Short chain fatty acids (SCFA) are key microbial metabolites that modulate intestinal homeostasis and may influence irritable bowel syndrome (IBS) pathophysiology. We aimed to assess microbial features associated with SCFA and determine if features varied across IBS subtypes and endophenotypes. We analyzed stool microbial metagenomes, stool SCFA, and measurable IBS traits (stool bile acids, colonic transit, stool form) in 41 patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and 17 healthy controls. We used partial canonical correspondence analyses (pCCA), conditioned on transit, to quantify microbe-SCFA associations across groups. We further compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by their stool characteristics as well as stool microbiomes of patients with and without clinical bile acid malabsorption (BAM). Microbe-SCFA associations differed across groups and revealed key taxa including Dorea sp. CAG:317 and Bifidobacterium pseudocatenulatum in IBS-D and Akkermansia muciniphila and Prevotella copri in IBS-C that that could underlie subtype-specific microbially-mediated mechanisms. The greatest number of microbe-SCFA associations were observed in IBS-D. Several SCFA-producing species demonstrated inverse correlations with SCFA. Fewer bacterial taxa were associated with acetate to butyrate ratios in IBS compared to health. In participants selected by stool form, we demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D patients with BAM. Keystone taxa responsible for SCFA production differ by IBS subtype and traits. IBS microbiomes appear exhibit reduced functional redundancy. Differences in substrate preferences are also linked to bowel functions. Focusing on taxa that drive SCFA profiles and stool form may be a rational strategy for identifying relevant microbial targets in IBS.

Background Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications.Methods Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup.Results Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib.Conclusions The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care. Differing approaches to inflammatory bowel disease (IBD) and IBD-mimics directly impact the quality and cost of patient care. During a 5-year period at IBD LIVE, 17.5% of cases were IBD-mimics, many of which originally received advanced therapies for presumed IBD. Graphical Abstract

Abstract INTRODUCTION Since 2009, inflammatory bowel disease (IBD) specialists have been utilizing “IBD Live,” a weekly live video conference with a global audience of 150-200 participants, to discuss the multidisciplinary management of their commonly seen and most challenging cases. While most cases presented were confirmed as IBD, a substantial number were mimics for which IBD was not the ultimate diagnosis. We previously categorized all IBD Live cases and identified the frequency of “IBD mimics.” Here, we examine the use of biologic medications for these cases which ultimately were determined to be something other than IBD. METHODS Cases have been recorded and archived since May 2018. 371 total cases from May 2018 through February 2023 were reviewed spanning 186 hours. 65 of those cases were determined to be IBD mimics, defined as those with features of IBD that ultimately resulted in a non-IBD diagnosis. IBD mimics were analysed and categorized in terms of their biologic usage. RESULTS 25 of the 65 mimics (38.5%) were treated with biologics for presumed IBD. 14 were treated with one biologic, 5 with two biologics, and 6 with three or more biologics. The biologics used in the management of these IBD mimics included infliximab (n=21), vedolizumab (n=12), adalimumab (n=11), ustekinumab (n=6), and certolizumab (n=1). Of the 25 cases of biologic usage without definitive confirmation of IBD, 6 ended up with a diagnosis where biologics were an appropriate treatment for the mimic. These mimics included drug-induced colitis (n=3), Behcet’s disease (n=1), segmental colitis associated with diverticulosis (SCAD; n=1), and CTLA-4 haploinsufficiency with autoimmune infiltrates (CHAI; n=1). Several of the IBD mimics were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialled on tofacitinib (for Sweet’s syndrome, PIK3cd, and SCAD). There were 3 patients with confirmed IBD, in remission on a biologic, who subsequently had symptoms concerning for an IBD flare. In each of these cases, IBD was not the cause of their symptoms (e.g., cecal volvulus). There were 4 patients with confirmed IBD, in remission off biologics, who later developed symptoms suspicious for an IBD flare. Each of these cases was trialled on biologics to treat the supposed flare; however, symptoms were ultimately found to be due to an IBD mimic (e.g., eosinophilic esophagitis). 33 of the 65 IBD mimics were never treated with biologics. DISCUSSION In a 5-year period at IBD Live, 17.5% of cases (65 of 371) were found to be IBD mimics. 38.5% (25 of 65) of these were treated with biologics. The diverse presentation of signs and symptoms of IBD and IBD mimics requires reassessment of the biologic therapy in patients without response. Often the biologic needs to be optimized for IBD, but in some cases, the diagnosis of IBD will need to be called into question. Table 1 IBD mimics and biologics used Abbreviations BADAS = bowel-associated dermatosis-arthritis syndrome, BCL = B-cell lymphoma, CD = Crohn’s Disease, CHAI = CTLA-4 haploinsufficiency with autoimmune infiltrates, C-MUSE = cryptogenic multifocal ulcerous stenosing enteritis, CMV = cytomegalovirus, CVID = common variable immunodeficiency, EGPA = eosinophilic granulomatosis with polyangiitis, GABA = gamma-aminobutyric acid, IBD = inflammatory bowel disease, IMHMV = idiopathic myointimal hyperplasia of the mesenteric veins, PIK3cd = phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit delta, PNH = paroxysmal nocturnal hemoglobinuria, SCAD = segmental colitis associated with diverticulosis, STI = sexually transmitted infection, UC = Ulcerative Colitis. Image 1: Biologic usage in IBD mimics

