Surgery for Crohn's Disease Is Associated with a Dysbiotic Microbiome and Metabolome: Results from Two Prospective Cohorts.

BACKGROUND AND AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, E lenta, A equalofaciens and G pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In two different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria as well as secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.

ExpLOring the role of the intestinal MiCrobiome in InflammATory bowel disease-AssocIated SpONdylarthritis (LOCATION-IBD).

Background: Inflammatory Bowel Disease (IBD)-associated arthritis is a frequent and potentially debilitating complication of IBD, that can affect those with or without active intestinal disease, and is often difficult to treat. The microbiome is known to play a role in IBD development and has been shown to be associated with inflammatory arthritis without concomitant IBD, but its role in IBD-associated arthritis is still unexplored. Further, disease localization is associated with development of IBD-associated arthritis, and stool compositional profiles are predictive of disease localization, yet mucosal location-specific microbiomes have not been well characterized. To address this gap in understanding, we designed a study (LOCATION-IBD) to characterize the mucosa-associated intestinal microbiome and metabolome in IBD-associated arthritis. Methods: Adults with an established diagnosis of IBD undergoing clinical colonoscopy between May of 2021 and February of 2023 were invited to participate in this study; those interested in participation who met inclusion criteria were enrolled. Prior to enrollment, participants were stratified into those with or without IBD-associated arthritis. All participants were interviewed and had clinical and demographic data collected, and 97.8% completed clinical colonoscopy with biopsy collection. Results and conclusion: A total of 182 participants, 53 with confirmed IBD-associated arthritis, were enrolled in this study, resulting in 1151 biopsies obtained for microbiome and metabolome analysis (median 6, mean 6.3 per participant). Clinical and demographic data obtained from the study population will be analyzed with microbiome and metabolome data obtained from biopsies, with the goal of better understanding the mechanisms underpinning the host-microbiome relationship associated the development of IBD-associated arthritis.

The Sigmoid Colon as an Unusual Primary Site of T Cell Lymphoma in a Patient Presenting With Brain Metastasis.

Intestinal T-cell lymphomas are an uncommon type of gastrointestinal malignancy, primarily found in the stomach and small bowel. The liver represents the most common distant organ for metastasis in gastrointestinal malignancies, followed by the lungs. Brain and muscular metastases are rare. We present intestinal T-cell lymphoma with a primary site in the sigmoid colon and metastasis to the brain, meninges, and psoas muscle. Biopsy of the malignant mass confirmed intestinal T-cell lymphoma. To our knowledge, this is the first colon T-cell lymphoma with primary brain and meningeal metastasis with another uncommon site of muscular metastasis.

Small bowel disease prevalence on video capsule endoscopy in chronic granulomatous disease-associated inflammatory bowel disease.

BACKGROUND AND AIM: Patients with chronic granulomatous disease (CGD) may develop inflammatory bowel disease (IBD). Characterization of small bowel disease in this cohort is scarce. Here, we sought to determine the prevalence and characteristics of small bowel disease and evaluate the clinical utility of video capsule endoscopy (VCE) for its diagnosis. METHODS: A retrospective study was performed on patients with CGD who were evaluated for gastrointestinal disease with VCE as a part of ongoing natural history studies at a single academic center. VCEs were reviewed for inflammatory findings and severity of disease utilizing the Capsule Endoscopy Crohn's Disease Activity Index. Radiographic studies and endoscopies performed within 30 days of VCE were compared with small bowel inflammatory findings. RESULTS: Twenty-six VCEs corresponding to 25 patients were found. The majority of patients were male and White; mean age was 28 years old. The majority (85%) demonstrated presence of small bowel inflammatory findings on VCE including strictures, ulcers, erosions, and erythema. Duodenal and ileal inflammatory disease on endoscopy did not correlate with disease on VCE. Moderate-severe colonic disease correlated with moderate-severe disease on VCE. Radiography did not correlate with disease on VCE. Prolonged small bowel transit time correlated with moderate-severe small bowel disease. CONCLUSIONS: Small bowel IBD was highly prevalent in this cohort of patients with CGD. Limitations included small sample size. Given that radiology and duodenal/ileal disease did not correlate with VCE findings, VCE-driven investigation of small bowel disease should be considered in patients with CGD-associated IBD, particularly those with colonic disease.

A Crohn's Disease Patient Found to Have Entamoeba histolytica Infection Causing Pyogenic Liver Abscess.

Entamoeba histolytica is a parasite that typically causes amoebic dysentery but can result in complications such as pyogenic liver abscess. Patients with inflammatory bowel disease often take immunosuppressive therapies that make them more susceptible to such infections. Notably, parasitic infections in this context are rare in nonendemic areas. We describe a 57-year-old man who recently started infliximab therapy for Crohn's disease and presented with fever and right upper quadrant pain. While hospitalized, this patient was diagnosed with Entamoeba histolytica liver abscess. This case demonstrates that parasitic infections should be considered early in immunocompromised patients with inflammatory bowel disease.

