ABSTRACT
OBJECTIVES: This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care. METHODS: Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman's correlation was used to assess the association between changes in PPI dose and patient-reported outcomes. RESULTS: A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 - 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 - -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 - 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02). CONCLUSION: In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.
Continuous and on-demand prescription increase in proton pump inhibitor consumption equally in real-world settings and did not result in different outcomes.Reaching a sufficient dose of proton pump inhibitor to reduce reflux symptom burden improves quality of life in patients with gastroesophageal reflux disease.
Subject(s)
Gastroesophageal Reflux , Primary Health Care , Proton Pump Inhibitors , Quality of Life , Humans , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Gastroesophageal Reflux/drug therapy , Female , Male , Middle Aged , Adult , Patient Reported Outcome Measures , Aged , Europe , Treatment Outcome , Symptom BurdenABSTRACT
The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabA's binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.
ABSTRACT
BACKGROUND: The etiopathogenesis of diverticular disease is unknown. OBJECTIVE: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study. METHODS: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not. RESULTS: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027). CONCLUSIONS: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.
Subject(s)
Diverticular Diseases , Diverticulitis, Colonic , Diverticulitis , Diverticulosis, Colonic , Diverticulum , Gastrointestinal Microbiome , Adult , Humans , Diverticulitis, Colonic/complications , Diverticulosis, Colonic/complications , Cohort Studies , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Diverticulitis/complications , Diverticulum/complications , Diverticular Diseases/complications , Colonoscopy/adverse effectsABSTRACT
Background: Ulcerative colitis (UC) is a debilitating inflammatory bowel disease. Present knowledge regarding UC disease progression over time is limited. Objective: To assess UC progression to severe disease along with disease burden and associated factors. Methods: Electronic medical records linked with Swedish national health registries (2005-2015) were used to identify disease progression of UC. Odds of all-cause and disease-related hospitalization within 1 year were compared between patients with disease progression and those without. Annual indirect costs were calculated based on sick leave, and factors related to UC progression were examined. Results: Of the 1,361 patients with moderate UC, 24% progressed to severe disease during a median of 5.2 years. Severe UC had significantly higher odds for all-cause (OR [odds ratio] 1.47, 95% CI [confidence interval]: 1.12-1.94, P < 0.01) and UC-related hospitalization (OR 2.47, 95% CI: 1.76-3.47, P < 0.0001) compared to moderate disease. Average sick leave was higher in patients who progressed compared to those who did not (64.4 vs 38.6 days, P < 0.001), with higher indirect costs of 151,800 SEK (16,415 ) compared with 92,839 SEK (10,039 ) (P < 0.001), respectively. UC progression was related to young age (OR 1.62, 95% CI: 1.17-2.25, P < 0.01), long disease duration (OR 1.09, 95% CI: 1.03-1.15, P < 0.001), and use of corticosteroids (OR 2.49, 95% CI: 1.67-3.72, P < 0.001). Conclusion: Disease progression from moderate to severe UC is associated with more frequent and longer hospitalizations and sick leave. Patients at young age with long disease duration and more frequent glucocorticosteroid medication are associated with progression to severe UC.
Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/therapy , Retrospective Studies , Electronic Health Records , Cost of Illness , Disease ProgressionABSTRACT
Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter pylori/genetics , Helicobacter Infections/microbiology , Black People/genetics , Africa , MutationABSTRACT
BACKGROUND: An individual's drive to seek medical help remains a complex behavioural process, incorporating psychological, social and symptom-specific factors. Within irritable bowel syndrome (IBS), gastrointestinal symptoms only predict a small portion of the high healthcare-seeking experienced. AIM: To examine the moderating role of quality of life (QoL) domains on this relationship to help explain the variance observed. METHODS: This is an analysis of a Swedish population-based prospective study of healthcare use over a 12-year period. At baseline, gastrointestinal symptoms were measured with the valid Gastrointestinal Symptom Rating Scale, and QoL via the SF-36. 1159 subjects (57% female; mean age 48.6 years) had their health records matched with the initial survey. 164 were classified as IBS by Rome II criteria. Negative binomial or logistic models were fit to evaluate the moderating effect of particular QoL domains on the relationship between gastrointestinal symptoms and prospective healthcare utilisation. RESULTS: Gastrointestinal symptoms were associated with prospective healthcare use, but moderation in this relationship by particular QoL domains was not supported; most models did not reach statistical significance. Furthermore, the impact of IBS status did not alter the moderation hypotheses. CONCLUSIONS: Particular QoL domains did not impact the relationship between gastrointestinal symptoms on prospective healthcare seeking. Future research should continue to examine other psychological, social and symptom variables to identify predictors of high healthcare consumers in IBS.