ABSTRACT Background Identifying microbial targets in irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBI) is challenging due to the dynamic nature of microbiota-metabolite-host interactions. SCFA are key microbial metabolites that modulate intestinal homeostasis and may influence IBS pathophysiology. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features varied across IBS subtypes and endophenotypes. Among 96 participants who were screened, 71 completed the study. We conducted in-depth investigations of stool microbial metagenomes, stool SCFA, and measurable IBS traits (stool bile acids, colonic transit, stool form) in 41 patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and 17 healthy controls. We used partial canonical correspondence analyses (pCCA), conditioned on transit, to quantify microbe-SCFA associations across clinical groups. To explore relationships between microbially-derived SCFA and IBS traits, we compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by their stool characteristics as well as stool microbiomes of patients with and without clinical bile acid malabsorption. Results Overall stool microbiome composition and individual taxa abundances differed between clinical groups. Microbes-SCFA associations differed across groups and revealed key taxa including Dorea sp. CAG:317 and Bifidobacterium pseudocatenulatum in IBS-D and Akkermansia muciniphila and Prevotella copri in IBS-C that that may drive subtype-specific microbially-mediated mechanisms. Strongest microbe-SCFA associations were observed in IBS-D and several SCFA-producing species surprisingly demonstrated inverse correlations with SCFA. Fewer bacterial taxa were associated with acetate to butyrate ratios in IBS compared to health. In participants selected by stool form, we demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D patients with BAM. Conclusion Keystone taxa responsible for SCFA production differ according to IBS subtype and traits and the IBS microbiome is characterized by reduced functional redundancy. Differences in microbial substrate preferences are also linked to bowel functions. Focusing on taxa that drive SCFA profiles and stool form may be a rational strategy for identifying relevant microbial targets in IBS and other DGBI.

Introduction: Inflammatory bowel disease (IBD), specifically Crohn’s Disease (CD) and Ulcerative Colitis (UC), results in an increased risk of colorectal cancer. This risk increases with disease duration and severity and thus, those diagnosed in childhood are at high risk for dysplasia1. It has not been studied whether those diagnosed with IBD in childhood are being surveilled per guidelines. Our aim was to determine compliance in patients with pediatric onset IBD with guideline-recommended colonoscopy surveillance. Methods: This is a retrospective cohort study conducted using data obtained from patients in the Indiana University pediatric IBD patient registry. Individuals aged 10-30 years who were seen by a gastroenterologist between 1/2012-12/2021, had Crohn’s colitis involving more than 1/3 of their colon or UC proximal the rectum, and had ten years of follow-up were included. Patient demographics, age at diagnosis, disease severity, medication use and data around expected time of dysplasia screening were collected. Results: 37 participants were included in the study. Their mean age was 18.4+0.4, 27% were female, 5.4% were Black, and 5.4% Hispanic. The mean disease duration was 12.6+2.5 years, and 59.5% patients had CD. Only five subjects (13.5%) received the recommended dysplasia surveillance, and four of five had UC (P=0.047). Of those who did not get dysplasia surveillance, 20 had colonoscopies to evaluate disease activity and were not in remission. The remaining 12 patients did not have any colonoscopy done during the recommended time frame. Of those not in remission, 9/20 were not on a biologic or small molecule therapy despite not being in endoscopic remission. Only one patient was transitioned to adult care, but was not among the participants who received dysplasia screening. Conclusion: Despite the higher risk of dysplasia and colorectal cancer in this at risk population, most of those with pediatric onset IBD and cared for by pediatric gastroenterologists are not getting guideline recommended surveillance. The reasons for this are unclear, and needs to be further studied especially with the rise of early onset colorectal cancer to improve surveillance (Table 1). References: 1. Aardoom MA, Joosse ME, de Vries ACH, Levine A, de Ridder L. Malignancy and Mortality in Pediatric-onset Inflammatory Bowel Disease: A Systematic Review. Inflamm Bowel Dis 2018;24(4):732-741. Table 1. - Patient demographics and IBD type amongst pediatric patients eligible for dysplasia and cancer surveillance Dysplasia Screen Completed (n=5) No Dysplasia Screen (n=32) Total (n=37) P-value Mean (SD) Age 19.1 (1.2) 18.3 (2.8) 18.4 (2.7) 0.41 Mean (SD) Age at Diagnosis 6.4 (1.1) 5.7 (3.2) 5.7 (3.0) 0.35 Age at IBD Diagnosis, n (%) 0.59 ≤ 6 3 (60%) 21 (65.6%) 24 (64.9%) > 6 2 (40%) 11 (34.3%) 13 (35.1%) Mean (SD) Disease Duration 12.7 (0.9) 12.6 (2.7) 12.6 (2.5) 0.52 Sex: female, n (%) 0 (0%) 10 (31.2%) 10 (27%) 0.16 Ethnicity: Hispanic, n (%) 0 (0%) 2 (6.2%) 2 (5.4%) 0.90 Race, n (%) 0.77* Black 0 (0%) 2 (6.2%) 2 (5.4%) White 5 (100%) 28 (87.5%) 33 (89.2%) Asian 0 (0%) 2 (6.2%) 2 (5.4%) Insurance, n (%) 0.24 Medicaid 0 (0%) 8 (25%) 8 (21.6%) Commercial 5 (100%) 24 (75%) 29 (78.4%) IBD Type, n (%) 0.047** Ulcerative Colitis 4 (80%) 10 (31.2%) 14 (37.8%) Crohn’s Disease 1 (20%) 21 (65.6%) 22 (59.5%) IBD-Unclassified 0 (0%) 1 (3.1%) 1 (2.7%) *Barnard’s exact test comparing Black vs. White ** Barnard’s exact test comparing UC vs. CD.

