Current Treatments For Inflammatory Bowel Disease Research Articles

Biological Response of Treatment with Saffron Petal Extract on Cytokine-Induced Oxidative Stress and Inflammation in the Caco-2/Human Leukemia Monocytic Co-Culture Model.

The pathogenesis of Inflammatory Bowel Disease (IBD) involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier. Current treatments for IBD often have significant limitations and adverse side effects, prompting a search for alternative therapeutic strategies. Natural products with anti-inflammatory and antioxidant properties have demonstrated potential for IBD management. There is increasing interest in exploring food industry waste as a source of bioactive molecules with healthcare applications. In this study, a co-culture system of Caco-2 cells and PMA-differentiated THP-1 macrophages was used to simulate the human intestinal microenvironment. Inflammation was induced using TNF-α and IFN-γ, followed by treatment with Saffron Petal Extract (SPE). The results demonstrated that SPE significantly attenuated oxidative stress and inflammation by downregulating the expression of pro-inflammatory mediators such as iNOS, COX-2, IL-1β, and IL-6 via modulation of the NF-κB pathway. Given that NF-κB is a key regulator of macrophage-driven inflammation, our findings support further investigation of SPE as a potential complementary therapeutic agent for IBD treatment.

Maximizing Treatment Options for IBD through Drug Repurposing.

Chronic inflammation characterizes Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC). Despite modest activity of disease in most UC patients, exacerbations occur, especially in those with severe symptoms, necessitating interventions, like colectomy. Current treatments for IBD, predominantly small molecule therapies, impose significant economic burdens. Drug repurposing offers a cost-effective alternative, leveraging existing drugs for novel therapeutic applications. This approach capitalizes on shared molecular pathways across diseases, accelerating therapeutic discovery while minimizing costs and risks. This article provides an overview of IBD and explores drug repurposing as a promising avenue for more effective and affordable treatments. Through computational and animal studies, potential drug candidates are categorized, offering insights into IBD pathogenesis and treatment strategies.

Intestinal Stromal Cells in the Turmoil of Inflammation and Defective Connective Tissue Remodeling in Inflammatory Bowel Disease.

In steady state, intestinal subepithelial myofibroblasts form a thin layer below the basement membrane. Unlike the rest of the stromal cells in the lamina propria, they express tensile proteins, guide epithelial regeneration, and sense luminal microbiota. Upon inflammation in inflammatory bowel disease (IBD), they express activation markers, accept trophic signaling by infiltrating neutrophils and macrophages, and are activated by cytokines from helper T cells to produce a narrow spectrum of cytokines and a wider spectrum of chemokines, attract cells of innate and adaptive immunity, orchestrate inflammatory responses, and qualitatively and quantitatively modify the extracellular matrix. Thus, beyond being structural tissue components, they assume active roles in the pathogenesis of complicated IBD. Discrimination between myofibroblasts and fibroblasts may be an oversimplification in light of single-cell sequencing data unveiling the complexity of multiple phenotypes of stromal cells with distinct roles and plasticity. Spatial transcriptomics revealed distinct phenotypes by histologic localization and, more intriguingly, the assembly of mucosal neighborhoods that support spatially distinct functions. Current IBD treatments target inflammation but fail in fibrostenotic or fistulizing disease. Baseline and recent findings on stromal cells, molecules, and pathways involved in disrupted extracellular matrix homeostasis are reviewed to provide relevant pharmacologic targets.

