scholarly journals Unraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease

2020 ◽  
Vol 26 (12) ◽  
pp. 1787-1795 ◽  
Author(s):  
Mariana Ferreira-Duarte ◽  
Maria Manuela Estevinho ◽  
Margarida Duarte-Araújo ◽  
Fernando Magro ◽  
Manuela Morato
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Biologic Drugs ◽  
Multifunctional Protein ◽  
Expression Activity ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.

scholarly journals Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 126 ◽  
Author(s):  
Israr Khan ◽  
Naeem Ullah ◽  
Lajia Zha ◽  
Yanrui Bai ◽  
Ashiq Khan ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Gut Flora ◽  
Core Microbiome ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

scholarly journals The Impact of Farnesoid X Receptor Activation on Intestinal Permeability in Inflammatory Bowel Disease

2012 ◽  
Vol 26 (9) ◽  
pp. 631-637 ◽  
Author(s):  
Maja Stojancevic ◽  
Karmen Stankov ◽  
Momir Mikov
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Tract ◽  
Intestinal Inflammation ◽  
Strong Support ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
The Impact

The most important function of the intestinal mucosa is to form a barrier that separates luminal contents from the intestine. Defects in the intestinal epithelial barrier have been observed in several intestinal disorders such as inflammatory bowel disease (IBD). Recent studies have identified a number of factors that contribute to development of IBD including environmental triggers, genetic factors, immunoregulatory defects and microbial exposure. The current review focuses on the influence of the farnesoid X receptor (FXR) on the inhibition of intestinal inflammation in patients with IBD. The development and investigation of FXR agonists provide strong support for the regulatory role of FXR in mucosal innate immunity. Activation of FXR in the intestinal tract decreases the production of proinflammatory cytokines such as interleukin (IL) 1-beta, IL-2, IL-6, tumour necrosis factor-alpha and interferon-gamma, thus contributing to a reduction in inflammation and epithelial permeability. In addition, intestinal FXR activation induces the transcription of multiple genes involved in enteroprotection and the prevention of bacterial translocation in the intestinal tract. These data suggest that FXR agonists are potential candidates for exploration as a novel therapeutic strategy for IBD in humans.

The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Joerg Ermann ◽  
Mederbek Matmusaev ◽  
Emma Haley ◽  
Clemens Braun ◽  
Felix Jost ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Intestinal Microbiome ◽  
Intestinal Immune System ◽  
Pharmacokinetic Properties ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Human And Mouse

ABSTRACT Background and Aims : Mouse and human data implicates the NOD1 and NOD2 sensors of the intestinal microbiome and the associated signal transduction via the RIPK2 kinase as a potentially key signaling node for the development of Inflammatory Bowel Disease (IBD) and an attractive target for pharmacologic intervention. The TRUC mouse model of IBD has been strongly indicated for evaluating the impact of RIPK2 antagonism on intestinal inflammation based on previous studies with NOD1, NOD2 and RIPK2 knockout mice. Methods. We identified and profiled the BI 706039 molecule as a potent and specific functional inhibitor of both human and mouse RIPK2 and with favorable pharmacokinetic properties. We dosed BI 706039 in the spontaneous TRUC mouse model from aged day 28 through aged day 56. Results : Oral, daily administration of BI 706039 caused dose-responsive and significant improvement in colonic histopathological inflammation, colon weight and terminal levels of protein normalized fecal lipocalin (all p< 0.001). These observations correlated with dose-responsively increasing systemic levels of the BI 706039 compound, splenic molecular target engagement of RIPK2 and modulation of inflammatory genes in the colon. Conclusions : A relatively low oral dose of a potent and selective RIPK2 inhibitor can block the signaling interface between the intestinal microbiome and the intestinal immune system and significantly improve disease associated intestinal inflammation.

scholarly journals P048 Intestinal inflammation and microbiome diversity are conserved more in consecutive pregnancies among women with inflammatory bowel disease compared to healthy controls

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S156-S158
Author(s):  
M Agrawal ◽  
L Tarassishin ◽  
A Rendon ◽  
C Hillenbrand ◽  
A Debebe ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Mode Of Delivery ◽  
Alpha Diversity ◽  
Infection Prophylaxis ◽  
Healthy Controls ◽  
Microbiome Diversity ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.