BACKGROUND Indiana State opioid prescription legislation has been shown to decrease overall opioid prescriptions. However, this effect has not been studied in specific diseases associated with chronic pain such as inflammatory bowel disease (IBD). We aimed to determine the effect of state opioid prescription legislation on opioid prescribing patterns in IBD. METHODS A retrospective cohort analysis using an interrupted time-series from December 15, 2010 to July 1, 2018, with 2 time periods separated by Title 844 of the Indiana Administrative Code, in a statewide health care system capturing the majority of the state's population including all adult patients with IBD. The primary outcome was opioid prescription rate per person-year. RESULTS In total, 9436 patients met inclusion criteria. After legislation, the total number of opioid orders per patient-year continued to increase (0.543, 95% CI, 0.528-0.558, to 0.663, 95% CI, 0.654-0.672), with fewer scripts from the emergency department (0.113, 95% CI, 0.106-0.120, to 0.092, 95% CI, 0.088-0.095) and more from outpatient providers (0.303, 95% CI, 0.292-0.314 to 0.432, 95% CI, 0.424-0.439). There were increases in biologic (0.206, 95% CI, 0.197-0.215 to 0.517, 95% CI, 0.509-0.525) and steroid (0.182, 95% CI, 0.173-0.190 to 0.237, 95% CI, 0.232-0.243) prescriptions per person-year following legislation. Factors associated with heavy opioid use included chronic steroids (odds ratio, 5.030; 95% CI, 4.176-6.054), history of IBD-related surgery (odds ratio, 2.807; 95% CI, 2.367-3.323) and current smoking (odds ratio, 2.650; 95% CI, 2.223-3.158). CONCLUSIONS Despite legislation and the increased use of disease-modifying drugs, statewide opioid prescriptions continued to increase. The increase in opiate use, high steroid use, and significant health care utilization suggests poor underlying disease control.

Introduction: Since 2009, a group of inflammatory bowel disease (IBD) specialists have been utilizing “IBD Live,” a weekly live video conference with a global audience of 150-200 participants, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed as IBD, a substantial number were mimics for which IBD was not the ultimate diagnosis. We have prospectively categorized all IBD Live cases and identified “IBD mimics” with consequent clinical management implications. Methods: Cases have been recorded and archived since May 2018. 371 total cases from May 2018 through February 2023 were reviewed spanning 186 hours. IBD mimics were defined as those cases with features of IBD that ultimately resulted in a non-IBD diagnosis. IBD mimics were analysed and categorized by original suspected diagnosis, diagnostic workup, and the evaluation that led to the correct diagnosis. Results: 306 of the 371 cases discussed were IBD including 193 Crohn’s disease (CD), 107 ulcerative colitis (UC) and 6 IBD-unclassified (IBD-U). 65 (17.5%) cases (Table 1) were mimics with a presumed initial diagnosis of IBD. The evaluations that ultimately resulted in the correct diagnosis included: additional endoscopic biopsies (n=13, 21%), surgical exploration/pathology (n=10, 16.5%), biopsies from outside the GI tract (n=10, 16.5%), genetic and other laboratory testing (n=8, 13%), deeper analysis of patient history, including medication review, family, social, and sexual history (n=8, 13%), imaging (n=5, 8%), balloon enteroscopy (n=5, 8%), and capsule endoscopy (n=2, 3%). We further delineated the diagnostic testing into three categories that ultimately yielded a correct diagnosis: 1) procurement of additional tissue for evaluation, 2) different radiographic or endoscopic evaluation from the original work-up, especially inspection of the small bowel, and 3) more thorough history-taking. Conclusion: In a 5-year period at IBD Live, 17.5% of cases were found to be IBD mimics, many of which originally received advanced therapies for presumed CD or UC. The diverse presentation of IBD cases and the complexity of both assessment and diagnosis necessitates significant consideration of IBD mimics at all times. The substantial differences and often conflicting treatment approaches to IBD vs IBD mimics will directly impact the quality and cost of patient care. Table 1. - IBD mimics presented at IBD live, 2018-2023 Category Mimic N = Diagnosis Systemic diseases CD 21 Vasculitis (7), CVID (2), Sweets (1), EGPA (1), CHAI (1), BADAS (1), Behcet’s (1), eosinophilic esophagitis (1), carcinoid (1), histoplasmosis (1), sarcoidosis (1), amyloidosis (1), PIK3cd (1), adrenal insufficiency (1) Ileal disorders CD 16 BCL (4), IMHMV (2), SCAD (2), follicular lymphoma (1), T-cell lymphoma (1), Kaposi’s sarcoma (1), Meckel’s diverticulum (1), appendiceal carcinoid (1), tropical sprue (1), collagenous sprue (1), autoimmune enteropathy (1) Medication induced UC/CD 8 Immune checkpoint inhibitor (Pembrolizumab [1], Ipilimumab + Nivolumab [2]), chemotherapy (Encorafenib + Binimetinib [1]), Olmesartan (1), Mycophenolate (1), mu-opioid receptor agonist (Kratom [1]), GABA-mimetic (Phenibut [1]) Colonic inflammation UC 5 Ischemic colitis (1), pouchitis (1), diversion colitis (1), CMV colitis (1), STI proctitis (1) Polyposis disorders UC 2 Cronkhite Canada syndrome (1), juvenile polyposis syndrome (1) Obstruction CD 2 Abdominal actinomyces (1), cecal volvulus (1) Peri-anal disease CD 1 Cryptoglandular abscess (1) No diagnosis made UC/CD 11 Unclear at time of IBD Live (9), presumed C-MUSE (1), presumed congenital tailgut cyst (1) Abbreviations: BADAS – bowel-associated dermatosis-arthritis syndrome; BCL – B-cell lymphoma; CHAI – CTLA4 haploinsufficiency with autoimmune infiltrates; C-MUSE – cryptogenic multifocal ulcerous stenosing enteritis; CMV – cytomegalovirus; CVID – common variable immunodeficiency; EGPA – eosinophilic granulomatosis with polyangiitis; IMHMV - idiopathic myointimal hyperplasia of mesenteric veins; SCAD – segmental colitis associated with diverticulitis; STI – sexually transmitted infection; TB – tuberculosis.