Antioxidant and Anti-Inflammatory Phytochemicals for the Treatment of Inflammatory Bowel Disease: A Systematic Review

Inflammatory bowel disease (IBD) remains a burden for patients with increasing prevalence in industrialized countries. Phytochemicals are non-nutrient plant derived bioactive substances with antioxidant and anti-inflammatory effects that may prove beneficial to IBD patients. This review aims to overview current evidence on the application and impact of isolated phytochemicals or phytochemicals contained in plant extracts and essential oils on patients suffering from IBD. A systematic literature search was conducted for studies relating to the use of phytochemicals for the treatment of IBD. Ultimately, 37 human clinical trials and 3 systematic reviews providing human IBD patient data relevant to phytochemicals as therapeutic agents were included. Phytochemicals in the form of curcumin, Plantago ovata seeds, polyphenon E, silymarin, resveratrol supplements or an herbal preparation of myrrh, chamomile and coffee charcoal have evidence from human clinical trials supporting their safety and beneficial effects. Cannabinoids improve quality of life but not IBD outcomes. The addition of probiotics like B. longum to fructo-oligosaccharides promote healthy composition of the gut microbiome. Phytochemicals like mastiha, anthocyanins, berberine, tormentil, T2, ecabet sodium and Pycnogenol need more well-designed trials. Systematic research on phytochemicals can lead to the discovery of useful therapeutics. These secondary metabolites can be incorporated in current IBD treatment strategies to limit side effects, promote mucosal healing and provide higher quality of life to patients.

Cardiovascular implications of inflammatory bowel disease: An updated review.

Emerging data highlights the heightened risk of atherosclerotic cardiovascular diseases (ASCVD) in patients with chronic inflammatory disorders, particularly those afflicted with inflammatory bowel disease (IBD). This review delves into the epidemiological connections between IBD and ASCVD, elucidating potential underlying mechanisms. Furthermore, it discusses the impact of current IBD treatments on cardiovascular risk. Additionally, the cardiovascular adverse effects of novel small molecule drugs used in moderate-to-severe IBD are investigated, drawing parallels with observations in patients with rheumatoid arthritis. This article aims to comprehensively evaluate the existing evidence supporting these associations. To achieve this, we conducted a meticulous search of PubMed, spanning from inception to August 2023, using a carefully selected set of keywords. The search encompassed topics related to IBD, such as Crohn's disease and ulcerative colitis, as well as ASCVD, including coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, conduction abnormalities, heart blocks, and premature coronary artery disease. This review encompasses various types of literature, including retrospective and prospective cohort studies, clinical trials, meta-analyses, and relevant guidelines, with the objective of providing a comprehensive overview of this critical intersection of inflammatory bowel disease and cardiovascular health.

Microbiota as key factors in inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is characterized by prolonged inflammation of the gastrointestinal tract, which is thought to occur due to dysregulation of the immune system allowing the host's cells to attack the GI tract and cause chronic inflammation. IBD can be caused by numerous factors such as genetics, gut microbiota, and environmental influences. In recent years, emphasis on commensal bacteria as a critical player in IBD has been at the forefront of new research. Each individual harbors a unique bacterial community that is influenced by diet, environment, and sanitary conditions. Importantly, it has been shown that there is a complex relationship among the microbiome, activation of the immune system, and autoimmune disorders. Studies have shown that not only does the microbiome possess pathogenic roles in the progression of IBD, but it can also play a protective role in mediating tissue damage. Therefore, to improve current IBD treatments, understanding not only the role of harmful bacteria but also the beneficial bacteria could lead to attractive new drug targets. Due to the considerable diversity of the microbiome, it has been challenging to characterize how particular microorganisms interact with the host and other microbiota. Fortunately, with the emergence of next-generation sequencing and the increased prevalence of germ-free animal models there has been significant advancement in microbiome studies. By utilizing human IBD studies and IBD mouse models focused on intraepithelial lymphocytes and innate lymphoid cells, this review will explore the multifaceted roles the microbiota plays in influencing the immune system in IBD.

Treatment of inflammatory bowel disease-Asian perspectives: the results of a multinational web-based survey in the 8th Asian Organization for Crohn's and Colitis meeting.

