scholarly journals Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

2017 ◽  
Vol 1 (4) ◽  
pp. 333-349 ◽  
Author(s):  
Ian O'Neill ◽  
Zoe Schofield ◽  
Lindsay J. Hall
Keyword(s):  
Critical Period ◽  
Immune Modulation ◽  
Future Directions ◽  
Immune Development ◽  
Disease States ◽  
Physiological Processes ◽  
Inflammatory Bowel ◽  
Different Strains ◽  
Immune Maturation

The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout our lifetime and have been shown to modulate specific immune cells and pathways. Notably, reductions in this genus have been associated with several diseases, including inflammatory bowel disease. In this review, we provide an overview of bifidobacteria profiles throughout life and how different strains of bifidobacteria have been implicated in immune modulation in disease states. The focus will be examining preclinical models and outcomes from clinical trials on immune-linked chronic conditions. Finally, we highlight some of the important unresolved questions in relation to Bifidobacterium-mediated immune modulation and implications for future directions, trials, and development of new therapies.

scholarly journals tRNA-Derived Small RNAs: Novel Epigenetic Regulators

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2773
Author(s):  
Joonhyeong Park ◽  
Se Hee Ahn ◽  
Myung Geun Shin ◽  
Hak Kyun Kim ◽  
Suhwan Chang
Keyword(s):  
Epigenetic Regulation ◽  
Small Rnas ◽  
Immune Modulation ◽  
Cpg Islands ◽  
Multiple Roles ◽  
Systemic Lupus ◽  
Physiological Processes ◽  
Epigenetic Regulators ◽  
The Many

An epigenetic change is a heritable genetic alteration that does not involve any nucleotide changes. While the methylation of specific DNA regions such as CpG islands or histone modifications, including acetylation or methylation, have been investigated in detail, the role of small RNAs in epigenetic regulation is largely unknown. Among the many types of small RNAs, tRNA-derived small RNAs (tsRNAs) represent a class of noncoding small RNAs with multiple roles in diverse physiological processes, including neovascularization, sperm maturation, immune modulation, and stress response. Regarding these roles, several pioneering studies have revealed that dysregulated tsRNAs are associated with human diseases, such as systemic lupus, neurological disorder, metabolic disorder, and cancer. Moreover, recent findings suggest that tsRNAs regulate the expression of critical genes linked with these diseases by a variety of mechanisms, including epigenetic regulation. In this review, we will describe different classes of tsRNAs based on their biogenesis and will focus on their role in epigenetic regulation.

Harnessing targeted DNA methylation and demethylation using dCas9

2019 ◽  
Vol 63 (6) ◽  
pp. 813-825 ◽  
Author(s):  
Christian Pflueger ◽  
Tessa Swain ◽  
Ryan Lister
Keyword(s):  
Dna Methylation ◽  
Disease Modeling ◽  
Aberrant Methylation ◽  
Dna Modification ◽  
Future Directions ◽  
Disease States ◽  
Genome Regulation ◽  
Fundamental Understanding ◽  
Functional Relevance

Abstract DNA methylation is an essential DNA modification that plays a crucial role in genome regulation during differentiation and development, and is disrupted in a range of disease states. The recent development of CRISPR/catalytically dead CRISPR/Cas9 (dCas9)-based targeted DNA methylation editing tools has enabled new insights into the roles and functional relevance of this modification, including its importance at regulatory regions and the role of aberrant methylation in various diseases. However, while these tools are advancing our ability to understand and manipulate this regulatory layer of the genome, they still possess a variety of limitations in efficacy, implementation, and targeting specificity. Effective targeted DNA methylation editing will continue to advance our fundamental understanding of the role of this modification in different genomic and cellular contexts, and further improvements may enable more accurate disease modeling and possible future treatments. In this review, we discuss strategies, considerations, and future directions for targeted DNA methylation editing.

scholarly journals The Role of Endogenous Antimicrobial Peptides in Modulating Innate Immunity of the Ocular Surface in Dry Eye Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 721
Author(s):  
Youssof Eshac ◽  
Rachel L. Redfern ◽  
Vinay Kumar Aakalu
Keyword(s):  
Antimicrobial Peptides ◽  
Dry Eye ◽  
Ocular Surface ◽  
Immune Modulation ◽  
Therapeutic Potential ◽  
Eye Diseases ◽  
Innate Immune ◽  
Disease States ◽  
Ocular Surface Diseases

The ocular surface has the challenging responsibility of maintaining a clear moist refractive surface while protecting the eye from exogenous pathogens and the environment. Homeostasis of the ocular surface, including its innate immune components, is altered in ocular surface disease states. In this review, we focus on antimicrobial peptides and the role they play in the immune response of the ocular surface during healthy states and dry eye diseases. Antimicrobial peptides are of special interest to the study of the ocular surface because of their various roles that include microbial threat neutralization, wound healing, and immune modulation. This review explores current literature on antimicrobial peptides in ocular surface diseases and discusses their therapeutic potential in ocular surface diseases and dry eye.

