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 DIETARY FIBER GUAR GUM EXACERBATES COLONIC INFLAMMATION IN MULTIPLE EXPERIMENTAL MODELS OF INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S2-S3
Author(s):  
Divek V T Nair ◽  
Devendra Paudel ◽  
Margherita Cantorna ◽  
Vishal Singh
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dietary Fiber ◽  
Bowel Disease ◽  
Guar Gum ◽  
Control Group ◽  
Colonic Inflammation ◽  
Epithelial Injury ◽  
Amyloid A ◽  
Wide Range ◽  
Inflammatory Bowel

Abstract The role of fermentable dietary fibers in patients with inflammatory bowel disease (IBD) is not understood. Herein, we elucidated the effect of dietary fiber guar gum, commonly added to a wide range of processed foods, on colonic inflammation. The use of three different IBD models allowed us to examine the effect of guar gum on various aspects of human IBD, such as immune hyperactivity [IL-10 receptor (IL-10R) neutralization], epithelial injury [dextran sulfate sodium (DSS)], and infection [Citrobacter rodentium (CR)]-mediated inflammation. Wild-type (WT, C57BL/6) mice fed either control cellulose (insoluble fiber, aka non-fermentable fiber) or guar gum (soluble fiber, aka fermentable fiber, 7.5% w/w) were administered four weekly injections of IL-10R neutralizing antibody (α-IL-10R) to induce immune-hyperactivation mediated chronic colitis. Guar gum treated mice developed robust α-IL-10R mediated colitis. Guar gum fed mice had splenomegaly, colomegaly, elevated systemic proinflammatory markers [serum amyloid A (SAA), lipocalin 2 (Lcn2) and keratinocyte-derived chemokine (KC)] and elevated colonic Lcn2 and interleukin (IL)-1β, and histopathology scores compared to control, cellulose-fed, mice. Similar results were observed in Toll-like receptor 5 deficient mice, which are prone to develop microbiota-dependent colitis. Next, to examine the effect of guar gum on the epithelial injury model, mice were treated with DSS (1.4% w/v in drinking water) for seven days. The guar gum fed group developed severe colitis, including reduced body weight, diarrhea, rectal bleeding, shortening of colon length, and elevated levels of pro-inflammatory markers (Lcn2, KC, and SAA)compared to the control group. The last model to be tested was infection-induced colitis. Since inflammation is required to clear the infection, we hypothesized that guar gum fed mice might clear CR infection better than controls. To our surprise, guar gum fed WT mice shed higher numbers of CR in the feces than the cellulose group. The guar gum fed mice had lower body weights, colomegaly, an elevated level of colonic and serum Lcn2, and higher serum SAA than the control group. Collectively, guar gum failed to protect against CR-induced colonic pathology. Altogether, the work demonstrates that guar gum feeding may exacerbate colonic inflammation following immune-hyperactivation, chemical, and infectious injury. Cautioning IBD patients to monitor their consumption of guar gum fiber might be a way to reduce the severity of intestinal inflammation.

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 Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-24 ◽  
Author(s):  
Ana Cristina Alves de Almeida ◽  
Felipe Meira de-Faria ◽  
Ricardo José Dunder ◽  
Luis Paulo Bognoni Manzo ◽  
Alba Regina Monteiro Souza-Brito ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pharmacological Activity ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Biological Activities ◽  
Plant Secondary Metabolites ◽  
Experimental Models ◽  
Free Radical Scavengers ◽  
Recent Trends ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic and disrupted inflammation of the gastrointestinal tract. IBD have two main conditions, Crohn’s disease and ulcerative colitis, and have been extensively investigated in recent years. Antibiotics derived from salicylates, steroids, immunosuppressors, and anti-TNF therapy are part of the therapeutic arsenal for IBD. However, very often patients stop responding to treatments over the time. In this context, searching for alternative agents is crucial for IBD clinical management. Natural products derived from medicinal plants are an interesting therapeutic alternative, since several studies have proven effective treatments in animal models of intestinal inflammation. Several naturally occurring compounds are potent antioxidants, both as free radical scavengers and as modulators of antioxidant enzymes expression and activity. A number of natural compounds have also been proved to inhibit the release of proinflammatory cytokines, decreasing the activation of nuclear factorκB (NF-κB), which is important to the inflammatory response in IBD. The alkaloids are substances of a very diverse class of plant secondary metabolites; an extensive list of biological activities has been attributed to alkaloids, such as being anticholinergic, antitumor, diuretic, antiviral, antihypertensive, antiulcer, analgesic, and anti-inflammatory. In the present work, studies on the pharmacological activity of alkaloids in experimental models of IBD were reviewed.