Background Small Intestinal Bacterial Overgrowth (SIBO) is a heterogenous syndrome from excessive bacteria in the small intestine lumen. It is unknown if differences in type of bacterial overgrowth lead to differences in symptoms. Methods Patients with suspected SIBO were recruited prospectively. Exclusion criteria were probiotics, antibiotics, or bowel prep in preceding 30 days. Clinical characteristics, risk factors, and labs were collected. Proximal jejunal aspiration via upper enteroscopy was performed. Aerodigestive tract (ADT) SIBO was defined as > 10 5 CFU/mL of oropharyngeal and respiratory bacteria. Colonic-type SIBO was defined as > 10 4 CFU/mL of distal small bowel and colon bacteria. Aims were to compare symptom profiles, clinical complications, labs, and underlying risk factors between ADT and colonic-type SIBO. Key Results We consented 166 subjects. Aspiration was not obtained in 22 and SIBO was found in 69 (49%) of 144 subjects. Daily abdominal distention trended towards more prevalent in ADT SIBO versus colonic-type SIBO (65.2% vs 39.1%, p = 0.09). Patient symptom scores were similar. Iron deficiency was more prevalent in ADT SIBO (33.3% vs 10.3%, p = 0.04). Subjects with colonic-type SIBO were more likely to have a risk factor for colonic bacteria colonization (60.9% vs 17.4%, p = 0.0006). Subjects with ADT SIBO were more likely to have a risk factor for diminished gastric acid (91.3% vs 67.4%, p = 0.02). Conclusions & Inferences: We found differences in iron deficiency and underlying risk factors between ADT and colonic-type SIBO. However, distinct clinical profiles remained elusive. Future research is needed to develop validated symptom assessment tools and distinguish cause from correlation.

Abstract INTRODUCTION Celiac disease (CeD) and inflammatory bowel disease (IBD) are autoimmune diseases of the bowel with similar clinical symptoms. This study aims to characterize the clinical course of both diseases in subjects with overlap of CeD and IBD (CeD+IBD) on a gluten free diet (GFD) and IBD medications. METHODS We conducted a retrospective study of demographic and serological characteristics in subjects with CeD+ IBD at a large academic center using appropriate International Classification of Disease (ICD)-10 codes from 2017 to June 2022. RESULTS 36 subjects had IBD +CeD. 96% of subjects were Caucasian and 67% were female. The diagnosis of CeD post-dated the diagnosis of IBD by 3.6 years. Ulcerative colitis (UC) and Crohn’s disease (CD) occurred equally in IBD +CeD. About 75% of subjects had L2+L3, B1 phenotype per Montreal classification. 44% of UC +CeD subjects had pancolitis with 72% of them being classified as S0 (never severe) per Paris classification. 83% of subjects initiated a self-taught GFD. Only 17% of subjects sough advice from a celiac dietician. Mean duration at which GFD was initiated was 0.7 yrs from the initial diagnosis of CeD. Only 1/36 subjects followed a strict GFD during 6.5 years of follow up. The second and third assessment of GFD happened after a mean of 3.7 yrs and 5.2 yrs from the time of initiation of a GFD with only 1/36 subjects adhering to a strict GFD at these time points. Serum tTG IgA levels were tested on average at 4, 91, 154, 186 and 192 weeks from the diagnosis of CeD, with a consistent drop in mean tTG IgA titers to 45, 33, 19, 25 and 4 respectively. Only 1 subject got tTG IgA measurements over the next 250 weeks of follow up. Over a 10.1 year follow up since the diagnosis of IBD, descending proportions of subjects needing IBD medications were as follows: topical 5-ASA (aminosalicyates) (19/36)>oral steroids (18/36)> anti-TNF (tumor necrosis factor) (18/36)> anti-integrins (12/36)> azathioprine (10/36)> anti-IL12/23 (8/36)> topical 5-ASA (4/36)> MTX (methotrexate) (5/36)> topical steroids at 2/36. Mean time to initiation of IBD medications (in weeks) after GFD initiation as a reference point were in an order of oral 5-ASA (-67) < anti-TNF (-39) < AZA (-14) CONCLUSIONS Majority of subjects depended on a self-educated GFD. A small proportion of CeD +IBD subjects were assessed per clinical guidelines with respect to adherence to a GFD, serology. At least 50% of subjects with CeD+IBD needed escalation of IBD treatment to biologics and/or steroid rescue over 10 years despite initiation of GFD (albeit suboptimal). We need to further substantiate these findings with exclusive IBD and celiac control groups. We suggest establishing CeD centers at tertiary hospitals for adequate clinical guideline adherence.