Subject(s)
Irritable Bowel Syndrome , Quality of Life , Female , Humans , Irritable Bowel Syndrome/diagnosis , Male , Middle Aged , Patient Acceptance of Health Care , Prospective Studies , Quality of Life/psychology , Surveys and QuestionnairesABSTRACT
Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
ABSTRACT
PPIs (Proton-pump inhibitors) offers the best treatment for acid related diseases. The predominant indications for PPI prescription are: GERD eradication of H. pylori-infection in combination with antibiotics H. pylori-negative peptic ulcer healing of and prophylaxis against NSAID/COXIB--induced gastroduodenal lesions acid hypersecretory states such as Zollinger-Ellisons syndrome. The market for PPIs continues to expand in most countries. A significant over- and misuse of PPIs prevails in hospital care as well as in general practice. The predominant reasons for and mechanisms behind the over- and misuse of PPIs are well recognised. The most important consequences of this overprescription of PPIs are increasing medical costs and risk for long-term adverse side effects. Continued education and dedicated information are key factors to guide physicians, medical personnel and patients to adopt to generally accepted principles for and balanced use of PPIs.
Subject(s)
Helicobacter Infections , Peptic Ulcer , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Helicobacter Infections/drug therapy , Humans , Peptic Ulcer/chemically induced , Peptic Ulcer/prevention & control , Proton Pump Inhibitors/adverse effectsSubject(s)
Dyspepsia , Gastritis , Irritable Bowel Syndrome , Dyspepsia/epidemiology , Dyspepsia/etiology , Humans , Tobacco UseABSTRACT
BACKGROUND: Functional gastrointestinal disorders (FGIDs) are diagnosed according to expert consensus criteria based on recall of symptoms over periods of 3 months or longer. Whether the expert opinion concords with underlying disease process and whether individual recall is accurate are both in doubt. This study aimed to identify naturally occurring clusters of individuals with respect to symptom pattern, evaluate their significance, compare cluster profiles with expert opinion and evaluate their temporal stability. METHODS: As part of a random population study of FGID-related symptoms, we first explored the use of prospective stool and symptom diaries combined with empirical grouping of individuals into clusters using nonhierarchical cluster analysis. RESULTS: The analysis identified two clusters of individuals, one of which was characterized by elevated scores on all domains of symptoms (26% of the sample) and one that was low to average on all domains (74% of the sample). Cluster membership was found to be stable over a long interval. Clusters were found to differ on most domains of quality-of-life (d = 0.46-0.74), self-rated health (d = -0.42) and depression (d = -0.42) but not anxiety. Prevalence of clinically diagnosed irritable bowel syndrome (IBS) was higher in the more impacted cluster (33%) compared with the healthy cluster (13%; P < 0.0001). CONCLUSION: A naturalistic classification of individuals challenges consensus criteria in showing that some IBS individuals have a symptom experience not unlike health. The proposed approach has demonstrated temporal stability over time, unlike consensus criteria. A naturalistic disease classification system may have practical advantages over consensus criteria when supported by a decision-analytic system.
Subject(s)
Gastrointestinal Diseases , Irritable Bowel Syndrome , Anxiety , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Humans , Independent Living , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/epidemiology , Prospective StudiesABSTRACT
Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32-37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13-2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.
Subject(s)
Eosinophils , Esophageal Mucosa/cytology , Esophageal Mucosa/pathology , Gastroesophageal Reflux/pathology , Intraepithelial Lymphocytes , Neutrophils , Adult , Aged , Eosinophils/cytology , Eosinophils/pathology , Female , Humans , Intraepithelial Lymphocytes/cytology , Intraepithelial Lymphocytes/pathology , Male , Middle Aged , Neutrophils/cytology , Neutrophils/pathology , Reference ValuesABSTRACT
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.
Subject(s)
Dyspepsia , Irritable Bowel Syndrome , Diarrhea , Dyspepsia/epidemiology , Dyspepsia/etiology , Female , Humans , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/etiology , Male , Middle Aged , Smoking/adverse effects , Surveys and Questionnaires , Sweden/epidemiologyABSTRACT
INTRODUCTION: The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety. METHODS: Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1st (D1) and 2nd portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value. RESULTS: The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046). CONCLUSION: Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD.
