Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

2020 ◽  
Vol 12 (560) ◽  
pp. eaaz4047
Author(s):  
Antoine P. Fournier ◽  
Sara Martinez de Lizarrondo ◽  
Adrien Rateau ◽  
Axel Gerard-Brisou ◽  
Maximilian J. Waldner ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intestinal Mucosa ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Molecular Mri ◽  
Mucosal Tissues ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

scholarly journals Ultrasensitive Molecular Imaging of Mucosal Inflammation Using Leucocyte-Mimicking Particles Targeted to MAdCAM-1

2019 ◽  
Author(s):  
Antoine P. Fournier ◽  
Sara Martinez de Lizarrondo ◽  
Adrien Rateau ◽  
Axel Gerard-Brisou ◽  
Maximilian J. Waldner ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Adhesion Molecule ◽  
Intestinal Mucosa ◽  
Mucosal Inflammation ◽  
Resonance Imaging ◽  
Molecular Mri ◽  
Mucosal Tissues ◽  
Bowel Diseases ◽  
Inflammatory Bowel

ABSTRACTMucosal tissues line the digestive, respiratory, urinary, mammary and reproductive tracts and play critical roles in health and disease as the primary barrier between the external world and the inner body. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, that causes significant patient discomfort and can lead to organ damage. Here, we developed a new contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this new technique can detect low, subclinical levels of mucosal inflammation. Molecular MRI of MAdCAM-1 has thus potential applications in early diagnosis, longitudinal follow-up and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.One Sentence SummaryMolecular magnetic resonance imaging allows non-invasive evaluation of mucosal inflammation in clinically relevant experimental models.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

Immunomodulatory Effects of Flavonoids in the Prophylaxis and Treatment of Inflammatory Bowel Diseases: A Comprehensive Review

2018 ◽  
Vol 25 (28) ◽  
pp. 3374-3412 ◽  
Author(s):  
Daniela Ribeiro ◽  
Carina Proenca ◽  
Silvia Rocha ◽  
Jose L.F.C. Lima ◽  
Felix Carvalho ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Biological Properties ◽  
Human Diet ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Diseases (IBD) comprised of two disorders of idiopathic chronic intestinal inflammation that affect about three million people worldwide: Crohn’s disease and ulcerative colitis. Nowadays, the first-line of treatment for patients with mild to moderate symptoms of IBD is comprised of corticosteroids, immunosuppressants, antibiotics, and biological agents. Unfortunately, none of these drugs are curative, and their long-term use may cause severe side effects and complications. Almost 40% of IBD patients use alternative therapies to complement the conventional one, and flavonoids are gaining attention for this purpose. The biological properties of flavonoids are well documented and their antioxidant and anti-inflammatory activities have been arousing attention in the scientific community. Flavonoids are the most widely distributed polyphenols in plants and fruits, making part of the human diet. Taking into account that all ingested flavonoids are expected to exert biological actions at the gastrointestinal level, research on the modulatory effect of these compounds in IBD is of paramount importance. This review intends to summarize, in an integrated and comprehensive form, the effect of flavonoids, both in vitro and in vivo, in the different phases of the characteristic IBD inflammatory network.

scholarly journals Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases

2021 ◽  
Author(s):  
Huimin Chen ◽  
Xiaohan Wu ◽  
Chunjin Xu ◽  
Jian Lin ◽  
Zhanju Liu
Keyword(s):  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Mucosal Inflammation ◽  
Repair Processes ◽  
Microbial Invasion ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation and provide a precise overview of neutrophil functions in the pathogenesis of IBD.

scholarly journals Innate Immunity Modulation by the IL-33/ST2 System in Intestinal Mucosa

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Marina García-Miguel ◽  
M. Julieta González ◽  
Rodrigo Quera ◽  
Marcela A. Hermoso
Keyword(s):  
Ulcerative Colitis ◽  
Innate Immunity ◽  
Intestinal Mucosa ◽  
Inflammatory Bowel Diseases ◽  
The Body ◽  
Unknown Etiology ◽  
Adequate Food ◽  
Bowel Diseases ◽  
Surface Contact Area ◽  
Inflammatory Bowel

