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Objective: We performed a systematic review for Complementary and Alternative Medicine [CAM] as defined by the National Institute of Health in Inflammatory Bowel Disease [IBD], ie Crohn's disease [CD] and ulcerative colitis [UC], with the exception of dietary and nutritional supplements, and manipulative therapies. Methods: A computerized search of databases [Cochrane Library, Pubmed/Medline, PsychINFO, and Scopus] through March 2014 was performed. We screened the reference sections of original studies and systematic reviews in English language for CAM in IBD, CD and UC. Randomized controlled trials [RCT] and controlled trials [CT] were referred and assessed using the Cochrane risk of bias tool. Results: A total of: 26 RCT and 3 CT for herbal medicine, eg aloe-vera gel, andrographis paniculata, artemisia absinthium, barley foodstuff, boswellia serrata, cannabis, curcumin, evening primrose oil, Myrrhinil intest®, plantago ovata, silymarin, sophora, tormentil, wheatgrass-juice and wormwood; 1 RCT for trichuris suis ovata; 7 RCT for mind/body interventions such as lifestyle modification, hypnotherapy, relaxation training and mindfulness; and 2 RCT in acupuncture; were found. Risk of bias was quite heterogeneous. Best evidence was found for herbal therapy, ie plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD. Conclusions: Complementary and alternative therapies might be effective for the treatment of inflammatory bowel diseases; however, given the low number of trials and the heterogeneous methodological quality of trials, further in-depth research is necessary. [ABSTRACT FROM AUTHOR]

The current hypothesis for the etiology of Crohn's disease proposes an excessive immune response, largely T-cell driven, possibly against endogenous bacteria. Standard therapy is therefore directed towards suppression of this immune response. An alternative theory of pathogenesis accounts for epidemiologic and pathophysiologic observations that have been hitherto underemphasized, namely, (1) genetic disorders with deficiencies in neutrophil function can give rise to a clinical and pathologic syndrome indistinguishable from Crohn's; (2) abnormal neutrophil function is well described in Crohn's disease; (3) a group of bacteria implicated in other chronic inflammatory disorders causes impairment of neutrophil function; and (4) 20th century environmental risk factors for Crohn's disease may directly suppress neutrophil function and may have led to a shift in the dominant gut flora with similar effects. We propose that some cases of Crohn's disease result from the interaction of environmental and genetic influences leading to impaired mucosal neutrophil function, resulting in failure to effectively clear intramucosal microbes effectively. While encompassing existing data, this hypothesis proposes a proximate defect in the mucosal immune response. If this paradigm were correct, new therapeutic approaches might involve strategies to alter intestinal flora and stimulate neutrophil function. [ABSTRACT FROM AUTHOR]

Heparin has been shown to ameliorate inflammatory bowel disease in several series. In addition to its anticoagulant properties, heparin has numerous other effects that may be beneficial in inflammatory bowel disease. Other sulfated polysaccharides, such as dextran sulfate, cause colitis in mice through unknown mechanisms. We postulate that dextran sulfate and heparin may act via similar pathways with opposite effects. To examine this thesis, the effect of heparin on dextran sulfate-induced colitis was studied. Swiss-Webster mice were given 5% dextran sulfate in their drinking water for five days to induce colitis. Heparin was given both therapeutically after the induction of colitis and prophylactically by subcutaneous injections, with saline injections given in controls. Histologic sections of colon were randomized and graded for colitis. Heparinized animals showed no significant difference in the pattern or severity of colitis when compared to control animals. It is concluded that heparin does not ameliorate the murine colitis induced by dextran sulfate in the doses given. [ABSTRACT FROM AUTHOR]

These authors conducted a case-control study to investigate whether air pollution levels are associated with the incidence of IBD. Overall, no association between the level of air pollution and IBD was identified; however, exposure to nitrogen dioxide and sulfur dioxide appeared to increase the risk of early-onset Crohn's disease and ulcerative colitis, respectively. [ABSTRACT FROM AUTHOR]

Background: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood., Methods: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code., Results: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models., Conclusions: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD) 1 -a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity 2 . However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

More than two decades ago it was discovered that nitric oxide (NO) concentrations in gas aspirated during colonoscopy were more than 100 times higher in patients diagnosed with Ulcerative Colitis (UC) than controls. While this provides a diagnostic opportunity, it has not been possible to perform in situ detection of NO via a non-invasive manner. This work presents the feasibility of in situ detection of NO by means of a capsule-like electrochemical gas sensor. Our in vivo results in a large animal model of intestinal inflammation show that NO can be directly detected at the site of inflammation and that it quickly dissipates to surrounding tissues, demonstrating the importance of in situ detection.

