BACKGROUND & AIMS:The low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols (FODMAP) diet (LFD) and rifaximin are effective in <50% individuals with irritable bowel syndrome (IBS), highlighting the need to identify predictors of treatment response. We therefore conducted a randomized controlled trial comparing LFD and rifaximin to identify microbial predictors of response. METHODS:Sixty-five adults with diarrhea-predominant IBS (IBS-D) were randomized to LFD or rifaximin for 5 weeks. Primary endpoints were changes in mean daily abdominal pain and bloating at week 5 vs baseline. Secondary endpoints included changes in IBS Symptom Severity Score and Bristol Stool Form Scale at week 5 vs baseline. Exploratory endpoints included responders defined as ≥30% reduction in abdominal pain or bloating. Stool samples collected at weeks 0, 2, 4, and 5 underwent 16S rRNA sequencing, and glucose breath testing (BT) was performed at weeks 0 and 5. RESULTS:Both LFD and rifaximin significantly improved abdominal pain (-0.29 with LFD vs -0.24 points/week with rifaximin); bloating (-0.29 vs -0.19 per week); and IBS Symptom Severity Score (-14.2 vs -13.3 per week) at week 5 (all P < .0001), with no significant change in Bristol Stool Form Scale. BT results were inconsistent predictors of response, with positive baseline hydrogen BT associated with lower odds of rifaximin response, and methane conversion at week 5 showed discordant associations with rifaximin response. In contrast, distinct baseline taxa were associated with treatment response. LFD responders had lower abundance of putative saccharolytic taxa (Butyricimonas, Bacteroides, Intestinibacter), whereas rifaximin responders were enriched in taxa with putative short-chain fatty acid-producing and bile acid-modifying potential (Ruminococcus, Coprococcus, Odoribacter). Nonresponders exhibited enrichment of putative proteolytic taxa (Bilophila, Alistipes, Prevotella). CONCLUSIONS:LFD and rifaximin are equally effective for IBS-D, with distinct microbial predictors of response. However, these findings require validation before informing personalized treatment approaches. CLINICALTRIALS:gov, Number: NCT03219528.

Fluids sampled from the gastrointestinal (GI) tract are of interest for evaluating the bioequivalence of oral medications, and more generally for evaluating GI-related diseases, and for profiling the individual gut microbiome. Existing options for capturing multiple fluid samples from specific locations in the GI tract are limited and invasive, particularly for the small intestine. Here, we report the development of an ingestible capsule for the collection of multiple fluid samples along the GI tract; we additionally report the use of data from sensors within the capsule to determine the sampling regions. The capsule has an ingestible size of Φ14 × 42 mm3. Within this volume, it includes three separate cartridges that capture and retain samples within capillaries; a stepper motor for positioning the sampling cartridges at a sampling port; a 3-axis accelerometer that enables a new method of correlating sample location; a microcontroller with wireless communication and sensor data storage capabilities; and batteries to power the device. We describe in vitro characterization and in vivo tests performed with canine models that have successfully verified the capabilities of the capsule. Fluid samples from the stomach, small intestine, and colon regions of the GI tract are identified by inertial measurements taken within the capsule, and correlated to measurements of the concentration of mesalamine (a drug used for testing) and the bile salt profile in each region, respectively.

INTRODUCTION:The London classification provides standardization for characterization of disorders of anorectal function, although prevalences and clinical impact of these disorders are unclear. METHODS:An international research consortium was established, including 5 specialist centers. Prospective data were collected in consecutive adults referred for refractory chronic constipation (CC), fecal incontinence (FI), or coexistent CC/FI over 18 months. Patients completed a standardized clinical questionnaire and underwent anorectal physiology tests, which were performed and interpreted using uniform methodology. The prevalence of the London classification was compared between symptom groups (CC, FI, and coexistent CC/FI), equipment types, and sites. Clinical impact was assessed using Cleveland Clinic Constipation and St. Marks Incontinence Scores. RESULTS:Of 1,012 included patients (85.6% women), 30.5% had self-reported CC, 33.2% had FI, and 36.3% had coexistent CC/FI. Rectoanal areflexia was uncommon (3.1%). Disorders of anal tone/contractility (CC: 45.0%; FI: 68.5%; coexistent CC/FI: 63.8%; P < 0.0001) and disorders of rectal sensation (major findings: rectal hyposensitivity, CC: 10.0%; FI: 5.0%; coexistent CC/FI: 11.1%; P = 0.018; rectal hypersensitivity, CC: 3.8%; FI: 9.0%; coexistent CC/FI: 4.9%; P = 0.025) varied between the symptom groups and were associated with symptom severity. Most disorders of rectoanal coordination were found in similar proportions across the symptom groups and were not associated with the severity of CC (median Cleveland Clinic Constipation Score 10-14 in all groups). Prevalences of some disorders differed between equipment types (specifically balloon expulsion test). DISCUSSION:This prospective multicenter study provides information on the prevalence and clinical impact of the London classification and will guide refinement of the current London classification.

