free. Thus, conclusions for the general population can be made from findings in the study cohort.