Patients with inflammatory bowel disease are more hesitant about Coronavirus disease 2019 vaccination.

Despite the impact of the Coronavirus Disease 2019 (COVID-19) pandemic, vaccine hesitancy remains common in the general public and patients with Inflammatory Bowel Diseases (IBD). We sought to examine the reasons for vaccine hesitancy in patients with IBD. In this case-control study, we performed a retrospective chart review of 1,349 IBD patients and 215 non-IBD patients seen at University of Maryland Medical Center, a tertiary referral medical center, between March 2020 and October 2021. Data obtained included demographics, vaccination records, disease history, number of IBD-related surgeries, and IBD medications. 813/1,349 (60.3%) IBD patients received at least one dose of either the Pfizer/BioNTech, Moderna, or Johnson & Johnson vaccines. In a multivariate logistic regression, COVID vaccination was found to be positively associated with older age (p-value = 1.65e-5), female sex (p = 0.00194), Asian and White races (p = 0.02330, 0.00169), number of clinic visits (p = 1.11e-08), and biologic use (p = 7.82e-5). There was no association between vaccination and other types of vaccination nor with the use of other IBD medications. There was a negative association between vaccination status and the total number of IBD related surgeries (p = 0.02857). In non-IBD patients, only the number of clinic visits was positively associated with COVID-19 vaccination. Although the majority of IBD patients are immunosuppressed, COVID-19 vaccination rate was only 60.3%. Younger adults, males, African Americans, and those requiring IBD-related surgeries were less likely to receive COVID-19 vaccine. Healthcare providers need to recognize these potential risk factors for COVID-19 vaccine hesitancy.

Emerging drugs for the treatment of inflammatory bowel disease.

INTRODUCTION: Anti-tumor necrosis factor (TNF)-α have been the mainstay therapy for Crohn's (CD) and ulcerative colitis (UC) for decades. With growing need for highly effective therapy, various therapeutic targets have been introduced including anti-integrins, anti-interleukin (IL) 12/23, selective anti-IL23, Janus Kinase (JAK) inhibitors, sphingosine-1-phosphate (S1P) receptor modulators, and mRNA-124 splicing agent. AREAS COVERED: The current state of available IBD therapies and those in development are reviewed, with recommendations made on positioning in clinical practice. EXPERT OPINION: Selecting and sequencing IBD therapies remains a clinical challenge. Disease phenotype, severity of symptoms, patient comorbidities, and prior drug exposure should be considered when considering therapy options. Anti-TNF remains a time-tested option that is effective in both UC and CD. The perception that newer biologics have slower onset of action is probably overestimated and providers should reconsider need for concurrent corticosteroid. JAK-inhibitors provide rapid symptom improvement in patients with moderate-severe UC. Due to safety concerns, it is recommended as a second-line therapy for UC. The goal for IBD treatment should be personalized, have rapid onset of action, induce durable clinical and endoscopic remission, and have excellent safety.

Female gender, dissatisfaction with weight, and number of IBD related surgeries as independent risk factors for eating disorders among patients with inflammatory bowel diseases.

BACKGROUND: The prevalence and risk factors of eating disorders among patients with IBD are poorly described in existing literature. Early recognition and intervention may influence clinical outcomes in both physical and mental health. The primary aims of this study were to describe the prevalence and identify risk factors for eating disorders among patients with IBD using a validated questionnaire, the EAT-26. METHODS: The EAT-26 was administered via email as an anonymous, unpaid, online survey to 1589 patients with an electronic medical record coded diagnosis of IBD (ulcerative colitis or Crohn's disease) who had visited our Digestive Health Center in the last 3 years. Demographics and IBD characteristics were also included in our survey. A score of 20 or higher on the EAT-26 portion of the survey was considered a positive screen for eating disorder risk. RESULTS: Fifteen (4.8%) survey participants screened positively for ED risk. These 15 participants who screened positively had statistically significant differences in self-identified gender (93% female, p = 0.031), happiness with current weight (80% dissatisfied with their current weight and trying to lose weight, p < 0.01), prior eating disorder diagnosis (20%, p < 0.01), and number of IBD related surgeries (27% having 3 or more, p = 0.013). CONCLUSIONS: This study identifies independent risk factors for eating disorder risk in patients with IBD including female gender, dissatisfaction with current weight, number of IBD related surgeries, and history of prior eating disorder diagnosis.

The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).

BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn's disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

Tangier Disease: An Unusual Cause of Chronic Diarrhea.