Purpose of Review To discuss all the various motility disorders impacting people with Cystic Fibrosis (PwCF) and provide diagnostic and management approaches from a group of pediatric and adult CF and motility experts and physiologists with experience in the management of this disease. Recent Findings Gastrointestinal (GI) symptoms coexist with pulmonary symptoms in PwCF regardless of age and sex. The GI manifestations include gastroesophageal reflux disease, esophageal dysmotility gastroparesis, small bowel dysmotility, small intestinal bacterial overgrowth syndrome, distal idiopathic obstruction syndrome, constipation, and pelvic floor disorders. They are quite debilitating, limiting the patients’ quality of life and affecting their nutrition and ability to socialize. This genetic disorder affects many organ systems and is chronic, potentially impacting fertility and future family planning, requiring a multidisciplinary approach. Summary Our review discusses the treatments of motility disorders in CF, their prevalence and pathophysiology. We have provided a framework for clinicians who care for these patients that can help to guide their clinical management.

BACKGROUND & AIMS:Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS:Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS:ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS:Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Functional constipation (FC) is one of the most frequently encountered gastrointestinal conditions in practice.1 Practice guidelines universally recommend that patients with typical constipation symptoms and no alarm features be treated empirically with dietary/lifestyle interventions and laxative therapy.2,3 Unfortunately, by the time a patient reaches a gastroenterologist, these treatments frequently have already been tried. Anorectal function testing (anorectal manometry [ARM] and balloon expulsion test [BET]) is the next best step in management guidelines in this all-too-common scenario, because treatment can then be targeted toward pelvic floor dysfunction or colon transit abnormalities. Unfortunately, more than 95% of patients continue to take only over-the-counter laxatives and receive empirical dietary advice, whereas fewer than 2% undergo physiologic evaluation to ascertain the cause of their symptoms.4 Indeed, more than 90% of patients desire more effective treatment options. These observations call into question the wisdom of a management strategy that fails to recognize the intrinsic diversity of the constipation universe and reinforces the misguided "one size fits all" empirical treatment strategy.

ABSTRACTBACKGROUND AND AIMSEvaluation for dyssynergia is the most common reason that gastroenterologists refer patients for anorectal manometry, because dyssynergia is amenable to biofeedback by physical therapists. High-definition anorectal manometry (3D-HDAM) is a promising technology to evaluate anorectal physiology, but adoption remains limited by its sheer complexity. We developed a 3D-HDAM deep learning algorithm to evaluate for dyssynergia.METHODSSpatial-temporal data were extracted from consecutive 3D-HDAM studies performed between 2018-2020 at a tertiary institution. The technical procedure and gold standard definition of dyssynergia were based on the London consensus, adapted to the needs of 3D-HDAM technology. Three machine learning models were generated: (1) traditional machine learning informed by conventional anorectal function metrics, (2) deep learning, and (3) a hybrid approach. Diagnostic accuracy was evaluated using bootstrap sampling to calculate area-under-the-curve (AUC). To evaluate overfitting, models were validated by adding 502 simulated defecation maneuvers with diagnostic ambiguity.RESULTS302 3D-HDAM studies representing 1,208 simulated defecation maneuvers were included (average age 55.2 years; 80.5% women). The deep learning model had comparable diagnostic accuracy (AUC=0.91 [95% confidence interval 0.89-0.93]) to traditional (AUC=0.93[0.92-0.95]) and hybrid (AUC=0.96[0.94-0.97]) predictive models in training cohorts. However, the deep learning model handled ambiguous tests more cautiously than other models; the deep learning model was more likely to designate an ambiguous test as inconclusive (odds ratio=4.21[2.78-6.38]) versus traditional/hybrid approaches.CONCLUSIONSBy considering complex spatial-temporal information beyond conventional anorectal function metrics, deep learning on 3D-HDAM technology may enable gastroenterologists to reliably identify and manage dyssynergia in broader practice.