Introduction: A small portion of Inflammatory bowel disease (IBD) subjects have celiac disease (CeD). We conducted a retrospective case-control study to compare disease characteristics of subjects with IBD+ CeD vs CeD. Methods: Patients were screened from January 2017 until June 2022 using appropriate ICD-10 codes for IBD and CeD. Data was collected including demographics, gluten-free diet (GFD) adherence patterns, celiac disease symptom index (CSI), serologic and histologic remission of CeD, from earliest available until time of administrative censoring. Results: 80 subjects with CeD and 36 subjects with IBD+ CeD were included. 70% of CeD and 64% of IBD+ CeD subjects were female (P=0.54). The median age at diagnosis of CeD in the CeD and IBD+ CeD subjects was similar. There was a higher rate of self-taught (83%), internet-taught (14%), or book-taught (14%) initiation of GFD in the IBD+ CeD group as compared to 50%, 0%, and 1% respectively in the CeD group (all p£0.01). Dietician referral was low in both groups (< 22%). The prevalence of the following components of the CSI were more frequently reported in IBD+ CeD: abdominal pain (89%), nausea and vomiting (58%), bloating (58%), diarrhea (89%), and weight loss (78%) when compared to 53%, 29%, 29%, 48%, and 13% in CeD, respectively (all p£0.01). Other significant co-morbidities that were notably more common in IBD+ CeD include unexplained anemia (47%), malnutrition (19%), arthritis (8%), and rheumatoid arthritis (RA) (8%) when compared to CeD group at 21%, 1%, 4%, 0%, respectively (P< 0.05). The median and IQR serum tTG IgA titers dropped consistently over a 5-year timeline in both groups (Figure 1a). Kaplan-Meir (KM) curves indicated a similar estimated survival probability by log rank test of Marsh Score remaining 1 or below at 2 years in the IBD+ CeD group when compared to CeD group (Figure 1b) (P=0.37) over the observed period of years since first GFD start date. No subjects with IBD+ CeD had follow-up duodenal biopsies beyond 2 years. Conclusion: Only 20% of IBD+ CeD were referred to a dietician for initiation of a GFD. Further, CSI burden and associated co-morbid conditions were higher in IBD+ CeD group. Very few IBD+ CeD underwent duodenal biopsy beyond 2 years and celiac serologies beyond 5 years. This study highlights the need for clinicians to objectively assess celiac disease activity and GFD adherence, especially in IBD+ CeD with high CSI symptom burden (see Table 1).Figure 1.: (A) Comparison of serum tTG IgA titers between CeD and IBD+ CeD over the course of follow up. (B) Kaplan-Meir curve demonstrating the estimated survival probability by log rank testing of Marsh score remaining 1 or below in CeD and IBD+ CeD. Table 1. - Comparison of CeD Baseline Characteristics between CeD+IBD and CeD Variable CeD (N=80) CeD+IBD (N=36) P-value Female 55 (69.6%) 23 (63.9%) 0.542 Age at CeD diagnosis median (IQR) 36.0 (22.0, 45.0) 25.5 (19.0, 54.5) 0.664 Duration of CeD median (IQR) 6.2 (3.5, 9.2) 5.1 (2.1, 7.9) 0.228 Age at end of study median (IQR) 41.1 (29.5, 51.6) 34.1 (26.2, 58.3) 0.433 Duration of GFD median (IQR) 6.1 (2.9, 9.2) 5.2 (2.5, 7.0) 0.352 Mechanism of GFD Education, n (%) Self-taught 40 (50.0%) 30 (83.3%) < 0.001 Internet 0 (0%) 5 (13.9%) 0.002 Book 1 (1.3%) 5 (13.9%) 0.011 Dietician 17 (21.3%) 6 (16.7%) 0.567 Celiac Dietician 0 (0%) 0 (0%) Other 18 (22.5%) 3 (8.3%) 0.067 CeD Symptoms Present, n (%) Unexplained anemia 17 (21.3%) 17 (47.2%) 0.004 IgA Deficiency 1 (1.3%) 0 (0%) 1.000 Malnutrition 1 (1.3%) 7 (19.4%) 0.001 Abdominal Pain 42 (52.5%) 32 (88.9%) < 0.001 Nausea/vomiting 23 (28.8%) 21 (58.3%) 0.002 Bloating 23 (28.8%) 21 (58.3%) 0.002 Constipation 18 (22.5%) 8 (22.2%) 0.974 Diarrhea 38 (47.5%) 32 (88.9%) < 0.001 Weight loss 10 (12.5%) 28 (77.8%) < 0.001 Weight gain 10 (12.5%) 3 (8.3%) 0.752 Arthritis 4 (5.0%) 8 (22.2%) 0.008 Fibromyalgia 2 (2.5%) 4 (11.1%) 0.074 Rheumatoid Arthritis 0 (0%) 3 (8.3%) 0.028 Thyroiditis 7 (8.8%) 6 (16.7%) 0.220 Type 1 DM 6 (7.5%) 1 (2.8%) 0.433