scholarly journals Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3589
Author(s):  
Yasser Morsy ◽  
Nathalie Brillant ◽  
Yannick Franc ◽  
Michael Scharl ◽  
Marcin Wawrzyniak ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gene Locus ◽  
Intestinal Inflammation ◽  
Severe Disease ◽  
Mrna Levels ◽  
Disease Course ◽  
Risk Gene ◽  
Inflammatory Bowel ◽  
The Impact

Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.

scholarly journals Oral Manifestations of Inflammatory Bowel Disease and the Role of Non-Invasive Surrogate Markers of Disease Activity

Medicines ◽  
2020 ◽  
Vol 7 (6) ◽  
pp. 33 ◽  
Author(s):  
Davide Giuseppe Ribaldone ◽  
Selvaggia Brigo ◽  
Michela Mangia ◽  
Giorgio Maria Saracco ◽  
Marco Astegiano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Immunosuppressive Agents ◽  
Oral Lesions ◽  
Oral Manifestations ◽  
Biologic Drugs ◽  
Non Invasive ◽  
Inflammatory Bowel ◽  
Work Up

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), can be associated with several extra-intestinal manifestations requiring a multidisciplinary management both in terms of work-up and therapy. Oral lesions are common in patients with IBD, with a prevalence ranging from 5% to 50%. These can represent an oral location of IBD as well as a side-effect of drugs used to treat the intestinal disease. Oral manifestations, occurring in patients with IBD, can be divided in nonmalignant, specific, and non-specific ones, and malignant lesions. While there is undoubtedly a need to search for an IBD in patients with oral lesions associated with intestinal symptoms, the work-up of those with an exclusive oral lesion should be personalized. Fecal calprotectin is a non-invasive marker of intestinal inflammation and may be used to select which patients need to undergo endoscopic examination, thereby avoiding unnecessary investigations. The pharmacological armamentarium to treat oral lesions associated with IBD includes topical or systemic corticosteroids, immunosuppressive agents, and biologic drugs.

scholarly journals Microbiota and Drug Response in Inflammatory Bowel Disease

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 211
Author(s):  
Martina Franzin ◽  
Katja Stefančič ◽  
Marianna Lucafò ◽  
Giuliana Decorti ◽  
Gabriele Stocco
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Pharmacological Therapy ◽  
Microbial Composition ◽  
Biologic Drugs ◽  
Immune Mediated ◽  
Mutualistic Relationship ◽  
Inflammatory Bowel ◽  
The Impact ◽  
The Relationship

A mutualistic relationship between the composition, function and activity of the gut microbiota (GM) and the host exists, and the alteration of GM, sometimes referred as dysbiosis, is involved in various immune-mediated diseases, including inflammatory bowel disease (IBD). Accumulating evidence suggests that the GM is able to influence the efficacy of the pharmacological therapy of IBD and to predict whether individuals will respond to treatment. Additionally, the drugs used to treat IBD can modualate the microbial composition. The review aims to investigate the impact of the GM on the pharmacological therapy of IBD and vice versa. The GM resulted in an increase or decrease in therapeutic responses to treatment, but also to biotransform drugs to toxic metabolites. In particular, the baseline GM composition can help to predict if patients will respond to the IBD treatment with biologic drugs. On the other hand, drugs can affect the GM by incrementing or reducing its diversity and richness. Therefore, the relationship between the GM and drugs used in the treatment of IBD can be either beneficial or disadvantageous.

scholarly journals Food Additive Guar Gum Aggravates Colonic Inflammation in Experimental Models of Inflammatory Bowel Disease

