Developing a Model to Study Commensal Translocation during IBD

2018 ◽  
Author(s):  
Kathy Yu
Keyword(s):  
Bacterial Translocation ◽  
Imaging Techniques ◽  
Coli Strain ◽  
The Body ◽  
Conjugation System ◽  
E Coli ◽  
Normal Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Future Work

Inflammatory bowel diseases (IBD) is severe inflammation of the gastrointestinal tract. This can lead to a breakdown of mucosal barriers, causing dissemination of commensal bacteria throughout the body. To better understand bacterial translocation during IBD, aim to develop a fluorescent microbiota in mice that we can interrogate using live imaging techniques.   Our preliminary experiments depleted commensals using broad-spectrum antibiotics,  and replaced these microbiota with a fluorescent E. coli strain. The length of time that E.coli stays in the mice gut were monitored. We show that E. coli can persist in the ‘germ-free’ mouse gut for at least 21 days; control mice lose all added E. coli by 8-14 days. The establishment of the E. coli colony suggests this could be a reasonable model to study bacterial translocation.  We are currently going to treat the colonized mice with DSS to induce colitis, and then to study translocation of E. coli by intravital microscopy. Considering E. coli is only a fraction of the normal microbiota and perhaps not a relevant model, future work aims at making a fluorescent microbiota consisting of multiple endogenous murine microbes. This will entail the use of a bacterial conjugation system  capable of ubiquitously transforming many microbial species.  

scholarly journals Anti-PD-1-Induced Hidradenitis Suppurativa

2021 ◽  
Vol 8 (1) ◽  
pp. 37-39
Author(s):  
Alexia Maillard ◽  
Damien Pastor ◽  
Rastine Merat
Keyword(s):  
Adverse Events ◽  
Hidradenitis Suppurativa ◽  
Checkpoint Inhibitors ◽  
Latency Period ◽  
The Body ◽  
Skin Reactions ◽  
Zinc Gluconate ◽  
Severe Acne ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Mucocutaneous adverse events are commonly observed under immune checkpoint inhibitors (ICIs) therapy. Here, we report the case of a 43-year-old male patient with a stage IIIC melanoma disease who developed hidradenitis suppurativa (HS) three months after the beginning of an anti-PD-1 (nivolumab) adjuvant therapy. The patient had no comorbidities other than obesity and severe acne during adolescence. After an unsuccessful course of lymecycline while he was still treated with nivolumab, he gradually improved under zinc gluconate therapy and, more importantly, after nivolumab cessation. HS is a recurrent follicular inflammatory disease in the apocrine gland-bearing areas of the body often associated with obesity, metabolic syndrome, tobacco smoking, inflammatory bowel diseases, psoriasis, and arthritis. In our patient, the latency period between drug initiation and onset of HS symptoms and the improvement after immunotherapy discontinuation, argued strongly in favor of an anti-PD-1-induced HS. Anti-PD-1 therapies often trigger T cells-mediated adverse events that mimic Th17-mediated inflammatory and neutrophilic diseases. We suggest that HS, as other pustular skin reactions and ICIs-induced neutrophilic colitis, can be part of the anti-PD-1 mucocutaneous adverse event spectrum.

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 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.

scholarly journals Role of Th17 Cells in the Pathogenesis of Human IBD

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Julio Gálvez
Keyword(s):  
Th17 Cells ◽  
Current Knowledge ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Inflammatory Conditions ◽  
Normal Microbiota ◽  
Bowel Diseases ◽  
Mucosal Homeostasis ◽  
Inflammatory Bowel

The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn’s disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD.

scholarly journals Functions of Macrophages in the Maintenance of Intestinal Homeostasis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Shuai Wang ◽  
Qianhong Ye ◽  
Xiangfang Zeng ◽  
Shiyan Qiao
Keyword(s):  
Prevention And Control ◽  
Wound Repair ◽  
The Body ◽  
Nutritional Regulation ◽  
Intestinal Homeostasis ◽  
Dietary Nutrients ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
And Control ◽  
Modulating Functions

Intestinal macrophages constitute the largest pool of macrophages in the body and have emerged as crucial sentinels for pathogen recognition and elimination. The source and development of intestinal macrophages, as well as their distinct properties have been well documented. Intestinal macrophages exert their functions in the maintenance of intestinal homeostasis by shaping host-microbiota symbiosis, managing gut inflammation, crosstalking with T cells, and facilitating wound repair. Recently, nutritional regulation of intestinal macrophages has attracted substantial attention and is becoming a promising approach to disease prevention and control. Understanding the mechanisms employed by intestinal macrophages in mediating intestinal immune homeostasis and inflammation, as well as the mode of action of dietary nutrients in the modulating functions of intestinal macrophages, represents an opportunity to prevent and control inflammatory bowel diseases.

scholarly journals Mutation of Tyr137 of the universalEscherichia colifimbrial adhesin FimH relaxes the tyrosine gate prior to mannose binding

IUCrJ ◽  
2017 ◽  
Vol 4 (1) ◽  
pp. 7-23 ◽  
Author(s):  
Said Rabbani ◽  
Eva-Maria Krammer ◽  
Goedele Roos ◽  
Adam Zalewski ◽  
Roland Preston ◽  
...  
Keyword(s):  
Ethylenediaminetetraacetic Acid ◽  
Hydrophobic Interactions ◽  
Binding Pocket ◽  
Lectin Domain ◽  
E Coli ◽  
Ligand Free ◽  
Mannose Binding ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Dynamics Simulations