Tangier disease is a rare autosomal recessive disease resulting in cholesterol deposition in different organs. We report a case of a 52-year-old white man who presented for chronic diarrhea without significant findings on noninvasive testing. Subsequent colonoscopy revealed endoscopically normal mucosa, with random biopsies remarkable for foamy macrophages in the lamina propria. Genetic testing showed adenosine triphosphate-binding cassette transporter gene mutation with low high-density lipoprotein and low low-density lipoprotein. To the best of our knowledge, this is the first report of chronic diarrhea in a patient with Tangier disease without any other clear etiology.

Fecal Incontinence in Inflammatory Bowel Disease.

BACKGROUND: Fecal incontinence (FI) is frequently reported in inflammatory bowel disease (IBD). METHODS: We retrospectively reviewed data from the Study of a Prospective Adult Research Cohort with IBD registry. RESULTS: Three hundred forty-seven patients had Crohn disease and 145 had ulcerative colitis. 14.2% of patients reported FI. FI was associated with active disease. FI was not associated with disease location, phenotype, or perianal involvement. Greater than 50 years of age or 15 years of disease increased the odds of FI and remission decreased the odds of FI. CONCLUSIONS: Further research into the mechanism of FI in IBD is needed.

Nonalcoholic Fatty Liver Disease Is Common in IBD Patients However Progression to Hepatic Fibrosis by Noninvasive Markers Is Rare.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries and an increasing cause of end-stage liver disease and hepatocellular carcinoma. NAFLD is known to coexist in patients with inflammatory bowel disease (IBD). This study aims to examine the prevalence of NAFLD, as well as trends in NAFLD-associated fibrosis, in a well-characterized IBD cohort utilizing a validated noninvasive test. METHODS: We conducted a single-center retrospective chart review of patients at a large academic IBD center between 2007 and 2017. Patients with IBD and concurrent hepatic steatosis were identified. Charts were reviewed for baseline characteristics and laboratory data in order to calculate and trend NAFLD progression over time by a noninvasive marker, the NAFLD fibrosis score (NFS). RESULTS: Of 207 patients with IBD and concurrent NAFLD, NFS was able to be calculated for 138 patients at index diagnosis. A subsequent NFS was able to be calculated at 5-year follow-up for 56 patients. Over 5 years, 9 patients (16%) had worsening in NFS category, 4 patients (7%) had improvement in NFS category, and the remaining 43 patients (77%) stayed within their index NFS category. CONCLUSIONS: IBD patients with NAFLD tend to have stable liver disease over 4-6 years, and the risk of liver disease progression is low. This is the first study to document the progression of NAFLD by noninvasive testing over time.

Rapid Resolution of Vulvar Crohn's Disease With Ustekinumab.

In the evaluation of patients with inflammatory bowel disease, assessment of extraintestinal manifestations of disease is integral to clinical management. The patient described in this case is a 24-year-old woman with a history of inflammatory colonic Crohn's disease (CD) who presented to the hospital with one week of vaginal pain and swelling. Initial assessment focused on infectious etiologies, though final diagnosis of vulvar CD was made on biopsy. Clinical course and treatment of vulvar CD are poorly defined in existing literature. This case highlights the multidisciplinary management of inflammatory bowel disease patients and successful treatment of a rare extraintestinal manifestation with anti-interleukin 12/23 therapy.

Blistering autoimmune skin reaction following SHINGRIX vaccination in an ulcerative colitis patient: Case report and literature review.

Patients with inflammatory bowel disease, especially those on immunosuppressive therapy, are at higher risk of acquiring infectious diseases (Reich et al., 2016). For this reason, immunizations are routinely recommended in comprehensive inflammatory bowel disease care. SHINGRIX, a non-live recombinant herpes zoster vaccine, was approved by the Food and Drug Administration in 2017. Adults aged 50 and over are recommended to receive two doses of SHINGRIX. Unlike ZOSTAVAX® which is a live zoster vaccine that has been in use since 2006, SHINGRIX is safe for those on immunosuppression (Reich et al., 2016). The offside effects of SHINGRIX include injection-site erythema, tenderness, fatigue, and gastrointestinal upset. To our knowledge, blistering autoimmune skin disorders following SHINGRIX administration have not been reported. Here we discuss a case of a 74-year-old female patient with a history of ulcerative proctosigmoiditis on mesalamine who presented with a blistering skin disease after each SHINGRIX vaccination.

Isolated Pauci-Immune Pulmonary Capillaritis Associated with Hydrocarbon Inhalation and Marijuana Smoking: An Unusual Case of Severe Hypoxemia.

