The esophageal mucosal barrier in health and disease: mucosal pathophysiology and protective mechanisms

2020 ◽  
Vol 1482 (1) ◽  
pp. 49-60
Author(s):  
C. Prakash Gyawali ◽  
Irene Sonu ◽  
Laren Becker ◽  
Jerzy Sarosiek
Keyword(s):  
Mucosal Barrier ◽  
Protective Mechanisms ◽  
Health And Disease

scholarly journals The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human

2018 ◽  
Vol 6 (3) ◽  
pp. 78 ◽  
Author(s):  
Anthony P. Corfield
Keyword(s):  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Mucosal Barrier ◽  
High Carbohydrate ◽  
Mucosal Surfaces ◽  
Wide Range ◽  
Health And Disease ◽  
Mucus Barrier ◽  
Gel Barrier ◽  
Mucus Glycoproteins

Glycoproteins are major players in the mucus protective barrier in the gastrointestinal and other mucosal surfaces. In particular the mucus glycoproteins, or mucins, are responsible for the protective gel barrier. They are characterized by their high carbohydrate content, present in their variable number, tandem repeat domains. Throughout evolution the mucins have been maintained as integral components of the mucosal barrier, emphasizing their essential biological status. The glycosylation of the mucins is achieved through a series of biosynthetic pathways processes, which generate the wide range of glycans found in these molecules. Thus mucins are decorated with molecules having information in the form of a glycocode. The enteric microbiota interacts with the mucosal mucus barrier in a variety of ways in order to fulfill its many normal processes. How bacteria read the glycocode and link to normal and pathological processes is outlined in the review.

scholarly journals The importance of intestinal microbiota and its role in the nosocomial infection

2021 ◽  
Vol 10 (10) ◽  
pp. e489101019166 ◽  
Author(s):  
Luisa Ferreira da Cruz ◽  
Israel Lucas Antunes Souza ◽  
Larissa Dias de Souza ◽  
Marcelo Gonzaga de Freitas Araújo ◽  
Paulo Afonso Granjeiro
Keyword(s):  
Nosocomial Infection ◽  
Intestinal Microbiota ◽  
Nosocomial Infections ◽  
Bacterial Colonization ◽  
Intestinal Wall ◽  
Mucosal Barrier ◽  
Microbial Composition ◽  
Metabolic Functions ◽  
Mucosal Barrier Function ◽  
Health And Disease

The gastrointestinal tract houses the largest and most complex community of microorganisms, and this bacterial colonization of the human intestine by environmental microbes begins immediately after the birth. The intestinal microbiota has several important and unique functions, including metabolic functions such as the biotransformation of drugs and the digestion of dietary compounds; a mucosal barrier function by inhibiting the invasion of pathogens and an immunomodulatory function. On the other hand, some commensal bacteria can be pathogenic, causing infections if the natural host is compromised and, in predisposed hosts, the intestinal microbiota can be involved in nosocomial infection. The translocation of bacteria through the intestinal wall is considered one of the main causes of nosocomial infections. The aim of this review is to provide a comprehensive view of the human gut microbiota, its main functions, its role in health and disease, addressing the correlation between intestinal microbial composition and nosocomial infections.

scholarly journals Airway Smooth Muscle Dynamics and Hyperresponsiveness: In and outside the Clinic

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Peter B. Noble ◽  
Thomas K. Ansell ◽  
Alan L. James ◽  
Peter K. McFawn ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Lung Function ◽  
Airway Smooth Muscle ◽  
Underlying Mechanism ◽  
Protective Mechanisms ◽  
Functional Abnormality ◽  
Airway Narrowing ◽  
Asthmatic Patients ◽  
Muscle Dynamics ◽  
Health And Disease

The primary functional abnormality in asthma is airway hyperresponsiveness (AHR)—excessive airway narrowing to bronchoconstrictor stimuli. Our understanding of the underlying mechanism(s) producing AHR is incomplete. While structure-function relationships have been evoked to explain AHR (e.g., increased airway smooth muscle (ASM) mass in asthma) more recently there has been a focus on how the dynamic mechanical environment of the lung impacts airway responsiveness in health and disease. The effects of breathing movements such as deep inspiration reveal innate protective mechanisms in healthy individuals that are likely mediated by dynamic ASM stretch but which may be impaired in asthmatic patients and thereby facilitate AHR. This perspective considers the evidence for and against a role of dynamic ASM stretch in limiting the capacity of airways to narrow excessively. We propose that lung function measured after bronchial provocation in the laboratory and changes in lung function perceived by the patient in everyday life may be quite different in their dependence on dynamic ASM stretch.

