Interplay between Gut Lymphatic Vessels and Microbiota

Lymphatic vessels play a distinctive role in draining fluid, molecules and even cells from interstitial and serosal spaces back to the blood circulation. Lymph vessels of the gut, and especially those located in the villi (called lacteals), not only serve this primary function, but are also responsible for the transport of lipid moieties absorbed by the intestinal mucosa and serve as a second line of defence against possible bacterial infections. Here, we briefly review the current knowledge of the general mechanisms allowing lymph drainage and propulsion and will focus on the most recent findings on the mutual relationship between lacteals and intestinal microbiota.

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Lymphatic Valves and Lymph Flow in Cancer-Related Lymphedema

Cancers ◽

10.3390/cancers12082297 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2297

Author(s):

Drishya Iyer ◽

Melanie Jannaway ◽

Ying Yang ◽

Joshua P. Scallan

Keyword(s):

Bacterial Infections ◽

Complex Disease ◽

Current Knowledge ◽

Lymphatic Vessels ◽

Developed Countries ◽

Lymph Flow ◽

Fatty Tissue ◽

Limited Mobility ◽

Valve Development ◽

Lymphatic Vasculature

Lymphedema is a complex disease caused by the accumulation of fluid in the tissues resulting from a dysfunctional or damaged lymphatic vasculature. In developed countries, lymphedema most commonly occurs as a result of cancer treatment. Initially, impaired lymph flow causes edema, but over time this results in inflammation, fibrotic and fatty tissue deposition, limited mobility, and bacterial infections that can lead to sepsis. While chronically impaired lymph flow is generally believed to be the instigating factor, little is known about what pathophysiological changes occur in the lymphatic vessels to inhibit lymph flow. Lymphatic vessels not only regulate lymph flow through a variety of physiologic mechanisms, but also respond to lymph flow itself. One of the fascinating ways that lymphatic vessels respond to flow is by growing bicuspid valves that close to prevent the backward movement of lymph. However, lymphatic valves have not been investigated in cancer-related lymphedema patients, even though the mutations that cause congenital lymphedema regulate genes involved in valve development. Here, we review current knowledge of the regulation of lymphatic function and development by lymph flow, including newly identified genetic regulators of lymphatic valves, and provide evidence for lymphatic valve involvement in cancer-related lymphedema.

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Vascular endothelial cell specification in health and disease

Angiogenesis ◽

10.1007/s10456-021-09785-7 ◽

2021 ◽

Author(s):

Corina Marziano ◽

Gael Genet ◽

Karen K. Hirschi

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Current Knowledge ◽

Vascular Malformations ◽

Immune Surveillance ◽

Vascular Endothelial Cell ◽

Lymphatic Vessels ◽

Lymphatic Endothelial Cell ◽

The Body ◽

Vascular Networks

AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

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A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽

10.3390/nu13072428 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2428

Author(s):

Małgorzata Guz ◽

Witold Jeleniewicz ◽

Anna Malm ◽

Izabela Korona-Glowniak

Keyword(s):

Colorectal Cancer ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Knowledge ◽

Vital Role ◽

Disease States ◽

Health And Disease ◽

Dietary Components ◽

Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

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Rho GTPases as Key Molecular Players within Intestinal Mucosa and GI Diseases

Cells ◽

10.3390/cells10010066 ◽

2021 ◽

Vol 10 (1) ◽

pp. 66

Author(s):

Rashmita Pradhan ◽

Phuong A. Ngo ◽

Luz d. C. Martínez-Sánchez ◽

Markus F. Neurath ◽

Rocío López-Posadas

Keyword(s):

Intestinal Mucosa ◽

Rho Gtpases ◽

Current Knowledge ◽

Cell Types ◽

Effector Proteins ◽

Special Focus ◽

Specific Cell ◽

Rho Proteins

Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.

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Cell-to-Cell Communication by Host-Released Extracellular Vesicles in the Gut: Implications in Health and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22042213 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2213

Author(s):

Natalia Diaz-Garrido ◽

Cecilia Cordero ◽

Yenifer Olivo-Martinez ◽

Josefa Badia ◽

Laura Baldomà

Keyword(s):

Extracellular Vesicles ◽

Intestinal Mucosa ◽

Current Knowledge ◽

Cell Communication ◽

Bioactive Molecules ◽

Target Cells ◽

Immune Functions ◽

Intestinal Homeostasis ◽

General Terms ◽

Health And Disease

Communication between cells is crucial to preserve body homeostasis and health. Tightly controlled intercellular dialog is particularly relevant in the gut, where cells of the intestinal mucosa are constantly exposed to millions of microbes that have great impact on intestinal homeostasis by controlling barrier and immune functions. Recent knowledge involves extracellular vesicles (EVs) as mediators of such communication by transferring messenger bioactive molecules including proteins, lipids, and miRNAs between cells and tissues. The specific functions of EVs principally depend on the internal cargo, which upon delivery to target cells trigger signal events that modulate cellular functions. The vesicular cargo is greatly influenced by genetic, pathological, and environmental factors. This finding provides the basis for investigating potential clinical applications of EVs as therapeutic targets or diagnostic biomarkers. Here, we review current knowledge on the biogenesis and cargo composition of EVs in general terms. We then focus the attention to EVs released by cells of the intestinal mucosa and their impact on intestinal homeostasis in health and disease. We specifically highlight their role on epithelial barrier integrity, wound healing of epithelial cells, immunity, and microbiota shaping. Microbiota-derived EVs are not reviewed here.

