BACKGROUND Indoleamine 2,3 dioxygenase 1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn’s disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine. METHODS Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by physician’s global assessment. Serum tryptophan and kynurenine were measured by high pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks. RESULTS 25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. CONCLUSIONS IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity.

Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort.

Background Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT. Methods Forty previously-completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder. Results The total group agreement was moderate (κ = 0.57; 95% CI 0.56–0.59) for EPT and fair (κ = 0.32; 0.30–0.33) for CLT. Inter-rater agreement between attendings was good (κ = 0.68; 0.65–0.71) for EPT and moderate (κ = 0.46; 0.43–0.50) for CLT. Inter-rater agreement between fellows was moderate (κ = 0.48; 0.45–0.50) for EPT and poor to fair (κ = 0.20; 0.17–0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR 3.3; 95% CI 2.4–4.5; p<0.0001) and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than EPT (OR 3.4; 2.4–5.0; p<0.0001). Conclusions Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses was demonstrated with analysis using EPT over CLT among our selected raters. Based on these findings, EPT may be the preferred assessment modality of esophageal motility.

Background Irritable bowel syndrome (IBS) is a common abdominal pain disorder without an organic explanation. Abuse histories (physical, sexual, emotional) are prevalent in IBS. While abuse relates to mood disorders (depression and anxiety) also common in IBS, the influence of abuse on GI symptoms and health-related quality of life (HRQOL) and its independence from psychological symptom comorbidity, has not been studied. Methods Consecutive GI outpatients completed the ROME III Research Diagnostic Questionnaire and questionnaires on trauma (Life-Stress Questionnaire), mood (Beck Depression/Anxiety Inventories), somatic symptoms (PHQ-12) and HRQOL (SF-36). Current GI symptom Severity and Bother were assessed using 10-cm VAS scales. Key Results 272 ROME-defined IBS (47.6±0.9 yrs, 81% female) and 246 non-FGID (51.6±1.0 yrs, 65% female) subjects participated. IBS patients reported greater rates of physical, sexual, and emotional abuse (p < 0.006 each), and higher depression, anxiety, and somatic symptoms (p < 0.001). Greater bowel symptom bother (7.4±0.2 vs 6.7±0.2, p=0.040), severity (7.7±0.2 vs 6.5±0.2, p<0.001), recent symptomatic days (9.8±0.4 vs. 8.5±0.3, p=0.02), and poorer HRQOL (40.9±2.3 vs 55.5±1.7, p<0.001) were noted in IBS with abuse. Abuse effects were additive, with greater IBS symptom severity and poorer HRQOL noted in cases with multiple forms of abuse. Mediation analyses suggested that abuse effects on GI symptoms and HRQOL were partially mediated by mood. Conclusions & Inferences Abuse experiences common among IBS sufferers are associated with reports of greater GI symptoms and poorer HRQOL, particularly in those with multiple forms of abuse; this relationship may be partially mediated by concomitant mood disturbances.

Background Tricyclic antidepressants (TCAs) have efficacy in treating irritable bowel syndrome (IBS). Some clinicians use TCAs to treat residual symptoms in inflammatory bowel disease (IBD) patients already on decisive IBD therapy or with quiescent inflammation, although this strategy has not been formally studied. Goals The aim of this study was to examine the efficacy of TCA therapy in IBD patients with residual symptoms, despite controlled inflammation, in a retrospective cohort study. Study Inclusion required initiation of TCA for persistent gastrointestinal symptoms. IBD patients had inactive or mildly active disease with persistent symptoms despite adequate IBD therapy as determined by their physician. Symptom response was compared with IBS patients. Established Likert scales were used to score baseline symptom severity (0 = no symptoms, 3 =severe symptoms) and TCA response (0= no improvement; 3 = complete satisfaction). Results Eighty-one IBD [41.3 ± 1.7y, 56F; 58 Crohn's disease/23 ulcerative colitis (UC)] and 77 IBS (46.2 ± 1.7y, 60F) patients were initiated on a TCA therapy. Baseline symptom scores (IBD, 2.06 ± 0.03; IBS, 2.12 ± 0.04; P = 0.15) and symptom response to TCA therapy (IBD, 1.46 ± 0.09; IBS, 1.30 ± 0.09; P = 0.2) were similar in both the groups. At least moderate improvement (Likert score ≥ 2) on TCA was achieved by comparable proportions of patients (59.3% IBD vs. 46% IBS; P = 0.09). Within IBD, response was better with UC than Crohn's disease (1.86 ± 0.13 vs. 1.26 ± 0.11, respectively, P = 0.003). Conclusions In a clinical practice setting, TCA use led to moderate improvement of residual gastrointestinal symptoms in IBD patients for whom escalation of IBD therapy was not planned. UC patients demonstrated higher therapeutic success. IBD symptom responses were similar to IBS patients.