The most prevalent diseases manifested byEscherichia coliare acute and recurrent bladder infections and chronic inflammatory bowel diseases such as Crohn's disease.E. coliclinical isolates express the FimH adhesin, which consists of a mannose-specific lectin domain connectedviaa pilin domain to the tip of type 1 pili. Although the isolated FimH lectin domain has affinities in the nanomolar range for all high-mannosidic glycans, differentiation between these glycans is based on their capacity to form predominantly hydrophobic interactions within the tyrosine gate at the entrance to the binding pocket. In this study, novel crystal structures of tyrosine-gate mutants of FimH, ligand-free or in complex with heptyl α-D-O-mannopyranoside or 4-biphenyl α-D-O-mannopyranoside, are combined with quantum-mechanical calculations and molecular-dynamics simulations. In the Y48A FimH crystal structure, a large increase in the dynamics of the alkyl chain of heptyl α-D-O-mannopyranoside attempts to compensate for the absence of the aromatic ring; however, the highly energetic and stringent mannose-binding pocket of wild-type FimH is largely maintained. The Y137A mutation, on the other hand, is the most detrimental to FimH affinity and specificity: (i) in the absence of ligand the FimH C-terminal residue Thr158 intrudes into the mannose-binding pocket and (ii) ethylenediaminetetraacetic acid interacts strongly with Glu50, Thr53 and Asn136, in spite of multiple dialysis and purification steps. Upon mutation, pre-ligand-binding relaxation of the backbone dihedral angles at position 137 in the tyrosine gate and their coupling to Tyr48viathe interiorly located Ile52 form the basis of the loss of affinity of the FimH adhesin in the Y137A mutant.

scholarly journals BODY-MASS ESTIMATION IN PALEONTOLOGY: A REVIEW OF VOLUMETRIC TECHNIQUES

2016 ◽  
Vol 22 ◽  
pp. 133-156 ◽  
Author(s):  
Charlotte A. Brassey
Keyword(s):  
Body Mass ◽  
Laser Scanning ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
The Body ◽  
Estimation Methods ◽  
Mass Estimation ◽  
Surface Laser ◽  
Body Mass Estimation ◽  
Future Work

AbstractBody mass is a key parameter for understanding the physiology, biomechanics, and ecology of an organism. Within paleontology, body mass is a fundamental prerequisite for many studies considering body-size evolution, survivorship patterns, and the occurrence of dwarfism and gigantism. The conventional method for estimating fossil body mass relies on allometric scaling relationships derived from skeletal metrics of extant taxa, but the recent application of three-dimensional imaging techniques to paleontology (e.g., surface laser scanning, computed tomography, and photogrammetry) has allowed for the rapid digitization of fossil specimens. Volumetric body-mass estimation methods based on whole articulated skeletons are therefore becoming increasingly popular. Volume-based approaches offer several advantages, including the ability to reconstruct body-mass distribution around the body, and their relative insensitivity to particularly robust or gracile elements, i.e., the so-called ‘one bone effect.’ Yet their application to the fossil record will always be limited by the paucity of well-preserved specimens. Furthermore, uncertainties with regards to skeletal articulation, body density, and soft-tissue distribution must be acknowledged and their effects quantified. Future work should focus on extant taxa to improve our understanding of body composition and increase confidence in volumetric model input parameters.

scholarly journals Ultrasound of the Small Bowel in Crohn’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Emma Calabrese ◽  
Francesca Zorzi ◽  
Francesco Pallone
Keyword(s):  
Crohn’S Disease ◽  
Gastrointestinal Tract ◽  
Crohn's Disease ◽  
Imaging Techniques ◽  
Careful Evaluation ◽  
Intravenous Contrast ◽  
Endoscopic Techniques ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Exciting Area

Several radiological and endoscopic techniques are now available for the study of inflammatory bowel diseases. In everyday practice, the choice of the technique to be used depends upon its availability and a careful evaluation of diagnostic accuracy, clinical usefulness, safety, and cost. The recent development of innovative and noninvasive imaging techniques has led to a new and exciting area in the exploration of the gastrointestinal tract, especially in Crohn’s disease patients by using ultrasound with oral or intravenous contrast.

scholarly journals Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Li-Ming Chen ◽  
Chun-Hui Bao ◽  
Yu Wu ◽  
Shi-Hua Liang ◽  
Di Wang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Metabolic Pathway ◽  
Bowel Disease ◽  
The Body ◽  
Metabolic Enzyme ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Bloody Stools ◽  
The Relationship

AbstractInflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.

scholarly journals Up-to-date overview of imaging techniques in the diagnosis and management of inflammatory bowel diseases

2019 ◽  
Vol 14 (1) ◽  
pp. 19-25
Author(s):  
Katarzyna B. Biernacka ◽  
Dobromiła Barańska ◽  
Piotr Grzelak ◽  
Elżbieta Czkwianianc ◽  
Katarzyna Szabelska-Zakrzewska
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Imaging Techniques ◽  
Diagnosis And Management ◽  
Bowel Diseases ◽  
Inflammatory Bowel
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