Vedolizumab

2016 ◽  
Vol 29 (5) ◽  
pp. 503-515 ◽  
Author(s):  
Mara Poulakos ◽  
Jade D. Machin ◽  
Julienne Pauly ◽  
Yasmin Grace
Keyword(s):  
Intestinal Barrier ◽  
Relevant Information ◽  
Intestinal Barrier Function ◽  
Disease States ◽  
Bowel Diseases ◽  
Biologic Response ◽  
Patients At Risk ◽  
Inflammatory Bowel ◽  
The Brain

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders affecting the gastrointestinal (GI) tract that encompass Crohn’s disease (CD) and ulcerative colitis (UC). In these disease states, epithelial damage of the intestinal mucosa is evident due to increased lymphocyte trafficking to the area, which affects the normal intestinal barrier function. Currently available pharmacotherapy can be limited in terms of efficacy and associated toxicities. Newer agents have emerged, including the monoclonal antibody natalizumab, which antagonizes integrin, an important component within the inflammation cascade. Natalizumab works by modulating both the GI and brain biologic responses and as a result there is risk of the opportunistic infection known as progressive multifocal leukoencephalopathy (PML), putting patients at risk for severe disability and death. Vedolizumab, another integrin inhibitor, is selective for modulating the gut biologic response but not the brain, consequently decreasing the risk for PML. To generate information regarding the role of vedolizumab in the treatment of IBD, a literature search was conducted, yielding 7 phase I to III clinical trials. This article serves as a summary of efficacy, safety, and other relevant information from clinical studies to explore the role of vedolizumab in the treatment of CD and UC.

scholarly journals Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver–Gut Axis

2021 ◽  
Vol 22 (3) ◽  
pp. 1397
Author(s):  
Niklas Grüner ◽  
Jochen Mattner
Keyword(s):  
Bile Acids ◽  
Current Knowledge ◽  
Gut Bacteria ◽  
Intestinal Lumen ◽  
Clostridioides Difficile ◽  
Physiological Processes ◽  
Local Site ◽  
Inflammatory Bowel ◽  
And Function

After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs are subsequently re-absorbed in the terminal ileum and are transported back for recycling to the liver. Some of them, however, reach the colon and change their physicochemical properties upon modification by gut bacteria, and vice versa, BAs also shape the composition and function of the intestinal microbiota. This mutual interplay of both BAs and gut microbiota regulates many physiological processes, including the lipid, carbohydrate and energy metabolism of the host. Emerging evidence also implies an important role of this enterohepatic BA circuit in shaping mucosal colonization resistance as well as local and distant immune responses, tissue physiology and carcinogenesis. Subsequently, disrupted interactions of gut bacteria and BAs are associated with many disorders as diverse as Clostridioides difficile or Salmonella Typhimurium infection, inflammatory bowel disease, type 1 diabetes, asthma, metabolic syndrome, obesity, Parkinson’s disease, schizophrenia and epilepsy. As we cannot address all of these interesting underlying pathophysiologic mechanisms here, we summarize the current knowledge about the physiologic and pathogenic interplay of local site microbiota and the enterohepatic BA metabolism using a few selected examples of liver and gut diseases.

scholarly journals Antimicrobial Peptides in Gastrointestinal Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Simon Jäger ◽  
Eduard F. Stange ◽  
Jan Wehkamp
Keyword(s):  
Antimicrobial Peptides ◽  
Intestinal Inflammation ◽  
Disease States ◽  
Mucosal Surfaces ◽  
Bowel Diseases ◽  
Inflammatory Processes ◽  
Complex Events ◽  
Inflammatory Bowel ◽  
Adaptive Immune Systems

Acute and chronic inflammations of mucosal surfaces are complex events in which the effector mechanisms of innate and adaptive immune systems interact with pathogenic and commensal bacteria. The role of constitutive and inducible antimicrobial peptides in intestinal inflammation has been investigated thoroughly over the recent years, and their involvement in various disease states is expanded ever more. Especially in the intestines, a critical balance between luminal bacteria and the antimicrobial peptides is essential, and a breakdown in barrier function by impaired production of defensins is already implicated in Crohn's disease. In this paper, we focus on the role of antimicrobial peptides in inflammatory processes along the gastrointestinal tract, while considering the resident and pathogenic flora encountered at the specific sites. The role of antimicrobial peptides in the primary events of inflammatory bowel diseases receives special attention.

scholarly journals Endocytosis of Intestinal Tight Junction Proteins: In Time and Space

2020 ◽  
Author(s):  
Prashant Nighot ◽  
Thomas Ma
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Intracellular Trafficking ◽  
Intestinal Epithelial ◽  
Dynamic Regulation ◽  
Physiological Processes ◽  
Vital Functions ◽  
Inflammatory Bowel ◽  
Endocytic Regulation