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., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Bile acids, such as chenodeoxycholic acid, play an important role in digestion but are also involved in intestinal motility, fluid homeostasis, and humoral activity. Colonic delivery of sodium chenodeoxycholate (CDC) has demonstrated clinical efficacy in treating irritable bowel syndrome with constipation but was associated with a high frequency of abdominal pain. We hypothesized that these adverse effects were triggered by local super-physiological CDC levels caused by an unfavorable pharmacokinetic profile of the delayed release formulation., Methods: We developed novel release matrix systems based on hydroxypropyl methylcellulose (HPMC) for sustained release of CDC. These included standard HPMC formulations as well as bi-layered formulations to account for potential delivery failures due to low colonic fluid in constipated patients. We evaluated CDC release profiles in silico (pharmacokinetic modeling), in vitro and in vivo in swine (pharmacokinetics, rectal manometry)., Results: For the delayed release formulation in vitro release studies demonstrated pH triggered dose dumping which was associated with giant colonic contractions in vivo. Release from the bi-layered HPMC systems provided controlled release of CDC while minimizing the frequency of giant contractions and providing enhanced exposure as compared to standard HPMC formulations in vivo., Discussion: Bi-phasic CDC release could help treat constipation while mitigating abdominal pain observed in previous clinical trials. Further studies are necessary to demonstrate the therapeutic potential of these systems in humans.

Background: South Asians have recently been identified as having a rapidly rising incidence and prevalence of inflammatory bowel disease (IBD) throughout the world. However, longitudinal phenotypic studies of South Asians living in the United States remain scarce., Methods: We retrospectively studied 171 South Asian patients with IBD treated at 2 US tertiary centers who presented between 2000 and 2016. South Asian IBD patients were randomly matched in a 1:2 ratio with sex and IBD subtype-matched (ulcerative colitis [UC] vs Crohn disease [CD]) white control patients (n = 342). Demographic and phenotypic characteristics were evaluated and compared between the 2 groups. Odds ratios (OR), logistic regression, and survival analysis were performed using R studio and STATA., Results: 81 South Asian patients and 162 white patients had CD, and 90 South Asians and 180 white patients had UC. Among the CD group, South Asian patients were diagnosed at a median older age (age 28) than white patients (21 years; P < 0.003). Fistulizing disease (24.1% vs 8.6%; P < 0.002), perianal disease (20.3% vs 2.5%; P < 0.005), and presentation of rectal pain (16.2% vs 2.9%; P < 0.001) were more common among South Asian patients with CD than among white patients. After adjusting for covariates, South Asian patients with CD were less likely to be placed on thiopurines (OR = 0.36; P < 0.007) or to receive more than 1 biologic (OR = 0.42; P < 0.040). South Asian patients with UC were less likely to have proctitis (10% vs 22.2%; P < 0.022) and more likely to have primary sclerosing cholangitis (n = 7 vs n = 2; P < 0.007). South Asian patients born in the United States or those who had migrated before age 5 were younger at the age of IBD diagnosis (age 18.9 vs 32.4; P < 0.0005)., Conclusion: We found unique demographic and phenotypic characteristics among South Asian patients, including more penetrating disease in those with CD and less proctitis among those with UC, along with altered medication use patterns. Distinct environmental exposures and a potentially unique genetic profile of South Asian patients may confer this variable phenotypic expression, influencing management of this increasingly at-risk population., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Anti-TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases., Aim: To examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti-TNFα agents for diseases other than inflammatory bowel disease (IBD) METHODS: A nationwide cohort study, based on Danish health registries, of all patients who utilised anti-TNFα agents for non-IBD indications. Included were patients, who had diseases for which anti-TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti-TNFα., Results: In total 17 018 individuals with autoimmune diseases were exposed to anti-TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63 308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4-2.8] and 2.0 [95% CI: 1.5-2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8-2.2] and 1.0 [95% CI:0.6-1.6], and for adalimumab 1.2 [95% CI: 0.8-1.8] and 0.6 [95% CI: 0.3-1.0]., Conclusions: Patients treated for autoimmune diseases with anti-TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases., (© 2019 John Wiley & Sons Ltd.)