Subject(s)
Dyspepsia , Eosinophilia , Anxiety , Endoscopy, Gastrointestinal , Eosinophilia/diagnosis , Eosinophilia/pathology , Female , Follow-Up Studies , Humans , Male , Middle AgedABSTRACT
To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10-10 < P < 5 × 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Subject(s)
Gastrointestinal Microbiome/physiology , Genetic Variation , Quantitative Trait Loci , Adolescent , Adult , Bifidobacterium/genetics , Child , Child, Preschool , Cohort Studies , Female , Gastrointestinal Microbiome/genetics , Genome-Wide Association Study , Humans , Lactase/genetics , Linkage Disequilibrium , Male , Mendelian Randomization Analysis , Metabolism/genetics , RNA, Ribosomal, 16SABSTRACT
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.
Subject(s)
Dyspepsia/epidemiology , Gastroesophageal Reflux/epidemiology , Abdominal Pain/epidemiology , Adult , Aged , Aged, 80 and over , Female , Heartburn/epidemiology , Humans , Incidence , Logistic Models , Male , Middle Aged , Postprandial Period , Prevalence , Sweden/epidemiology , Young AdultABSTRACT
Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
Subject(s)
Bacteroides , Feces/microbiology , Gastrointestinal Microbiome , Ileum/microbiology , Intestinal Mucosa/microbiology , Intestine, Large/microbiology , Bacteroides/classification , Bacteroides/genetics , Bacteroides/metabolism , Female , Humans , MaleABSTRACT
INTRODUCTION: Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity. METHODS: In a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota. RESULTS: Microbiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001). DISCUSSION: In this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.
Subject(s)
Dysbiosis/microbiology , Gastric Mucosa/pathology , Gastritis/microbiology , Gastrointestinal Microbiome , Helicobacter Infections/epidemiology , Adult , Aged , Biopsy , Chronic Disease , DNA, Bacterial/isolation & purification , Dysbiosis/diagnosis , Dysbiosis/epidemiology , Dysbiosis/pathology , Female , Follow-Up Studies , Gastric Mucosa/diagnostic imaging , Gastric Mucosa/microbiology , Gastritis/diagnosis , Gastritis/epidemiology , Gastritis/pathology , Gastroscopy , Helicobacter Infections/diagnosis , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/genetics , Helicobacter pylori/isolation & purification , Humans , Longitudinal Studies , Male , Middle Aged , Prevalence , RNA, Ribosomal, 16S/genetics , Sweden/epidemiologyABSTRACT
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.
Subject(s)
Constipation/diagnosis , Diarrhea/diagnosis , Irritable Bowel Syndrome/diagnosis , Severity of Illness Index , Adolescent , Adult , Aged , Constipation/etiology , Constipation/psychology , Diarrhea/etiology , Diarrhea/psychology , Factor Analysis, Statistical , Female , Humans , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/psychology , Male , Middle Aged , Psychometrics/statistics & numerical data , Quality of Life , Surveys and Questionnaires/statistics & numerical data , Sweden , Young AdultABSTRACT
INTRODUCTION: Histopathological alterations in the ileum and colon in irritable bowel syndrome (IBS) are controversial, and normal values are poorly established. We hypothesized that changes in mucosal immune cells characterize IBS and key changes in immune composition are associated with the mucosa-associated microbiota (MaM). METHODS: A nested case-control study (48 IBS and 106 controls included) from 745 colonoscopy participants in a random population sample. Intraepithelial lymphocytes (IELs)/100 enterocytes and eosinophils/5 nonoverlapping high-power fields counted; mast cells identified by immunocytochemistry (CD117)/5 high-power fields. Paneth cells quantified per 5 crypts. 16S rRNA gene amplicon sequencing performed on available sigmoid MaM, n = 55 and fecal microbiota, n = 20. Microbiota profiles compared between samples with high and low IEL counts. RESULTS: IBS had increased IELs in the terminal ileum (relative risk ratio = 1.70, 95% confidence interval 1.08-2.76, P = 0.022 adjusted for age, sex, and smoking). Cecal IELs were increased in IBS-diarrhea (relative risk ratio = 2.03, 95% confidence interval 1.13-3.63, P = 0.017). No difference was observed in alpha diversity of MaM or fecal microbiota based on IEL count. There was no difference in beta diversity of the MaM according to IEL count in the terminal ileal (TI) (P = 0.079). High TI IEL counts associated with a significant expansion of the genus Blautia (P = 0.024) and unclassified Clostridiales (P = 0.036) in colon MaM. DISCUSSION: A modest but significant increase in IELs was observed in IBS vs. controls in a population-based setting. Subtle TI and cecal inflammation may play a pathogenic role in IBS but needs confirmation. Modest but discernible differences in the colonic MaM were seen according to TI IEL count but not IBS status.