We present a case report of a patient with Isolated pauci-immune pulmonary capillaritis (IPIPC). A 40-year-old male presented with acute onset severe hypoxemic respiratory failure. He had just returned home from work as a cabinetmaker, where he experienced inhalational exposure to hydrocarbons and solvents, and had smoked a marijuana cigarette. He was hypotensive, and his chest imaging showed bilateral dependent infiltrates. His hypoxemia made little improvement after conventional ventilator support and broad-spectrum antibacterial therapy and he was considered too unstable to tolerate diagnostic bronchoscopy with bronchoalveolar lavage. His laboratory evaluation initially showed microscopic hematuria which later cleared, but other tests including serologic autoimmune assessment were negative, and he did not have any traditional risk factors for vasculitis. A video-assisted thoracoscopic lung biopsy revealed diffuse alveolar hemorrhage with pulmonary capillaritis on histopathology. He was diagnosed with IPIPC and initiated on immunosuppressive therapy. He was soon liberated from mechanical ventilation and improved to hospital discharge. Diffuse alveolar hemorrhage from Goodpasture's Syndrome has manifested following inhalation of hydrocarbons and following smoking. This has not previously been reported with IPIPC. Given the lack of other findings and risk factors, his IPIPC was likely associated with occupational exposures to hydrocarbons as a cabinetmaker compounded by marijuana smoking.

An Unusual Presentation of Baker's Cyst Rupture in an Inflammatory Bowel Disease Patient.

When evaluating a patient with acute onset unilateral leg pain and concurrent inflammatory bowel disease (IBD), keeping a broad differential diagnosis will allow for prompt diagnosis and management. The patient described in this case report is a 32-year-old male with inflammatory ileocolonic Crohn's disease (CD) status after ileocecectomy with perianal involvement and known Type 1 arthropathy. He presented with a three-day history of unilateral leg swelling and tenderness. Initial evaluation focused on possible thrombosis given the development of erythema and systemic symptoms. Final diagnosis was ruptured Baker's (popliteal) cyst. This pathology is not well described in existing literature, but should be considered in IBD patients given their chronic inflammatory state and common associated intra-articular pathology.

Expert opinion on interleukin-12/23 and interleukin-23 antagonists as potential therapeutic options for the treatment of inflammatory bowel disease.

INTRODUCTION: Blockade of interleukin (IL)-12 and IL-23 is a novel therapeutic target for inflammatory bowel disease (IBD). The monoclonal antibody targeting the shared p40 subunit of IL-12 and IL23, namely ustekinumab, has been approved for Crohn's disease (CD) and has demonstrated promising results in the treatment of ulcerative colitis. Several agents targeting the IL-23-specific p19 subunit are currently in various stages of development. These newer agents have the potential to provide safety benefits. AREAS COVERED: This review discusses the current state of IL-12/23 and IL-23 antagonists for the treatment of IBD. With multiple biologic classes available, we make recommendations for positioning of these agents in clinical practice. EXPERT OPINION: While tumor necrosis factor (TNF) antagonists remain the biologic of choice for majority of patients with moderate-to-severe IBD, IL-12/23, and IL-23 antagonists should be considered for first- or second-line therapy because of their efficacy in biologic-naïve and experienced patients. Additionally, IL-12/23 and IL-23 antagonists may be preferred over anti-TNF therapy in older patients who are at increased risk for infections and malignancy. The safety compared to anti-TNF may be even greater when one considers that concurrent immunosuppression is probably not necessary when using this class of drug, owing to the low rates of immunogenicity.

Improving High-resolution Impedance Manometry Using Novel Viscous and Super-viscous Substrates in the Supine and Upright Positions: A Pilot Study.

BACKGROUND/AIMS: Swallows with viscous or solid boluses in different body positions alter esophageal manometry patterns. Limitations of previous studies include lack of standardized viscous substrates and the need for chewing prior to swallowing solid boluses. We hypothesize that high-resolution impedance manometry (HRiM) using standardized viscous and super-viscous swallows in supine and upright positions improves sensitivity for detecting esophageal motility abnormalities when compared with traditional saline swallows. To establish normative values for these novel substrates, we recruited healthy volunteers and performed HRiM. METHODS: Standardized viscous and super-viscous substrates were prepared using "Thick-It" food thickener and a rotational viscometer. All swallows were administered in 5-mL increments in both supine and upright positions. HRiM metrics and impedance (bolus transit) were calculated. We used a paired two-tailed t test to compare all metrics by position and substrate. RESULTS: The 5-g, 7-g, and 10-g substrates measured 5000, 36 200, and 64 700 mPa∙sec, respectively. In 18 volunteers, we observed that the integrated relaxation pressure was lower when upright than when supine for all substrates (P < 0.01). The 10-g substrate significantly increased integrated relaxation pressure when compared to saline in the supine position (P < 0.01). Substrates and positions also affected distal contractile integral, distal latency, and impedance values. CONCLUSIONS: We examined HRiM values using novel standardized viscous and super-viscous substrates in healthy subjects for both supine and upright positions. We found that viscosity and position affected HRiM Chicago metrics and have potential to increase the sensitivity of esophageal manometry.