INTRODUCTION: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. METHODS: We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. RESULTS: Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [−0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). DISCUSSION: Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.

Introduction: Intestinal strictures affect one-third of individuals with Crohn’s disease (CD) within ten years of disease onset. Endoscopic balloon dilation (EBD) is a minimally invasive procedure for managing fibrostenotic strictures in patients with CD. Long-term outcomes after EBD are poorly defined in the literature. The aims of this study are to evaluate the efficacy of EBD in delaying surgery for the treatment of strictures in patients with CD and identify clinical, endoscopic, and stricture-related factors associated with avoidance of surgery after five years of EBD. Methods: Retrospective cohort study including all patients with CD undergoing EBD at a tertiary academic center between 01/2007-12/2021. Data for demographics, disease characteristics, stricture characteristics, surgical history, medication history, need for surgical intervention, time to surgical intervention, and need for re-dilation were collected. Patient outcomes were followed from their index dilation up to five years post dilation. Results: 378 patients with CD diagnosis (51% female) with a mean age 45 years underwent EBD during the study period (681 total dilations). The location of the stricture was upper gastrointestinal in 30 patients (9%), ileal (35%), colonic (13%), ileocolonic (44%) in other patients. Among these patients, 118 (31%) required surgery for CD-related stricture during the five-year follow-up periods. Prednisone therapy was a predictor for progression to surgery post-EBD (P=0.002). 156 patients (43%) required re-dilation. Patients with De Novo strictures were more likely to undergo surgery compared to those with anastomotic strictures (P=0.034). Eight patients (2%) had complications with three of those requiring surgery. Conclusion: This is one of the largest single-center studies looking at outcomes of EBD for treatment of CD-related strictures. 69% of patients treated with EBD avoided surgery within a five-year follow-up period. Steroid therapy was predictive of surgical resection within five years. Similar to current literature, anastomotic strictures had better outcomes than De Novo. Larger prospective studies are needed to confirm our results (Table 1). Table 1. - Patient characteristics, Montreal classification at time of dilation, steroid use, stricture characteristics, and response to endoscopic dilation All Patients (n=378) Surgery post-dilation (n=118) No surgery post-dilation (n=260) P-value Female, n(%) 194 (51%) 68 (58%) 126 (49%) 0.098 Race, n(%) 0.100 White 356 (94%) 112 (95%) 244 (94%) Black 17 (5%) 4 (3%) 13 (5%) Age at dilation (years), mean (sd) 30 (16) 31 (16) 29 (15) 0.158 BMI, mean (sd) 27 (7) 27 (6) 27 (7) 0.935 Age at Diagnosis 0.469 A1 (< 16 years) 70 (21%) 20 (18%) 59 (23%) A2 (17-40 years) 205 (56%) 67 (59%) 134 (54%) A3 ( >40 years) 84 (23%) 27 (24%) 57 (22%) Behavior of Disease, n(%) 0.013 Stricturing 269 (72%) 72 (61%) 197 (77%) Stricturing and Penetrating 105 (28%) 46 (39%) 59 (23%) Location, n(%) 0.228 L1 (Ileal) 131 (35%) 47 (40%) 84 (33%) L2 (Colonic) 50 (13%) 11 (9%) 39 (15%) L3 (Ileocolonic) 163 (44%) 52 (44%) 111 (43%) L4 (Upper GI) 30 (9%) 8 (7%) 22 (8%) Perianal Disease, n(%) 109 (29%) 43 (36%) 66 (25%) Prednisone at dilation, n(%) 60 (16%) 29 (25%) 31 (12%) 0.002 Endoscopic Severity at time dilation, n(%) 0.256 Remission 51 (14%) 12 (11%) 39 (15%) Mild 119 (32%) 34 (30%) 85 (23%) Moderate 119 (32%) 35 (31%) 84 (23%) Severe 83 (22%) 32 (28%) 51 (20%) Location of Stricture, n(%) 0.255 Ileum 105 (28%) 42 (46%) 63 (25%) Ileocolonic 174 (46%) 46 (39%) 128 (50%) Colonic 43 (11%) 12 (10%) 31 (12%) Upper GI 24 (6%) 7 (6%) 17 (7%) Jejunal 7 (2%) 3 (3%) 4 (2%) Anal 22 (6%) 8 (7%) 14 (5%) Stricture type, n(%) 0.034 De Novo 214 (57%) 76 (65%) 138 (53%) Anastomotic 162 (43%) 41 (35%) 121 (47%) Need for redilation, n(%) 156 (43%) 49 (42%) 107 (43%) 0.847