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.

scholarly journals Attenuation of colonic inflammation by partial replacement of dietary linoleic acid with α-linolenic acid in a rat model of inflammatory bowel disease

2012 ◽  
Vol 108 (9) ◽  
pp. 1612-1622 ◽  
Author(s):  
Anupama Tyagi ◽  
Uday Kumar ◽  
Suryam Reddy ◽  
Vadakattu S. Santosh ◽  
Saazida B. Mohammed ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Linoleic Acid ◽  
Linolenic Acid ◽  
Bowel Disease ◽  
Partial Replacement ◽  
Myeloperoxidase Activity ◽  
Dietary Linoleic Acid ◽  
Colonic Inflammation ◽  
Inflammatory Bowel ◽  
The Impact

Increasing prevalence of inflammatory bowel disease may be due to imbalance in the intake ofn-6 andn-3 PUFA in the diet. This study investigates the impact of varying ratios of dietary linoleic acid (LA, 18 : 2n-6) to α-linolenic acid (ALA, 18 : 3n-3) on the inflammatory response in dextran sulphate sodium (DSS)-induced colitis. Weanling male Sprague–Dawley rats were divided into five groups: a non-colitic group with a LA:ALA ratio of 215 (CON-215), and colitic groups with LA:ALA ratios of 215 (DSS-215), 50 (DSS-50), 10 (DSS-10) and 2 (DSS-2). Blends of groundnut, palmolein and linseed oils were used to provide varying LA:ALA ratios. All the rats were fed the respective experimental isoenergetic diets containing 10 % fat for 90 d and DSS was administered during the last 11 d. Colonic inflammation was evaluated by clinical, biochemical and histological parameters. The results showed attenuation of colitis in the DSS-2 group as evidenced by significant reductions in disease activity index, mucosal myeloperoxidase activity (P < 0·05), alkaline phosphatase activity (P < 0·01) and increase in colon length (P < 0·01) compared to the groups fed with higher ratios (DSS-215). This was accompanied by significant reductions in mucosal proinflammatory cytokines TNF-α (P < 0·01) and IL-1β (P < 0·01) and improvement in the histological score. Further, ALA supplementation increased long-chain (LC)n-3 PUFA and decreased LCn-6 PUFA in colon structural lipids. These data suggest that substitution of one-third of LA with ALA (LA:ALA ratio 2) mitigates experimental colitis by down-regulating proinflammatory mediators.

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 Reducing Pain in Experimental Models of Intestinal Inflammation Affects the Immune Response

2021 ◽  
Author(s):  
Laura Golusda ◽  
Anja A Kühl ◽  
Britta Siegmund ◽  
Daniela Paclik
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Animal Models ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Intestinal Inflammation ◽  
Pain Medication ◽  
Experimental Models ◽  
Current Form ◽  
Inflammatory Bowel

Abstract The incidence of inflammatory bowel disease with its two main manifestations, colitis ulcerosa and Crohn’s disease, is rising globally year after year. There is still a tremendous need to study the underlying pathomechanisms and a well-established tool in order to better understand the disease are colitis models in rodents. Since the concept of the 3Rs was proposed by Russell and Burch, this would include pain medication in animal models of intestinal inflammation as a reduction of suffering. This review argues against pain medication because the administration of pain medication in its current form has an impact on the inflammatory process and the immune response, thus falsifying the results and the reproducibility and therefore leading to misconceptions.

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