Abstract Eukaryotic cells take up macromolecules and particles from the surrounding milieu and also internalize membrane proteins via a precise process of endocytosis. The role of endocytosis in diverse physiological processes such as cell adhesion, cell signaling, tissue remodeling, and healing is well recognized. The epithelial tight junctions (TJs), present at the apical lateral membrane, play a key role in cell adhesion and regulation of paracellular pathway. These vital functions of the TJ are achieved through the dynamic regulation of the presence of pore and barrier-forming proteins within the TJ complex on the plasma membrane. In response to various intracellular and extracellular clues, the TJ complexes are actively regulated by intracellular trafficking. The intracellular trafficking consists of endocytosis and recycling cargos to the plasma membrane or targeting them to the lysosomes for degradation. Increased intestinal TJ permeability is a pathological factor in inflammatory bowel disease (IBD), and the TJ permeability could be increased due to the altered endocytosis or recycling of TJ proteins. This review discusses the current information on endocytosis of intestinal epithelial TJ proteins. The knowledge of the endocytic regulation of the epithelial TJ barrier will provide further understanding of pathogenesis and potential targets for IBD and a wide variety of human disease conditions.

scholarly journals The Emerging Role of Epitranscriptomics in Cancer: Focus on Urological Tumors

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 552 ◽  
Author(s):  
João Lobo ◽  
Daniela Barros-Silva ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Tumor Model ◽  
The Cancer Genome Atlas ◽  
Dependent Manner ◽  
Rna Molecules ◽  
Disease States ◽  
Physiological Processes ◽  
Cancer Models ◽  
Cancer Genome Atlas ◽  
Urogenital Neoplasms

Epitranscriptomics has gained ground in recent years, especially after the advent of techniques for accurately studying these mechanisms. Among all modifications occurring in RNA molecules, N6-methyladenosine (m6A) is the most frequent, especially among mRNAs. m6A has been demonstrated to play important roles in many physiological processes and several disease states, including various cancer models (from solid to liquid tumors). Tumor cells’ epitranscriptome is indeed disrupted in a way to promote cancer-prone features, by means of up/downregulating m6A-related players: the so-called writers, readers and erasers. These proteins modulate m6A establishment, removal and determine mRNAs fate, acting in a context-dependent manner, so that a single player may act as an oncogenic signal in one tumor model (methyltransferase like 3 (METTL3) in lung cancer) and as a tumor suppressor in another context (METTL3 in glioblastoma). Despite recent advances, however, little attention has been directed towards urological cancer. By means of a thorough analysis of the publicly available TCGA (The Cancer Genome Atlas) database, we disclosed the most relevant players in four major urogenital neoplasms—kidney, bladder, prostate and testicular cancer—for prognostic, subtype discrimination and survival purposes. In all tumor models assessed, the most promising player was shown to be Vir like m6A methyltransferase associated (VIRMA), which could constitute a potential target for personalized therapies.

scholarly journals The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)—A Critical Review

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1973
Author(s):  
Dominika Jakubczyk ◽  
Katarzyna Leszczyńska ◽  
Sabina Górska
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Bowel Disease ◽  
Genetic Background ◽  
Inflammatory State ◽  
Inflammatory Bowel ◽  
Potential Strategy ◽  
Different Strains

Inflammatory bowel disease (IBD), which affects millions of people worldwide, includes two separate diseases: Crohn’s disease (CD) and ulcerative colitis (UC). Although the background (chronic inflammatory state) and some of the symptoms of CD and UC are similar, both diseases differ from each other. It is becoming clear that a combination of many factors, in particular genetic background, host immune response and microbial reduced diversity status are associated with IBD. One potential strategy to prevent/treat IBD is gut modulation by probiotics. Over the last twenty years, many publications have focused on the role of probiotics in the course of IBD. The review discusses the utility of different strains of probiotics, especially Bifidobacterium spp., in all factors potentially involved in the etiology of IBD. The probiotic modulatory properties among different study models (cell lines, animal models of colitis, clinical study) are discussed and probiotic usefulness is assessed in relation to the treatment, prevention, and remission of diseases.

Role of faecal gas analysis for the diagnosis of IBD

2011 ◽  
Vol 39 (4) ◽  
pp. 1079-1080 ◽  
Author(s):  
Chris S.J. Probert
Keyword(s):  
Gastrointestinal Diseases ◽  
Gas Analysis ◽  
Non Invasive ◽  
Disease States ◽  
Faecal Samples ◽  
Volatile Organic ◽  
Headspace Gas ◽  
Inflammatory Bowel ◽  
Symptoms And Signs

The diagnosis of IBD (inflammatory bowel disease) is based on the clinical evaluation of symptoms and signs leading to a series of investigations. The investigations used are often unpleasant for patients; they are invasive, costly and potentially dangerous. Patients often report that the odour of flatus, or the gas emitted from faeces, is abnormal during a flare of their IBD. Our group has characterized the VOCs (volatile organic compounds) in the headspace gas emitted from faecal samples from healthy subjects, from patients with infectious diarrhoea and from those with Crohn's disease or ulcerative colitis, both in relapse and remission. Painstaking analysis of gas chromatography–MS data (VOC profiling) has revealed patterns of compounds that are strongly associated with specific infectious diseases and with IBD. These compounds represent a change in the microflora and/or the metabolism of bacteria and/or the epithelium in disease states. These profiles offer a potential for rapid non-invasive assessment of a range of infectious and non-infectious gastrointestinal diseases. The study of VOCs may lead to a better understanding of the pathogenesis of IBD.

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