As the characteristics of inflammatory bowel disease (IBD) differ between Asians and Westerners, it is necessary to determine adequate therapeutic strategy for Asian IBD patients. We evaluated the current treatment of IBD in Asian countries/regions using a web-based survey. The Korean Association for the Study of Intestinal Diseases conducted a multinational web-based survey for current IBD care in Asia between September 16, 2020, and November 13, 2020. A total of 384 doctors treating IBD patients from 24 Asian countries/regions responded to the survey. Anti-tumor necrosis factor (TNF) agents, anti-integrins, and anti-interleukin-12/23 agents were available for use by 93.8%, 72.1%, and 70.1% of respondents in Asian countries/regions. Compared with a previous survey performed in 2014, an increased tendency for treatment with biologics, including anti-TNF agents, was observed. In the treatment of corticosteroid-refractory acute severe ulcerative colitis, 72.1% of respondents chose anti-TNF agents, followed by tacrolimus (11.7%). In the treatment of corticosteroid-refractory Crohn's disease, 90.4% chose anti-TNF agents, followed by thiopurines (53.1%), anti-interleukin-12/23 agents (39.3%), and anti-integrin agents (35.7%). In the treatment of Crohn's disease patients refractory to anti-TNF agents, the most preferred strategy was to measure serum levels of anti-TNF and anti-drug antibodies (40.9%), followed by empiric dose escalation or shortening of dosing intervals (25.3%). Although there were some differences, treatment strategies for patients with IBD were mostly similar among Asian doctors. Based on the therapeutic outcomes, it is necessary to identify the most appropriate therapeutic strategy for Asian IBD patients.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Executive Summary.

The burden of inflammatory bowel disease (IBD) (i.e., associated direct and indirect costs, prevalence of disease, personal impact to the individual and to caregivers) continues to increase in Canada. The prevalence of IBD has increased since Crohn's and Colitis Canada's 2018 Impact of IBD report from an estimated 270,000 Canadians living with IBD in 2018 to an estimated 322,600 Canadians living with IBD today in 2023. Consequently, associated costs of IBD have also dramatically increased from an estimated $2.57 billion in 2018 to an estimated $5.38 billion in 2023; this increase is due to multiple factors including increased prevalence of disease, inflation, and additional identified factors (e.g., presenteeism, costs of childcare). Beyond the economic impact of IBD, these diseases have a significant impact on people living with the disease and their caregivers, including different presentations of disease, different commonly associated extra-intestinal manifestations or comorbid conditions, and different barriers to accessing care. In this supplementary issue, we review: Evolving trends in the epidemiology of IBD; updated estimates of indirect and direct costs (including out-of-pocket costs) associated with IBD; information specific to IBD in children, adolescents, and seniors; issues related to IBD pertaining to sex and gender; information specific to risks associated with COVID-19 and cancer related to IBD; an overview of current treatments for IBD; and evolving care models, including access to care.

A32 PHAGE TREATMENT DELAYS ONSET OF CROHN’S-ASSOCIATED E. COLI DRIVEN COLITIS IN MICE COLONIZED WITH A DEFINED MICROBIOTA

Abstract Background Opportunistic pathogens have been postulated to drive dysregulated inflammation in inflammatory bowel disease (IBD). Indeed, adherent-invasive Escherichia coli (AIEC) isolated from IBD patients have pathobiont and pro-inflammatory characteristics. Current treatments for IBD suppress the immune response and do not target key microbial drivers, therefore novel strategies are required. Purpose Our aim was to determine whether bacteriophage therapy targeted against AIEC could reduce the severity of E. coli-driven colitis in gnotobiotic mice. Method Adult germ-free C57BL/6 mice were colonized with altered Schaedler-like flora (ASF) and E. coli NRG857c, a Crohn’s disease-associated bacterial isolate. Three weeks later, mice were treated with daily phage (selected by killing curves bioassays against E. coli NRG857c) or PBS for 2 weeks (n=6/group). Mice were then exposed to low-dose dextran sulfate sodium (2%; DSS) in drinking water for 5 days, followed by 2 days of water. PBS-treated mice (n=6) that received no DSS were used as additional negative controls. Mice were monitored daily for weight, stool consistency, and occult blood. At sacrifice, colon tissue was collected for histological analysis and fecal contents were cultured to determine bacterial load. In separate experiments, C57BL/6NTac-Il10em8Tac (IL-10-/-) mice were colonized with ASF-like microbiota and E. coli NRG857c. Three weeks later, mice (n=5) were treated with weekly phage or PBS (n=5) for 7 weeks. Mice were monitored weekly as described above. Result(s) Daily phage treatment reduced the severity of clinical symptoms induced by acute DSS administration (p < 0.001 vs. DSS-PBS treated mice). At endpoint, phage treatment was associated with lower histological scores as compared with DSS-PBS controls (p < 0.0001). A 1-log reduction in AIEC bacterial load was observed in phage treated mice as compared with DSS-PBS controls (p < 0.001). In IL-10-/- mice, weekly phage treatment delayed the spontaneous onset of colitis (p < 0.0001 vs. PBS-treated mice). At endpoint, mice treated with phage had lower colitis scores. Reduced weekly AIEC bacterial load was observed in phage-treated mice. Conclusion(s) Lytic phages, targeting a known AIEC pathobiont isolated from Crohn’s disease patients, ameliorate acute intestinal injury and delay onset of spontaneous colitis. Future work will investigate the mechanisms by which phage therapy prevents and treats colitis, to better inform clinical trial design. Disclosure of Interest None Declared

Treatment Effects of Natural Products on Inflammatory Bowel Disease In Vivo and Their Mechanisms: Based on Animal Experiments

Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory disease of the intestine that can be classified as ulcerative colitis (UC) and Crohn's disease (CD). Currently, the incidence of IBD is still increasing in developing countries. However, current treatments for IBD have limitations and do not fully meet the needs of patients. There is a growing demand for new, safe, and highly effective alternative drugs for IBD patients. Natural products (NPs) are used in drug development and disease treatment because of their broad biological activity, low toxicity, and low side effects. Numerous studies have shown that some NPs have strong therapeutic effects on IBD. In this paper, we first reviewed the pathogenesis of IBD as well as current therapeutic approaches and drugs. Further, we summarized the therapeutic effects of 170 different sources of NPs on IBD and generalized their modes of action and therapeutic effects. Finally, we analyzed the potential mechanisms of NPs for the treatment of IBD. The aim of our review is to provide a systematic and credible summary, thus supporting the research on NPs for the treatment of IBD and providing a theoretical basis for the development and application of NPs in drugs and functional foods.

Therapeutic Potential of Quercetin Loaded Nanoparticles: Novel Insights in Alleviating Colitis in an Experimental DSS Induced Colitis Model.

Oxidative stress is considered the main etiologic factor involved in inflammatory bowel disease (IBD). Integration of nanocarriers for natural therapeutic agents with antioxidant and anti-inflammatory potential is a novel promising candidate for curing IBD. Herein, the colonic antioxidant and anti-inflammatory effects of different concentrations of quercetin nanoparticles (QT-NPs) were evaluated using a dextran sulfate sodium (DSS)-induced colitis model. Following colitis induction, the efficacy and mechanistic actions of QT-NPs were evaluated by assessing lesion severity, molecular aids controlling oxidative stress and inflammatory response, and histopathological and immunohistochemistry examination of colonic tissues. Administration of QT-NPs, especially at higher concentrations, significantly reduced the disease activity index and values of fecal calprotectin marker compared to the colitic group. Colonic oxidant/antioxidant status (ROS, H2O2, MDA, SOD, CAT, GPX and TAC) was restored after treatment with higher concentrations of QT-NPs. Moreover, QT-NPs at levels of 20 mg/kg and, to a lesser extent, 15 mg/kg reduced Nrf2 and HO-1 gene expression, which was in line with decreasing the expression of iNOS and COX2 in colonic tissues. Higher concentrations of QT-NPs greatly downregulated pro-inflammatory cytokines; upregulated genes encoding occludin, MUC-2 and JAM; and restored the healthy architectures of colonic tissues. Taken together, these data suggest that QT-NPs could be a promising alternative to current IBD treatments.

Classic drugs in the time of new drugs: real-world, long-term outcomes of thiopurine monotherapy in 1016 patients with inflammatory bowel disease.

SummaryBackgroundThiopurines remain recommended as maintenance therapy in patients with inflammatory bowel disease (IBD). Despite their widespread use, long‐term effectiveness data are sparse and safety is an increasingly debated topic which thwarts proper delineation in the current IBD treatment algorithm.AimsTo document effectiveness and safety of thiopurine monotherapy in patients with IBD, using the population‐based IBD South‐Limburg (IBDSL) cohortMethodsAll patients starting thiopurine monotherapy as maintenance between 1991 and 2014 were included. Therapy was defined as effective if there was no escalation to biologicals, no course of corticosteroids, no surgery and no hospitalisation for active disease during treatment. Long‐term effectiveness was assessed by adjusting for differences in follow‐up using Kaplan–Meier analyses. Mid‐ to long‐term safety regarding cancer incidence and clinically relevant liver disease was documented.ResultsIn total, 1016 patients (643 Crohn's disease [CD]; 373 ulcerative colitis [UC]) received thiopurine monotherapy at a median of 15.2 (Q1‐Q3 4.2–48.5) months after diagnosis. During follow‐up, effectiveness rates at 1, 5 and 10 years were 64%, 45%, 32%, respectively, in CD and and 66%, 41%, 36%, respectively in UC. No statistically significant differences in effectiveness were observed after stratification for era of initiation (pre‐biological vs biological, CD: p = 0.56; UC: p = 0.43). Sixteen non‐melanoma skin cancers (incidence rate [IR] 3.33/1000 PY), five lymphomas (IR 1.04/1000 PY) and one urinary tract cancer (IR 0.21/1000 PY) were recorded. Two cases of portal hypertension were identified.ConclusionIn real‐world practice, thiopurine monotherapy remains effective, safe and durable for patients with CD or UC, including in the era of biologics.

Protective Effects of Pegylated Choline Acetyltransferase in a Murine Model of DSS Colitis

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, affects up to 3 million people in the United States alone, significantly worsens a patient’s quality of life, and is associated with a high financial burden. Current treatments for IBD are mainly biologicals that have significant side effects. No efficient pharmacological treatments are currently available for IBD. Previous studies established that activation of the vagus nerve‐based inflammatory reflex inhibits cytokine production and regulates immune responses through cholinergic signaling. Acetylcholine released by a T cell subset expressing choline acetyltransferase (ChAT), the enzyme that catalyzes the biosynthesis of acetylcholine, inhibits cytokine production via signaling through α7 nicotinic acetylcholine receptors (α7nAChR). However, the possibility of controlling inflammation by systemic administration of ChAT is unexplored. Here we examined the efficacy of ChAT in improving disease activity in a preclinical model of colitis. To prolong the half‐life of circulating ChAT, the protein was modified by covalently attaching repeating units of polyethylene glycol (PEG), resulting in enzymatically active PEG‐ChAT. We utilized a well‐established model of colitis ‐ dextran sulfate sodium induced colitis. Wild type C57/black 6 mice were exposed to 4% DSS (M.W 36 000‐50 000) in drinking water for 7 days prior to administration of PEG‐ChAT. Starting on day 8, animals received PEG‐ChAT or vehicle intraperitoneally twice per day for 7 days. PEG‐ ChAT treated mice showed a significantly lower disease activity index as compared with vehicle treated controls with the disease (d11 p=0.006 ChAT mice: 0.17DAI±0.05, n=9 versus vehicle mice: 0.66DAI±0.13, n=10). The decreased severity of colitis in PEG‐ChAT‐treated mice as compared with vehicle‐treated controls is further demonstrated by a significant improvement in body weight gain (d14 p=0.01 ChAT mice: ‐5.1%±1.1, n=10 versus vehicle mice: ‐15.5%±2.9, n=10) and colon length (p=0.006 ChAT mice: 7.15cm±0.2, n=10 versus vehicle mice: 6.2cm±0.2, n=10). In conclusion, PEG‐ChAT reduces disease activity in a preclinical model of colitis. Together these studies provide new insights into the role of PEG‐ChAT as an experimental anti‐inflammatory therapeutic modality for the treatment of IBD.

SNX10-mediated LPS sensing causes intestinal barrier dysfunction via a caspase-5-dependent signaling cascade.

Altered intestinal microbial composition promotes intestinal barrier dysfunction and triggers the initiation and recurrence of inflammatory bowel disease (IBD). Current treatments for IBD are focused on control of inflammation rather than on maintaining intestinal epithelial barrier function. Here, we show that the internalization of Gram-negative bacterial outer membrane vesicles (OMVs) in human intestinal epithelial cells promotes recruitment of caspase-5 and PIKfyve to early endosomal membranes via sorting nexin 10 (SNX10), resulting in LPS release from OMVs into the cytosol. Caspase-5 activated by cytosolic LPS leads to Lyn phosphorylation, which in turn promotes nuclear translocalization of Snail/Slug, downregulation of E-cadherin expression, and intestinal barrier dysfunction. SNX10 deletion or treatment with DC-SX029, a novel SNX10 inhibitor, rescues OMV-induced intestinal barrier dysfunction and ameliorates colitis in mice by blocking cytosolic LPS release, caspase-5 activation, and downstream signaling. Our results show that targeting SNX10 may be a new therapeutic approach for restoring intestinal epithelial barrier function and promising strategy for IBD treatment.

Metabolic Host-Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD).

Inflammatory bowel disease (IBD) is a family of conditions characterized by chronic, relapsing inflammation of the gastrointestinal tract. IBD afflicts over 3 million adults in the United States and shows increasing prevalence in the Westernized world. Current IBD treatments center on modulation of the damaging inflammatory response and carry risks such as immunosuppression, while the development of more effective treatments is hampered by our poor understanding of the molecular mechanisms of IBD pathogenesis. Previous genome-wide association studies (GWAS) have demonstrated that gene variants linked to the cellular response to microorganisms are most strongly associated with an increased risk of IBD. These studies are supported by mechanistic work demonstrating that IBD-associated polymorphisms compromise the intestine’s anti-microbial defense. In this review, we summarize the current knowledge regarding IBD as a disease of defects in host–microbe interactions and discuss potential avenues for targeting this mechanism for future therapeutic development.

Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook.

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disorder of the small intestine and colon. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), and it is a major factor for the development of colon cancer, referred to as colitis-associated cancer (CAC). The current treatment of IBD mainly includes the use of synthetic drugs and monoclonal antibodies. However, these drugs have side effects over long-term use, and the high relapse rate restricts their application. In the recent past, many studies had witnessed a surge in applying plant-derived products to manage various diseases, including IBD. Curcumin is a bioactive component derived from a rhizome of turmeric (Curcuma longa). Numerous in vitro and in vivo studies show that curcumin may interact with many cellular targets (NF-κB, JAKs/STATs, MAPKs, TNF-γ, IL-6, PPARγ, and TRPV1) and effectively reduce the progression of IBD with promising results. Thus, curcumin is a potential therapeutic agent for patients with IBD once it significantly decreases clinical relapse in patients with quiescent IBD. This review aims to summarize recent advances and provide a comprehensive picture of curcumin’s effectiveness in IBD and offer our view on future research on curcumin in IBD treatment.

P038 Factors Associated with Impaired Patient-Reported Outcomes and Work Productivity Among Patients with Ulcerative Colitis in Remission.

BACKGROUND: Real-world patients with ulcerative colitis (UC) in remission have reported impairment in many patient-reported outcome (PRO) measures. This study examined factors associated with PROs among UC patients in the Corrona Inflammatory Bowel Disease (IBD) Registry who were in remission. METHODS: Analysis included patients enrolled in the Corrona IBD Registry from May 3, 2017 through September 3, 2019 with a diagnosis of UC who were in remission (defined as partial Mayo score of <2) at the time of enrollment. Patient-Reported Outcomes Measurement Information System (PROMIS) and the Work Productivity and Activity Impairment (WPAI) questionnaires were collected at enrollment. Descriptive statistics were used to describe patient enrollment characteristics and were stratified by PROMIS status (moderate/severe ≥60 vs normal/mild <60) for Fatigue, Pain Interference, and Anxiety domains, and by WPAI impairment status (any vs none) for Presenteeism, Work Productivity Loss, and Activity Impairment domains. Characteristics with absolute standardized mean differences >0.10 suggest meaningful differences between groups defined by PRO impairment. RESULTS: Among patients enrolled in the registry, 731 were diagnosed with UC and 385 were in remission. UC patients in remission who reported moderate/severe fatigue were more likely to have a history of arthritis (n = 10/54,18.5% vs n = 26/325, 8.0%), had an earlier age of disease onset (mean, 33.4 vs 39.0 years), and increased urgency of defecation (n = 16/54, 29.6% vs n = 52/325, 16.0%) than those with normal/mild fatigue. Additionally, a higher proportion of patients with moderate/severe fatigue reported a history of corticosteroid use (n = 33/54, 61.1% vs n = 156/325, 48.0%), a history of antibiotic use (n = 15/54, 27.8% vs n = 49/325, 15.1%), as well as a shorter duration of current IBD treatment (mean, 2.3 vs 3.3 years).These treatment trends were also seen in patients who reported moderate/severe pain interference and anxiety vs normal/mild. A higher proportion of patients with moderate/severe fatigue reported current biologic treatment (n = 23/54, 42.6% vs n = 109/325, 33.5%) compared with those who reported normal/mild scores. Overall, those in remission reporting any Presenteeism impairment were more likely to have a history of arthritis (n = 11/97, 11.3% vs n = 11/157, 7.0%), to have greater urgency of defecation (n = 26/97, 26.8% vs n = 24/157, 15.3%), and to be currently treated with corticosteroids (n = 11/97, 11.3% vs n = 11/157, 7.0%) compared with those who reported none. The same trends were seen in those reporting any Work Productivity Loss: history of arthritis, n = 10/93 (10.8%) vs n = 10/144 (6.9%); urgency of defecation, n = 26/93 (28.0%) vs n = 23/144 (16.0%); and current corticosteroid treatment, n = 10/93 (10.8%) vs n = 10/144 (6.9%). In UC patients in remission reporting any Activity Impairment, the trend was seen for history of arthritis (n = 19/167, 11.4% vs n = 18/217, 8.3%), and urgency of defecation (n = 43/167, 25.7% vs n = 28/217,12.9%). CONCLUSION: Despite being in remission based on partial Mayo Score, patients with UC who reported impaired work productivity or had elevated fatigue, anxiety, or pain interference were more likely to have a history of arthritis and urgency. History of steroid use was seen more often in patients with impaired PROMIS scores. Further investigation is needed to address the unmet medical needs in these patients.

Faecal Microbiota Transplantation in Inflammatory Bowel Disease: Current Concepts and Future Challenges.

Dysbiosis has been repeatedly observed in inflammatory bowel disease (IBD) and is now recognized as an essential factor in the gut inflammatory process. IBD is a significant burden to health-care systems, mainly due to treatment-related costs. Available treatments have several limitations: up to 30% of patients are primary non-responders, and between 10 and 20% lose response per year, requiring a dose-escalation or a switch to another biologic. Hence, the current IBD treatment is not sufficient, and there is an urgent need to introduce new therapies in the management of these patients. Recently, the correction of dysbiosis has become an attractive approach from a therapeutic point of view. Faecal microbiota transplantation (FMT) appears as a reliable and potentially beneficial therapy in IBD patients. There is developing data that FMT for mild-to-moderately active UC is a safe and efficient therapy for the induction of remission. However, the current studies have different designs and have a short follow up, which makes clinical interpretation significantly difficult. There is a need for RCTs with a well-defined study cohort using FMT for the therapy of CD patients. The location, behavior, and severity of the disease should be taken into account. The goal of this manuscript is to review the data currently available on FMT and IBD, to explain FMT principles and methodology in IBD patients and to discuss some unresolved issues.

S3199 Cervical Cancer Screening and HPV Vaccine Awareness in Patients With IBD

INTRODUCTION: Studies have shown that patients with inflammatory bowel disease (IBD) have an increased risk of malignancy compared to the general population. In addition, cervical cancer screening in this high-risk group is often suboptimal. Human papillomavirus (HPV) vaccine is recommended, effective, and safe for all patients with IBD. This vaccine not only protects against cervical dysplasia in females, but it could also be effective in reducing the risk of anal, penile, and oral cancers in both genders. The aims of this study are to identify the rate of cervical cancer screening among patients with inflammatory bowel disease and to assess patients’ opinion regarding the HPV vaccine in addition to other vaccines currently recommended. METHODS: A self-designed anonymous survey was conducted on all adult (18–65) patients with IBD who presented for a routine clinic visit. The survey comprised of questions regarding gender, age, diagnosis, current IBD treatment, cervical smear test frequency, and vaccinations currently recommended for patients with IBD. Patients completed the survey in clinic under a physician’s supervision. RESULTS: Survey data from 18 IBD patients (mean age: 36 years, average IBD duration: 13 years) were analyzed. 50% of our patients were females and all of them were on immunomodulators or biologic therapy for IBD. Among surveyed women, 33% reported irregular cervical cancer screening and 33% did not remember when their previous testing was. Only 33% of women undergo testing regularly; 67% annually and 33% every 2 to 3 years. 55% of our patient population reported knowledge of HPV vaccine recommendation for IBD patients. CONCLUSION: Our study documents low awareness of HPV vaccine and suboptimal cervical testing in this outpatient population of IBD patients. A multidisciplinary approach to educate IBD patients about HPV vaccine and cervical testing recommendations is required to improve patients’ adherence and outcomes.Figure 1

Anti-inflammatory Effects of Northern Highbush Blueberry Extract on an In Vitro Inflammatory Bowel Disease Model

Blueberry anthocyanins have the ability to efficiently reach the GI tract and exhibit a broad range of biochemical effects. In the context of inflammatory bowel disease (IBD), they remain a promising complement to current IBD treatments. Here, we investigated the anti-inflammatory and antioxidant capabilities of Highbush blueberries in-vitro on two normal colon epithelial cell lines, NCM 356 and CCD 841 CoN using fluorescent microscopy and flow cytometry following stimulation with a pro-inflammatory cytokine cocktail. Treatment with blueberry extract revealed a significant decrease in nuclear and cytoplasmic generated reactive oxygen species (ROS) compared to controls. Additionally, the blueberry extract increased cell viability following treatment with the pro-inflammatory cytokine cocktail. A comparison with previous report on rice callus suspension culture (RCSC) revealed opposing trend with reference to the levels of nuclear and cytoplasmic ROS. It is likely that blueberry extract and RCSC employ different players and pathways to mitigate inflammation.