Innate immunity prevents pathogens from entering and spreading within the body. This function is especially important in the gastrointestinal tract and skin, as these organs have a large surface contact area with the outside environment. In the intestine, luminal commensal bacteria are necessary for adequate food digestion and play a crucial role in tolerance to benign antigens. Immune system damage can create an intestinal inflammatory response, leading to chronic disease including inflammatory bowel diseases (IBD). Ulcerative colitis (UC) is an IBD of unknown etiology with increasing worldwide prevalence. In the intestinal mucosa of UC patients, there is an imbalance in the IL-33/ST2 axis, an important modulator of the innate immune response. This paper reviews the role of the IL-33/ST2 system in innate immunity of the intestinal mucosa and its importance in inflammatory bowel diseases, especially ulcerative colitis.

scholarly journals Anthocyanins and intestinal barrier function: a review

2019 ◽  
Vol 5 ◽  
pp. 18-30 ◽  
Author(s):  
Jonathan C. Valdez ◽  
Bradley W. Bolling
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Berry Anthocyanins ◽  
Chronic Intestinal Inflammation

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.

scholarly journals Imaging in Inflammatory Bowel Diseases - Magnetic Resonance Imaging

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 26-31
Author(s):  
Hans Herfarth ◽  
Andreas G. Schreyer
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Magnetization Transfer ◽  
Diagnostic Value ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Line Imaging ◽  
Sensitivity Specificity

Diagnostic imaging techniques play an important role in the diagnosis and management of patients with inflammatory bowel diseases (IBDs). The approach should be guided by considerations of diagnostic accuracy, concerns about patient exposure to ionizing radiation, local expertise and tolerance of the endoscopic and/or imaging technique. In regard to the clinical diagnostic value (sensitivity, specificity and accuracy), no significant differences exist between CT and MRI for the evaluation of the extent of inflammation, stricturing, penetrating disease or extraluminal complications such as abscesses. Due to the absence of radiation exposure, MRI of the intestine is recommended as the first-line imaging modality in patients with suspected or established IBD. The focus of this review is the latest developments in MRI techniques to detect IBDs. Specifically, the use of new indices for the grading of inflammation or assessing bowel damage as well as innovative experimental approaches such as diffusion-weighted imaging or magnetization-transfer MRI to evaluate and quantify the degree of intestinal inflammation and fibrosis in stricturing Crohn's disease are discussed.

Oral Supplementation With Selected Lactobacillus Acidophilus Triggers Antimicrobial Response, Activation of Innate Lymphoid Cells Type 3 And Improves Colitis

2021 ◽  
Author(s):  
Jiří Hrdý ◽  
Aurélie Couturier-Maillard ◽  
Denise Boutillier ◽  
Carmen Lapadatescu ◽  
Philippe Blanc ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Lactobacillus Acidophilus ◽  
Target Genes ◽  
Intestinal Inflammation ◽  
Probiotic Strain ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Trinitrobenzene Sulfonic Acid ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that are illustrated by direct and indirect antimicrobial activity against several pathogens and improvement of intestinal inflammation. In this study, we evaluated the anti-inflammatory properties of the L. acidophilus strain BIO5768 and assessed the underlying mechanisms of action. BIO5768 was able to counteract the acute colitis that is induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was also able to alleviate intestinal inflammation induced by Citrobacter rodentium infection. Supplementation of naïve mice with either strain BIO5768 alone or as mixture, increased the gene expression of several target genes involved in immune signaling, including c-type lectin Reg3 gamma. Consistently, the ability of innate lymphoid cells to secrete IL-22 was enhanced in response to BIO5768. Interestingly, the aforementioned responses were shown to be independent of NOD2 and Th17 signaling in mice that were mono-colonized with BIO5768. In conclusion, we identify a new potential probiotic strain with the ability for the management of inflammatory bowel diseases, and provide some insights into its mode of action.

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