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1142-1142
Author(s):  
Divek VT Nair ◽  
Devendra Paudel ◽  
Divya Prakash ◽  
Vishal Singh
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Guar Gum ◽  
Intestinal Inflammation ◽  
Experimental Models ◽  
Colonic Inflammation ◽  
Epithelial Injury ◽  
Amyloid A ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Objectives Guar gum, a soluble fiber, is commonly used as a thickener, stabilizer, and source of fiber in processed foods. The food industry has been encouraged to fortify foods with refined guar gum due to its numerous beneficial effects on the human gut and metabolic health. However, we have limited knowledge on whether processed guar gum holds the same physiological effects as its naturally occurring counterpart. In this study, we examined the impact of refined guar gum on intestinal inflammation. Methods We employed three different experimental models of inflammatory bowel disease (IBD)—(1) immune hyperactivity [IL-10 receptor (IL-10R) neutralization], (2) epithelial injury [dextran sulfate sodium (DSS)], and 3) infection [Citrobacter rodentium (CR)]- mediated inflammation—to elucidate the effect of refined guar gum on IBD comprehensively. The colitis development was examined by serological, histological, and immunological parameters. Results Wild-type (WT, C57BL/6) mice receiving guar gum (7.5% w/w) containing diet (GuD) along with α-IL-10R displayed severe colonic inflammation—as characterized by an enlarged spleen, thickening of the colon, and elevated systemic [serum amyloid A (SAA), lipocalin 2 (Lcn2) and keratinocyte-derived chemokine (KC)] and colonic [Lcn2 and interleukin (IL)-1β] markers of inflammation—when compared to mice fed control (cellulose) diet. Histological examination of colonic sections displayed distorted and elongated crypt structure and reduced goblet cells. Inline, GuD-fed mice maintained on DSS (1.4% w/v) for seven days exhibited relatively worsened colitis compared to the control diet-fed group. Specifically, GuD-fed mice showed a more abrupt loss in body weight, diarrhea, rectal bleeding, shortening of colon length, and heightened proinflammatory cytokines, including KC, SAA, and Lcn2. In contrast to what we observed with immune hyperactivation and epithelial injury models, GuD did not exacerbate the CR-induced infectious colitis; however, no sign of protection was evident in the GuD-fed group. Conclusions This study collectively demonstrates that refined guar gum may heighten the intestinal inflammation in patients with IBD. Funding Sources This work is supported by a Career Development Award from the Crohn's & Colitis Foundation.

scholarly journals Diet–Microbiota Interactions in Inflammatory Bowel Disease

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1533
Author(s):  
Kohei Sugihara ◽  
Nobuhiko Kamada
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Chronic Inflammatory Disease ◽  
Host Cells ◽  
Intestinal Homeostasis ◽  
New Therapeutic Approaches ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD is largely unknown, it is widely thought that diet contributes to the development of IBD. Diet shapes the composition of the gut microbiota, which plays critical roles in intestinal homeostasis. In contrast, intestinal inflammation induces gut dysbiosis and may affect the use of dietary nutrients by host cells and the gut microbiota. The interaction of diet and the gut microbiota is perturbed in patients with IBD. Herein, we review the current knowledge of diet and gut microbiota interaction in intestinal homeostasis. We also discuss alterations of diet and gut microbiota interaction that influence the outcome and the nutritional treatment of IBD. Understanding the complex relationships between diet and the gut microbiota provides crucial insight into the pathogenesis of IBD and advances the development of new therapeutic approaches.

scholarly journals Novel trends with biologics in inflammatory bowel disease: sequential and combined approaches

2021 ◽  
Vol 14 ◽  
pp. 175628482110066
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Loris Riccardo Lopetuso ◽  
Franco Scaldaferri ◽  
Matteo Neri ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Current Knowledge ◽  
New Drugs ◽  
Management Algorithm ◽  
History Of Disease ◽  
History Of ◽  
Complex Landscape ◽  
Inflammatory Bowel ◽  
The Impact

Inflammatory bowel disease (IBD) management has changed dramatically over the past 20 years, after the introduction of targeted biological therapies. However, the impact of these new drugs in changing the natural history of disease is still under debate. Recent evidence seems to suggest that the extent of their efficacy might be, at least partially, dependent on the timing of their introduction and on the subsequent management strategy. In this complex landscape, the potential role for a more dynamic approach with treatments based on sequencing and combining targeted therapies has been explored only minimally so far. In this review, we aim to explore the potential biological rationale behind the use of sequential and combination therapies in IBD, to summarise the current knowledge on this topic and to propose a management algorithm that combines these notions.

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