BACKGROUND & AIMS: We performed a clinical trial that aimed to inform the clinical utility of anorectal manometry (ARM) and balloon expulsion time (BET) as up-front tests to predict outcomes with community -based pelvic floor physical therapy as the next best step to address chronic constipation after failing an empiric trial of soluble fiber supplementation or osmotic laxatives.METHODS: We enrolled 60 treatment-naive patients with Rome IV functional constipation failing 2 weeks of soluble fiber supplementation or osmotic laxatives. All patients underwent ARM/BET (London protocol) followed by community-based pelvic floor physical therapy. Outcomes were assessed at baseline and 12 weeks. The primary end point was clinical response (Patient Assessment of Constipation-Symptoms instrument).RESULTS: Fifty-three patients completed pelvic rehabilitation and the post-treatment questionnaire. Contemporary frameworks define dyssynergia on balloon expulsion time and dyssynergic patterns (ARM), but these parameters did not inform clinical outcomes (area under the curve [AUC], <0.6). Squeeze pressure (>192.5 mm Hg on at least 1 of 3 attempts; sensitivity, 47.6%; specificity, 83.9%) and limited squeeze duration (inability to sustain 50% of squeeze pressure for >20 seconds; sensitivity, 71.4%; specificity, 58.1%) were the strongest predictors of clinical outcomes. Combining BET with squeeze duration (BET greater than 6.5 seconds and limited squeeze duration) improved predictive accuracy (AUC, 0.75; 95% CI, 0.59-0.90). BET poorly predicted outcomes as a single test (AUC, 0.54; 95% CI, 0.38-0.69).CONCLUSIONS: Using ARM to evaluate squeeze profiles, rather than dyssynergia, appears useful to screen patients with chronic constipation for up-front pelvic floor physical therapy based on likelihood of response. BET appears noninformative as a single screening test (ClinicalTrials.gov: NCT04159350).

BACKGROUND & AIMS:Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy. METHODS:We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction, >0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction, >1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition). RESULTS:Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P < .001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P < .001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or >120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained >13 seconds) but likely is unnecessary in most settings. CONCLUSIONS:RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).

Introduction: IBS is a highly prevalent symptom-based condition with a heterogeneous pathophysiology. Increased prevalence of SIBO has been reported in IBS patients but clinical profiles of IBS patients with and without concurrent SIBO need further characterization. This study aims to determine whether demographics, gastrointestinal symptoms or disease-specific quality of life differ in patients with IBS-D with and without SIBO assessed by glucose HBT. Methods: Prospective, tertiary-care center, study of adults fulfilling Rome IV criteria for IBS-D. Patients with underlying GI (e.g. IBD) or systemic (e.g. scleroderma) disease that could explain IBS symptoms were excluded. Other exclusion criteria were: pregnancy, prior GI surgery, recent GI infection, use of antibiotics or probiotics. All patients graded their daily individual IBS symptoms for at least 2 weeks on an 11-point numerical rating scale questionnaire (e.g. 0-no pain, 10-max pain). Stool consistency was assessed with Bristol Stool Form Scale. Validated surveys including IBS-severity scoring system (IBS-SSS) and IBS-Quality of Life (IBS-QOL) were also completed. Home-based glucose HBT was completed by all participants per standardized protocol. Positive glucose HBT for SIBO was defined by ≥20 parts per million/ppm hydrogen (H2) rise over the baseline value within 90 mins post solution challenge and/or ≥10 ppm methane (CH4) at any time. Results: Fifty-six patients completed this ongoing study (mean age 44 yrs, 73% female, 91% White, mean BMI 30.1). The positivity rate for glucose HBTs was 43% (24/56). Demographic characteristics of patients with positive vs negative HBT were similar although patients with positive glucose HBT trended to be slightly younger and female. There were no statistically significant differences in average daily IBS individual symptoms scores, nor in daily stool frequency and consistency scores, between patients with positive vs negative HBT (Table 1). IBS-SSS scores also did not significantly differ between the groups. Similarly, average IBS-QOL total and subscale scores were similar between patients with positive vs negative glucose HBT. Conclusion: Amongst patients with Rome IV IBS-D, >40% will have a positive glucose HBT suggestive of SIBO. IBS-D patients with and without a positive HBT have similar demographics, severity of IBS symptoms and degree of IBS-specific quality of life impairment. This data suggests that clinical characteristics cannot distinguish between those with a positive or negative breath test. Table 1. - Symptoms severity and IBS-specific quality of life in IBS-D patients with positive and negative glucose hydrogen breath test Symptoms Positive Glucose HBT (n=24) Negative Glucose HBT (n=32) P-value Abdominal pain (mean) 5.36 5.31 0.45 Bloating (mean) 5.46 5.25 0.33 Urgency with Bowel Movements (mean) 5.27 5.34 0.45 Bowel Movements Frequency (N/day) 2.59 3.1 0.12 Bowel Movements Consistency (BSFS)* 5.46 5.24 0.18 Number of Days with Loose Bowel Movements / Week 4.96 4.57 0.21 Questionnaires IBS-SSS** 264 274.6 0.23 IBS-QOL (total score) 104.5 101.8 0.35 *BSFS: Bristol Stool Form Scale; **IBS-SSS: IBS-Severity Scoring System.