Introduction: There are limited studies to elucidate the potential benefit of minimally invasive interventions such as endoscopic balloon dilation (EBD) for the treatment of Upper Gastrointestinal Crohn’s Disease-related strictures. The aim of this study is to evaluate the safety and efficacy of EBD in delaying or preventing surgery in patients with upper GI (UGI) Crohn’s disease (CD). Methods: This is a retrospective cohort study including all patients with UGI CD undergoing EBD at a tertiary academic center between 01/2007 and 12/2021. Data for demographics, disease characteristics, stricture characteristics, surgical history, medication history, need for surgical intervention, time to surgical intervention, and need for re-dilation were collected. Patient outcomes were followed from their index dilation up to 5 years post dilation. Results: 24 CD patients with UGI strictures (50% female) with a mean age of 41 years underwent EBD during the study period (26 distinct strictures with 47 total dilations). Locations of strictures were gastric (10), duodenal (9), gastroduodenal (3) and jejunal in 4 patients. Mean duration from CD diagnosis to first stricture dilation is 11 years. Mean age at diagnosis was 25 years old. Among these patients, 8/24 (33%) required surgery for CD-related stricture during the 5-year follow-up period. 12/26 strictures (46%) required re-dilation. Technical success was achieved in 88% of cases. The mean time to re-dilation and mean time to stricture-related surgery after first dilation was 357 days and 109 days, respectively. One patient had a mild complication post-dilation. 40% of gastric strictures required surgical resection compared to 11% of duodenal strictures and 25% of jejunal strictures (Table 1). Conclusion: Dilation of strictures in patients with UGI CD has a high rate of technical success, with minimal complication rate. Almost a third of patients required surgery. Gastric strictures were more likely to require surgery compared to duodenal strictures. Table 1. - Patients and characteristics All Patients (n=24) Surgery post-dilation (n=8) No surgery post-dilation (n=16) P-value Female, n (%) 12 (50%) 4 (50%) 8 (50%) 1.0000 Age at dilation (years), mean (std) 41.47 (19.79) 37.6 (25.07) 43.08 (18.20) 0.6186 BMI, mean (std) 24.21 (4.91) 21.50 (4.06) 25.56 (4.84) 0.0538 Smoking Status, n (%) 0.3676 Current 2 (8%) 0 2 (13%) Never 20 (83%) 8 (100%) 12 (75%) Past 2 (8%) 0 2 (13%) Age at Diagnosis 0.8333 A1 (< 16 years) 5 (26%) 2 (28%) 3 (25%) A2 (17-40 years) 9 (47%) 4 (57%) 5 (42%) A3 ( >40 years) 5 (26%) 1 (14%) 4 (33%) Behavior of Disease, n (%) 0.6177 Stricturing 17 (81%) 6 (75%) 11 (85%) Stricturing and Penetrating 4 (19%) 2 (25%) 2 (15%) Prednisone at dilation, n (%) 5 (20.83%) 1 (12.5%) 4 (25.00%) 0.6311 Endoscopic Severity at time dilation, n (%) 0.3627 Remission 2 (8%) 1 (12.5)% 1 (6%) Mild 5 (21%) 0 5 (31%) Moderate 9 (38%) 4 (50%) 5 (31%) Severe 8 (33%) 3 (37.%) 5 (31%) Stricture type, n (%) 1.0000 De Novo 21 (91%) 7 (100%) 14 (88%) Anastomotic 2 (9%) 0 2 (12%) Need for redilation, n (%) 11 (45.83%) 4 (50.00%) 7 (43.75%) 1.0000 Location of stricture, n (%) Gastric 10 (38%) 6 (40%) 4 (60%) Duodenal 9 (35%) 1 (11%) 8 (89%) Gastroduodenal 3 (12%) 1 (33%) 3 (67%) Jejunal 4 (15%) 1 (25%) 3 (75%)

Introduction: Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions that affects over one million Americans. While biologic therapies have improved outcomes for patients with IBD as a whole, there is conflicting data on if obesity is an independent factor on the effectiveness of biologic therapy in IBD12. Our aim was to see if BMI, as a surrogate for obesity, was associated with higher healthcare utilization following the initiation of biologic therapy. Methods: Retrospective cohort study between 12/15/10-7/1/17 of subjects diagnosed with IBD patients based on ICD9-10 codes, on biologics, with at least >1 year of follow-up using the validated Indiana Network for Patient Care research database. Logistic regression was used to calculate odds ratios for ED visits, hospitalizations, surgery, steroids, and opioids for the year following initiation of biologic therapy. Results: 1,838 patients were included. Mean age was 47.0 (+18.8). Obese individuals were more likely to be female (59.1% vs. 52.9%; P< 0.001), Black (8.9% vs. 6.3%; P< 0.001), and non-smokers (49.2% vs. 40.3%; P< 0.001). Logistic regression models found those with a BMI >30, compared to those with BMI < 30, had higher odds of ED visits (OR 1.48 95% CI [1.09-2.00]; P=0.01) and opioid orders (OR 1.54 95% CI [1.23-1.92]; P=0.0001). Rates of hospital visits, IBD surgeries, and steroid orders did not significantly differ. Conclusion: A BMI >30 was associated with marginally higher odds of ED visits and opioid orders with no differences found for other outcomes. Our findings add to evidence from prior studies showing that obesity is possibly linked to inferior outcomes in patients with IBD on biologics.

