Treating Fecal Incontinence: An Unmet Need in Primary Care Medicine

Fecal incontinence affects up to 36% of primary care patients. Although effective treatments are available, doctors rarely screen for this condition and patients seldom volunteer complaints of fecal incontinence. Conservative management yields 60% improvement in symptoms and continence in 20% of patients. Referrals are currently being accepted for studies seeking to improve case detection and to support conservative management or self-care

Biomarkers to distinguish functional constipation from irritable bowel syndrome with constipation

Treatments for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) differ, but symptom criteria do not reliably distinguish between them; some regard FC and IBS-C as parts of a single constipation spectrum. Our goal was to review studies comparing FC and IBS-C to identify possible biomarkers that separate them. A systematic review identified 15 studies that compared physiologic tests in FC vs IBS-C. Pain thresholds were lower in IBS-C than FC for 3/5 studies and not different in 2/5. Colonic motility was decreased more in FC than IBS-C for 3/3 studies, and whole gut transit was delayed more in FC than IBS-C in 3/8 studies and not different in 5/8. Pelvic floor dyssynergia was unrelated to diagnosis. Sympathetic arousal, measured in only one study, was greater in IBS-C than FC. The most reliable separation of FC from IBS-C was shown by a novel new magnetic resonance imaging technique described in this issue of the journal. These authors showed that drinking one liter of polyethylene glycol laxative significantly increased water content in the small intestine, volume of contents in the ascending colon, and time to first evacuation in FC vs IBS-C; and resulted in less colon motility and delayed whole gut transit in FC compared to IBS-C. Although replication is needed, this well-tolerated, non-invasive test promises to become a new standard for differential diagnosis of FC vs IBS-C. These data suggest that FC and IBS-C are different disorders rather than points on a constipation spectrum

Update on Rome IV Criteria for Colorectal Disorders: Implications for Clinical Practice

Purpose of Review: The purpose of the review was to provide an update of the Rome IV criteria for colorectal disorders with implications for clinical practice. Recent Findings: The Rome diagnostic criteria are expert consensus criteria for diagnosing functional gastrointestinal disorders (FGIDs). The current version, Rome IV, was released in May of 2016 after Rome III had been in effect for a decade. It is the collective product of committees that included more than 100 leading functional GI experts. For functional bowel and anorectal disorders, the majority of changes relative to Rome III are relatively minor and will have little impact on clinical practice. However, notable changes with potential impact on clinical practice and research include the changes in the diagnostic criteria for IBS, the modified approach for subtyping of IBS, the view on functional bowel disorders as a spectrum of disorders, and the new definition of fecal incontinence. Summary: New features in the Rome IV diagnostic criteria for functional bowel and anorectal disorders will likely have modest influence on clinical practice, with a few exceptions

Patient preferences for endpoints in fecal incontinence treatment studies

Background: Randomized controlled trials of treatments for fecal incontinence (FI) are difficult to compare because case definitions and study endpoints vary. Our aims were to assess patient perspectives on the case definition for FI and how treatment success should be measured. Methods: In Phase 1, 28 FI patients participated in anonymous on-line focus groups, and in Phase 2, 186 people with FI, stratified by gender, race, and age completed an online survey. Key Results: Focus group participants described frequency and urgency as the most important characteristics for defining FI. Most (80%) thought staining of underwear constitutes FI, but only 33% thought gas leakage was FI. When asked how the success of treatment should be defined, 77% said by a reduction in frequency or complete cure, but less than half thought a 50% reduction in frequency was enough. When asked how much reduction would be needed, responses averaged 80%. The Phase 2 survey confirmed that frequency, urgency, and intestinal discomfort are the most important characteristics for case definition, and that success should be defined by at least a 75% decrease in frequency. A 50% reduction was an acceptable endpoint for 58% overall but only 26% for those aged ≥65. “Adequate relief” was acceptable to 78%. Conclusions and Inferences: Inclusion criteria for trials should specify a minimum frequency of FI. Most patients would require a ≥75% reduction in FI frequency to call a treatment successful but young adults and those with more severe FI would accept a ≥50% reduction as meaningful

Balancing Clinical Objectives with Patient Centered Care

This poster is a reflection focuses on the challenges of balancing the medical needs of a patient and their preferences in an interdisciplinary health care setting. Students from UNE\u27s Physician Assistant, Osteopathic Medicine, Social Work, Dental Medicine, and Nursing programs collaborated with Allopathic Medicine and Podiatric Medicine students from Rosalind Franklin University Medical School as a virtual health care team to care for a patient with long-covid

Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids

Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map™ dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n\ua0=\ua07), PBS (n\ua0=\ua04) or LPS (n\ua0=\ua03) presented distinct gene expression profiles, with some overlap (R2Y\ua0=\ua00.70, Q2=\ua00.43). Addition of fecal supernatants from healthy subjects and IBS patients (n\ua0=\ua09) gave rise to different gene expression profiles of the colonoid monolayers (R2Y\ua0=\ua00.79, Q2=\ua00.64). Genes (n\ua0=\ua022) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions

Prevalence of Rome IV Functional Bowel Disorders Among Adults in the United States, Canada, and the United Kingdom

Background & Aims: Little is known about the population prevalence or demographic distributions of Rome IV functional bowel disorders (FBDs) or their effects on quality of life. We examined these in a multinational survey. Methods: We analyzed data from a population-based survey of adults in the United States, Canada, and United Kingdom (5931 valid responders; 49.2% female; mean age, 47.4 years; range, 18–92 years). The survey included the Rome IV Diagnostic Questionnaire, Rome III irritable bowel syndrome (IBS) and constipation questions, and the SF-8 quality of life questionnaire. Results: The prevalence values of census-adjusted Rome IV FBDs were similar among the 3 countries; ranges were: 4.4%–4.8% for IBS, 7.9%–8.6% for functional constipation, 3.6%–5.3% for functional diarrhea, 2.0%–3.9% for functional bloating or distention, 1.1%–1.9% for opioid-induced constipation, 7.5%–10.0% for unspecified FBDs, and 28.6%–31.7% for any Rome IV FBD. FBDs were less common in older individuals, and all except functional diarrhea were more common in women. IBS was only half as prevalent by Rome IV as by Rome III criteria (4.6% vs 9.0% overall), primarily due to higher Rome IV minimum pain frequency. Functional diarrhea and functional constipation were more prevalent by Rome IV than Rome III criteria. Subjects with FBD had significant reductions in quality of life and reported more gastrointestinal doctor consultations than other subjects. Conclusions: More than 1 in 4 adults in the general population meet the Rome IV criteria for FBDs. These disorders affect quality of life and increase use of gastrointestinal health care. The switch from Rome III to Rome IV criteria reduces the prevalence of IBS by half, but increases the prevalence of functional constipation and functional diarrhea

A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome

Although incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18–58)) and 20 HC (60% female, mean age 26.8 (range 23–41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based “permeability cluster” was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based “immune-enteroendocrine cluster” was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease

Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids

Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography–mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases