Estrogen receptor actions in colitis

Abstract In recent years, researchers have demonstrated that estrogen and its receptors, aside from their role in regulating several biological functions, contribute to the development and progression/severity of inflammatory bowel diseases (IBDs). IBDs include both ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiological data indicate a clear difference in the incidence, severity, and complications of IBDs between sexes. Men present a higher risk of developing colitis than women and a higher risk of developing colorectal cancer, a common complication of this condition. However, fluctuations of estrogen levels have yielded inconsistent data, where oral contraceptives and hormone replacement therapy have been associated with an increased risk of IBDs in premenopausal women but significantly reduce disease activity after menopause. Likewise, improvement of symptoms related to CD has been reported during pregnancy, but not in UC, who often experience worsening symptoms. In the colonic epithelium, estrogen receptor β (ERβ) is the predominant form of the protein expressed, and it helps maintain normal epithelial function and organization. Preclinical data suggest that ER expression and activation via estrogen confers different responses on disease severity depending on the model used to induce colitis, which may reflect what is observed in patients with IBDs. Hence, this review aims to provide an overview of estrogen and its receptors, particularly ERβ, in the pathophysiology of IBDs.

Risk, Course, and Effect of SARS-CoV-2 Infection in Children and Adults with Chronic Inflammatory Bowel Diseases

Children ◽

10.3390/children8090753 ◽

2021 ◽

Vol 8 (9) ◽

pp. 753

Author(s):

Angelica Corrias ◽

Gian Mario Cortes ◽

Flaminia Bardanzellu ◽

Alice Melis ◽

Vassilios Fanos ◽

...

Keyword(s):

Bacterial Infections ◽

Immunosuppressive Treatment ◽

Epidemiological Data ◽

Adverse Outcomes ◽

Biologic Drugs ◽

Angiotensin Converting Enzyme 2 ◽

Increased Risk ◽

Bowel Diseases ◽

Susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases (IBD) are unclear and epidemiological data on the topic are still limited. There is some concern that patients with immuno-mediated diseases such as IBD, which are frequently treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 infection with its related serious adverse outcomes, including intensive care unit (ICU) admission and death. Corticosteroids, immunomodulators, and biologic drugs, which are commonly prescribed to these patients, have been associated with higher rates of severe viral and bacterial infections including influenza and pneumonia. It is not known whether these drugs can be so harmful as to justify their interruption during COVID-19 infection or if, on the contrary, patients with IBD can benefit from them. As shown by recent reports, it cannot be excluded that drugs that suppress the immune system can block the characteristic cytokine storm of severe forms of COVID-19 and consequently reduce mortality. Another cause for concern is the up-regulation of angiotensin converting enzyme-2 (ACE2) receptors that has been noticed in these patients, which could facilitate the entry and replication of SARS-CoV-2. The aim of this narrative review is to clarify the susceptibility of SARS-CoV-2 infection in patients with IBD, the clinical characteristics of patients who contract the infection, and the relationship between the severity of COVID-19 and immunosuppressive treatment.

Thrombosis in IBD in the Era of JAK Inhibition

Current Drug Targets ◽

10.2174/1389450121666200902164240 ◽

2020 ◽

Vol 22 (1) ◽

pp. 126-136

Author(s):

Virginia Solitano ◽

Gionata Fiorino ◽

Ferdinando D’Amico ◽

Laurent Peyrin-Biroulet ◽

Silvio Danese

Keyword(s):

Small Molecules ◽

Arterial Thrombosis ◽

Protective Role ◽

Jak Inhibitors ◽

Thrombotic Risk ◽

Increased Risk ◽

Bowel Diseases ◽

Thrombotic Complications ◽

Inflammatory Bowel ◽

Inflammatory Effect

: Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis. The interaction between inflammation and coagulation has been extensively studied. It is well-known that some drugs can influence the haemostatic system, but several concerns on the association between therapies and increased risk of thrombosis remain open. While biologics seem to have a protective role against thrombosis via their anti-inflammatory effect, some concerns about an increased risk of thrombosis with JAK inhibitors have been raised. We conducted a literature review to assess the association between biologics/small molecules and venous/arterial thrombotic complications. An increased risk of venous and arterial thrombosis was found in patients treated with corticosteroids, whereas anti-TNF were considered protective agents. No thromboembolic adverse event was reported with vedolizumab and ustekinumab. In addition, thromboembolic events rarely occurred in patients with ulcerative colitis (UC) after therapy with tofacitinib. The overall risk of both venous and arterial thrombosis was not increased based on the available evidence. Finally, in the era of JAK inhibitors, treatment should be individualized by evaluating the pre-existing potential thrombotic risk balanced with the intrinsic risk of the medication used.

The Role of Portal Vein Thrombosis in the Clinical Course of Inflammatory Bowel Diseases: Report on Three Cases and Review of the Literature

Gastroenterology Research and Practice ◽

10.1155/2012/916428 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Emanuele Sinagra ◽

Emma Aragona ◽

Claudia Romano ◽

Simonetta Maisano ◽

Ambrogio Orlando ◽

...

Keyword(s):

Portal Vein ◽

Portal Vein Thrombosis ◽

Vascular Complications ◽

Hepatic Abscess ◽

Vein Thrombosis ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Thromboembolism Events

Inflammatory bowel diseases are associated with an increased risk of vascular complications. The most important are arterial and venous thromboembolisms, which are considered as specific extraintestinal manifestations of inflammatory bowel diseases. Among venous thromboembolism events, portal vein thrombosis has been described in inflammatory bowel diseases. We report three cases of portal vein thrombosis occurring in patients with active inflammatory bowel disease. In two of them, hepatic abscess was present. Furthermore, we performed a systematic review based on the clinical literature published on this topic.

Immunoregulation in Inflammatory Bowel Diseases — Current Understanding and Innovation - Falk Symposium ◽

Increased risk of morbidity associated with immunomodulatory treatment in patients with inflammatory bowel diseases

10.1007/978-1-4020-5889-9_10 ◽

2007 ◽

pp. 85-98

Author(s):

J. -F. Colombel ◽

M. Toruner

Keyword(s):

Immunomodulatory Treatment ◽

Increased Risk ◽

Bowel Diseases ◽

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

Sclerosing cholangitis and inflammatory bowel disease: which comes first?

10.21508/1027-4065-2021-66-1-39-46 ◽

2021 ◽

Vol 66 (1) ◽

pp. 39-46

Author(s):

A. V. Nikitin ◽

G. V. Volynets

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Clinical Symptoms ◽

Cross Reactivity ◽

Formation Mechanisms ◽

Malignant Neoplasms ◽

Increased Risk ◽

Bowel Diseases ◽

Sclerosing cholangitis is one of the most common hepatologic extraintestinal manifestations of inflammatory bowel disease. The article discusses the phenotype of the combination of sclerosing cholangitis and inflammatory bowel disease. The authors present their theories of the etiopathogenesis of sclerosing cholangitis in patients with inflammatory bowel disease, as well as some features of the phenotype of both mixed and monogenic forms of diseases.Sclerosing cholangitis in combination with inflammatory bowel disease is commonly associated with pancolitis, but the endoscopically visualized activity of inflammatory bowel diseases is significantly lower and clinical symptoms are less pronounced. The authors have established that the patients with the combination of sclerosing cholangitis and inflammatory bowel disease are at the increased risk of developing malignant neoplasms. The formation mechanisms of a combination of inflammatory bowel disease and sclerosing cholangitis remain poorly understood, although this pathology is influenced by lymphocytic cross-reactivity, aberrant recognition of microbiotic epitopes and intestinal microbiota imbalance. New biological agents aimed at correcting the interaction between the immune system and target organs may provide new ways of treatment for sclerosing cholangitis associated with inflammatory bowel disease.

Optimization of antenatal monitoring approaches of women with chronic inflammatory bowel diseases

Reproductive Endocrinology ◽

10.18370/2309-4117.2021.57.84-92 ◽

2021 ◽

pp. 84-92

Author(s):

O.V. Bulavenko Bulavenko ◽

D.G. Konkov ◽

N.V. Kuzminova ◽

T.V. Lobastova ◽

I.V. Oleksienko

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Clinical Guidelines ◽

Cochrane Library ◽

Chronic Inflammatory Bowel Diseases ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Chronic Inflammatory Bowel

Chronic inflammatory bowel diseases (CIBD) affect patients at their peak of reproductive age. Clinical presentation of CIBD in pregnancy is associated with an increased risk of adverse effects in mother and fetus, including prematurity, low birth weight, increased indications for caesarean section. Thus optimizing of the CIBD diagnosis and treatment before and during pregnancy is essential to improve maternal and fetal outcomes.Research aim: to analyze the effectiveness of the CIBD clinical management at the stage of preconception and during pregnancy.Materials and methods. It was searched the Cochrane Library, WHO platform, clinical guidelines, and research reference database Medline. All potential studies have evaluated the clinical practice guidelines in women with CIBD for conception, pregnancy and breastfeeding. Recommendations related to the necessary laboratory and instrumental examination methods, therapeutic strategy, the safety of drugs for mother and fetus, the features of multidisciplinary antenatal observation, the timing and method of delivery of pregnant women with CIBD. Results. Treatment in the planning phase and pregnancy should be multidisciplinary, involving a gastroenterologist, obstetrician-gynecologist, primary care physician, pediatrician and a colorectal surgeon if necessary, as well as stakeholders from the association of patients with CIBD. Communication between these professionals is critical to avoid ambivalent or even conflicting counseling, which is an additional source of anxiety for patients, and also potentially dangerous for suboptimal prevention of clinical CIBD manifestation. Obtained results of the analysis will prevent laboratory and therapeutic polypharmacy and significantly improve the pregnancy outcome.Conclusions. Most women with CIBD had a physiological pregnancy and healthy children. However, some studies have linked CIBD to an increased risk of preterm birth and low birth weight infants. The development of national clinical guidelines will optimize and improve the quality of perinatal care to women with CIBD in the Ukraine, and will lead to a decrease in obstetric, fetal and neonatal complications.

Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms21093062 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3062 ◽

Cited By ~ 7

Author(s):

Takehiro Hirano ◽

Daisuke Hirayama ◽

Kohei Wagatsuma ◽

Tsukasa Yamakawa ◽

Yoshihiro Yokoyama ◽

...

Keyword(s):

Signaling Pathways ◽

Molecular Mechanisms ◽

T Helper 17 ◽

Colon Inflammation ◽

Immunological Mechanisms ◽

Increased Risk ◽

Bowel Diseases ◽

Cumulative Rate ◽

T Helper 17 Cell ◽

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

P261 Systematic review with meta-analysis: The impact of concomitant immune-mediated diseases on the disease course of inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.390 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S280-S281

Author(s):

M Attauabi ◽

M Zhao ◽

F Bendtsen ◽

J Burisch

Keyword(s):

Biologic Therapy ◽

Meta Analysis ◽

Multidisciplinary Care ◽

Disease Course ◽

Immune Mediated ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Meta Analyses ◽

The Impact

Abstract Background Several studies have shown an association between inflammatory bowel diseases [IBD] and immune-mediated diseases [IMIDs], but data on the impact of co-occurring IMIDs on IBD course are inconsistent. The aim of this study was to investigate the impact of co-occurring IMIDs on IBD phenotype and disease course. Methods PubMed and EMBASE were searched from database inception through December 2018 and updated in October 2019 for studies reporting prevalences or odds, risks or hazard ratios of IBD-related disease outcomes in patients with and without co-existing IMIDs. Meta-analyses were performed to estimate summary prevalences and risks of the outcomes which included disease extension, IBD-related surgery and hospitalisation, malignancy, mortality and need of medication (biologic therapy, steroids and immunomodulators). IMIDs were stratified into primary sclerosing cholangitis [PSC] and ‘IMIDs other than PSC’. Results A total of 93 studies comprising 14,307 IBD patients with IMIDs and 3,409,914 IBD patients without IMIDs were included in the study. Summary risks and prevalences with 95% confidence intervals for each outcome are presented in figures 1 and 2, respectively. The following results are all significant (p < 0.05). Compared with patients without co-occurring IMIDs, patients with ulcerative colitis [UC] and co-occurring IMIDs other than PSC more frequently received immunomodulators and steroids, and patients with Crohn’s disease [CD] and concomitant IMIDs other than PSC more often received biologic therapy. UC patients with co-existing IMIDs other than PSC more often underwent IBD-related surgery, while patients with CD and PSC received fewer surgeries. In addition, UC patients with co-occurring PSC were at increased risk for having extensive colitis, pancolitis, and malignancies. Patients with UC and PSC had a higher mortality rate, but no difference was found among patients with IMIDs other than PSC. PSC did not influence hospitalisation rates among IBD patients. Conclusion This meta-analysis found that IBD patients with co-existing IMIDs have a different disease course than patients without concomitant IMIDs. This study emphasises the importance of multidisciplinary care of IBD and that physicians caring for IBD patients need to be aware of IMIDs as a prognostic factor.

Nutrients in the Prevention of Osteoporosis in Patients with Inflammatory Bowel Diseases

Nutrients ◽

10.3390/nu12061702 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1702

Author(s):

Alicja Ewa Ratajczak ◽

Anna Maria Rychter ◽

Agnieszka Zawada ◽

Agnieszka Dobrowolska ◽

Iwona Krela-Kaźmierczak

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Mineral Density ◽

Low Bone Mineral Density ◽

Increased Risk ◽

Bowel Diseases ◽

Calcium Phosphorus ◽

Prevention Of Osteoporosis ◽

The chronic character of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, results in various complications. One of them is osteoporosis, manifested by low bone mineral density, which leads to an increased risk of fractures. The aetiology of low bone mineral density is multifactorial and includes both diet and nutritional status. Calcium and vitamin D are the most often discussed nutrients with regard to bone mineral density. Moreover, vitamins A, K, C, B12; folic acid; calcium; phosphorus; magnesium; sodium; zinc; copper; and selenium are also involved in the formation of bone mass. Patients suffering from inflammatory bowel diseases frequently consume inadequate amounts of the aforementioned minerals and vitamins or their absorption is disturbed, resulting innutritional deficiency and an increased risk of osteoporosis. Thus, nutritional guidelines for inflammatory bowel disease patients should comprise information concerning the prevention of osteoporosis.