Introduction: The incidence of inflammatory bowel disease (IBD) in the elderly is increasing as our population ages. The elderly population tends to suffer a more severe initial flare, though biologics are less often used in the elderly due to poorer response rates and more side effects1. Introducing biologics soon after initial diagnosis improves efficacy, yet the elderly are often excluded from randomized control trials for biologics, highlighting the need for more data in this vulnerable population. Our aims were to characterize biologic use for IBD in the elderly population (age >65) and assess healthcare utilization for elderly patients after starting biologics. Methods: Retrospective cohort study of IBD patients based on ICD9-10 codes, diagnosed between 12/15/10-7/1/17 with >1 year of follow-up using the Indiana Network for Patient Care research database. Age groups were created to evaluate trends in biologic use and outcome by age. Logistic regression was used to calculate odds ratios for ED visits, hospitalizations, IBD surgeries, steroids, and opioids for the year following initiation of biologic therapy. Results: 10,627 subjects were included. 55.4% were female, 89.7% were White, and 54.2% had Ulcerative Colitis. 1,606 were prescribed biologics with lower rates in the elderly (6.1% vs. 19.2%; P< 0.001). In logistic regression models, individuals age >65 had a significantly lower odds of having ED visits compared to those less than age 65 (OR 0.44 95% CI [0.19-0.87]; P=0.03) (Table 1). Hospital visits, IBD surgeries, steroid orders, and opioid orders did not significantly differ between ages >65 and < 65. Conclusion: Among those on biologics, those age >65 had lower odds of ED visits without significant differences in other healthcare utilization for the year following initiation of a biologic. These findings provide reassurance for the use of biologic therapy in elderly patients with IBD. References: 1. Juneja M, Baidoo L, Schwartz MB, Barrie A, 3rd, Regueiro M, Dunn M, et al. Geriatric inflammatory bowel disease: phenotypic presentation, treatment patterns, nutritional status, outcomes, and comorbidity. Dig Dis Sci. 2012;57(9):2408-15. Table 1. - Demographics and healthcare utilization outcomes of participants grouped by age<65 and 65+ Age < 65 (n=8369) Age ≥65 (n=2258) Total (n=10627) Female, n (%) 4633 (55.4%) 1252 (55.4%) 5885 (55.4%) Race, n (%) Black 652 (7.8%) 91 (4.0%) 743 (7.0%) White 7413 (88.6) 2119 (93.8%) 9532 (89.7%) Other 304 (3.6%) 48 (2.1%) 352 (3.3%) IBD Type, n (%) Ulcerative Colitis 2708 (32.4%) 1083 (48.0%) 3791 (35.7%) Crohn’s Disease 4732 (56.5%) 1023 (45.3%) 5755 (54.2%) IBD-Unclassified 929 (11.1%) 152 (6.7%) 1081 (10.2%) Immunomodulator, n (%) 1455 (17.4%) 294 (13.0%) 1749 (16.5%) BMI >30, n (%) 2920 (34.9%) 811 (35.9%) 3731 (35.1%) Smoking Status, n (%) Never 3675 (43.9%) 803 (35.6%) 4478 (42.1%) Former 850 (10.1%) 539 (23.9%) 1389 (13.1%) Current 1345 (16.1%) 158 (7.0%) 1503 (14.1%) Unknown 3257 (38.9%) 758 (33.6%) 3257 (30.6%) Prior ED Visit, n (%) 658 (7.9%) 132 (5.8%) 790 (7.4%) Prior Hospitalization, n (%) 530 (6.3%) 162 (7.2%) 692 (6.5%) Prior IBD Surgery, n (%) 179 (2.1%) 36 (1.6%) 215 (2.0%) Prior Steroids, n (%) 303 (3.6%) 58 (2.6%) 361 (3.4%) Prior Opioids, n (%) 568 (6.8%) 135 (6.0%) 703 (6.6%) ED Visit, OR [95% CI] (Age ≥65 vs < 65) -- -- 0.44 [0.19-0.87] Hospitalization, OR [95% CI] (Age ≥65 vs < 65) -- -- 1.35 [0.92-1.96] IBD Surgery, OR [95% CI] (Age ≥65 vs < 65) -- -- 1.17 [0.64-2.00] Steroids, OR [95% CI] (Age ≥65 vs < 65) -- -- 0.91 [0.59-1.37] Opioids, OR [95% CI] (Age ≥65 vs < 65) -- -- 0.73 [0.47-1.10]

Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. Patients 18–75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. Among 34 patients, 23 (68