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The Antiviral Properties of Cyclosporine. Focus on Coronavirus, Hepatitis C Virus, Influenza Virus, and Human Immunodeficiency Virus Infections

Biology ◽

10.3390/biology9080192 ◽

2020 ◽

Vol 9 (8) ◽

pp. 192 ◽

Cited By ~ 3

Author(s):

Paulina Glowacka ◽

Lidia Rudnicka ◽

Olga Warszawik-Hendzel ◽

Mariusz Sikora ◽

Mohamad Goldust ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Influenza Virus ◽

Hepatitis C ◽

Beneficial Effect ◽

Bacterial Infections ◽

Viral Infections ◽

Skin Diseases ◽

Current Knowledge ◽

Immunosuppressive Treatment ◽

Immunodeficiency Virus

This review updates current knowledge regarding the risk of viral infections, including COVID-19, in patients treated with cyclosporine. We also shortly refer to bacterial infections and parasitic infestations in patients treated with cyclosporin. Cyclosporine is an immunosuppressive drug, which is widely used in medicine, including in the treatment of autoimmune skin diseases in dermatology, rheumatology, ophthalmology and nephrology, and in organ transplantation. A usual concern associated with immunosuppressive treatment is the potential risk of infections. Interestingly, several data indicate a relatively low risk of infections, especially viral infections, in patients receiving cyclosporine. It was shown that cyclosporine exerts an inhibitory effect on the replication of some viruses, or may have a potentially beneficial effect on the disease course in infections. These include hepatitis C, influenza virus, rotavirus, human immunodeficiency virus and coronavirus infections. Available data indicate that cyclosporine may have a beneficial effect on COVID-19, which is caused by the coronavirus SARS-COV2.

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Biological role of zonulin: a biomarker of increased intestinal permeability syndrome

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-1-31-38 ◽

2021 ◽

Vol 66 (1) ◽

pp. 31-38

Author(s):

A. I. Khavkin ◽

N. M. Bogdanova ◽

V. P. Novikova

Keyword(s):

Digestive Tract ◽

Intestinal Microbiota ◽

Intestinal Mucosa ◽

Inflammatory Process ◽

Biological Rhythms ◽

Infectious Agent ◽

Biological Role ◽

Pathological Conditions ◽

Intercellular Connections

.Both changes in diet and pathological conditions caused by an infectious agent, allergic or autoimmune inflammatory process, affect the biological rhythms of the digestive tract, which negatively affects the intestinal microbiota and increases the permeability of the intestinal mucosa. The altered microbiota potentiates inflammation and causes a “vicious circle”. The zonulin protein is the agent that modulates the density of intercellular connections. The review presents data on the biological role of zonulin, correction of its synthesis violation with the help of functional products for baby food.

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Gut microbiome dysbiosis in anorexia nervosa

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0014.8601 ◽

2021 ◽

Vol 75 ◽

pp. 283-291

Author(s):

Agata Janczy ◽

Magdalena Landowska ◽

Zdzisław Kochan

Keyword(s):

Anorexia Nervosa ◽

Gut Microbiota ◽

Body Mass ◽

Intestinal Microbiota ◽

Gut Microbiome ◽

Dietary Habits ◽

Eating Habits ◽

Current Knowledge ◽

Functional Gastrointestinal Disorders

Anorexia nervosa (AN) is described as an eating disorder, which is characterized by malnutrition, a fear of gaining body mass, and a disturbed self-body image. This disease is dependent on biological, psychological and socio-cultural factors. Among the various biological factors, the importance of intestinal microbiota has recently attracted much attention. Identification of the gut microbiota dysbiosis in patients with AN has opened new and promising research directions. Recent observations focus in particular on the association between intestinal microorganisms and the occurrence of functional gastrointestinal disorders associated with anorexia, anxiety and depression, as well as the regulation of eating habits. The composition of the gut microbiota differs between patients with AN and individuals with normal body mass. This is due to the incorrect diet of patients; on the other hand, there is growing interest in the role of intestinal microbiota in the pathogenesis of AN, its changes through re-nutrition practices, and in particular the modulation of intestinal microbiological composition by means of nutritional interventions or the use of preand probiotics as standard supplements therapy of eating disorders. There is a need for further research about the microbiome - intestine - brain axis. Furthermore, consequences of changes in dietary habits as part of AN treatment are also unknown. However, better knowledge about the relationship between the gut microbiome and the brain can help improve the treatment of this disorder. This review aims to present the current knowledge about the potential role of intestinal microbiota in the pathogenesis, course and treatment of AN.

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Versatility of USP18 in physiology and pathophysiology

Acta Biochimica Polonica ◽

10.18388/abp.2019_2844 ◽

2019 ◽

Author(s):

Paulina Dziamałek-Macioszczyk ◽

Joanna Haraźna ◽

Tomasz Stompór

Keyword(s):

Bacterial Infections ◽

Current Knowledge ◽

Cell Signalling ◽

Signalling Pathways ◽

Type I ◽

Multifunctional Protein ◽

Enzymatic Function ◽

Multiple Processes ◽

Specific Protease ◽

Interferon Stimulated Gene 15

Ubiquitin-specific peptidase 18 (USP18) is a multifunctional protein and its roles are still being investigated. This enzyme removes ubiquitin-like molecules from their substrates and the only known interferon-stimulated gene 15 (ISG15) specific protease. Apart from its enzymatic function, it also inhibits interferon type I and III signalling pathways. USP18 is known to regulate multiple processes, such as: cell cycle, cell signalling and response to viral and bacterial infections. Moreover, it contributes to the development of several autoimmune diseases and carcinogenesis, and recently was described as a cardiac remodelling inhibitor. This review summarizes the current knowledge on USP18 functions, highlighting its contribution to the development of heart failure, given the fact that this disease’s etiology is now considered to be inflammatory in nature.

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