scholarly journals Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts

2003 ◽  
Vol 6 (1) ◽  
pp. 6-23 ◽  
Author(s):  
Wei Hsueh ◽  
Michael S. Caplan ◽  
Xiao-Wu Qu ◽  
Xiao-Di Tan ◽  
Isabelle G. De Plaen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Necrotizing Enterocolitis ◽  
Enteral Feeding ◽  
Tissue Injury ◽  
Experimental Models ◽  
Mucosal Barrier ◽  
Protective Mechanisms ◽  
Adult Rats ◽  
Intestinal Necrosis ◽  
Proinflammatory Mediators

Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-α (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms.

scholarly journals Early Microbial–Immune Interactions and Innate Immune Training of the Respiratory System during Health and Disease

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 413
Author(s):  
Gustavo Nino ◽  
Carlos E. Rodriguez-Martinez ◽  
Maria J. Gutierrez
Keyword(s):  
Respiratory System ◽  
Early Life ◽  
Respiratory Infections ◽  
Bacterial Colonization ◽  
Innate Immune ◽  
Mucosal Barrier ◽  
Birth Cohorts ◽  
Immune Development ◽  
Key Factor ◽  
Health And Disease

Over the past two decades, several studies have positioned early-life microbial exposure as a key factor for protection or susceptibility to respiratory diseases. Birth cohorts have identified a strong link between neonatal bacterial colonization of the nasal airway and gut with the risk for respiratory infections and childhood asthma. Translational studies have provided companion mechanistic insights on how viral and bacterial exposures in early life affect immune development at the respiratory mucosal barrier. In this review, we summarize and discuss our current understanding of how early microbial–immune interactions occur during infancy, with a particular focus on the emergent paradigm of “innate immune training”. Future human-based studies including newborns and infants are needed to inform the timing and key pathways implicated in the development, maturation, and innate training of the airway immune response, and how early microbiota and virus exposures modulate these processes in the respiratory system during health and disease.

scholarly journals Primary human colonic mucosal barrier crosstalk with super oxygen-sensitive Faecalibacterium prausnitzii in continuous culture

2020 ◽  
Author(s):  
Jianbo Zhang ◽  
Yu-Ja Huang ◽  
Jun-Young Yoon ◽  
John Kemmitt ◽  
Charles Wright ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Mucosal Barrier ◽  
Strictly Anaerobic ◽  
Clinical Observations ◽  
Faecalibacterium Prausnitzii ◽  
Oxygen Sensitive ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Anti Inflammatory

AbstractThe gut microbiome plays an important role in human health and disease. Gnotobiotic animal and in vitro cell-based models provide some informative insights into mechanistic crosstalk. However, there is no existing system for a chronic co-culture of a human colonic mucosal barrier with super oxygen-sensitive commensal microbes, hindering the study of human-microbe interactions in a controlled manner. Here, we investigated the effects of an abundant super oxygen-sensitive commensal anaerobe, Faecalibacterium prausnitzii, on a primary human mucosal barrier using a Gut-MIcrobiome (GuMI) physiome platform that we designed and fabricated. Chronic continuous co-culture of F. prausnitzii for two days with colon epithelia, enabled by continuous flow of completely anoxic apical media and aerobic basal media, resulted in a strictly anaerobic apical environment fostering growth of and butyrate production by F. prausnitzii, while maintaining a stable colon epithelial barrier. We identified elevated differentiation and hypoxia-responsive genes and pathways in the platform compared with conventional aerobic static culture of the colon epithelia, attributable to a combination of anaerobic environment and continuous medium replenishment. Furthermore, we demonstrated anti-inflammatory effects of F. prausnitzii through HDAC and the TLR-NFKB axis. Finally, we identified that butyrate largely contributes to the anti-inflammatory effects by downregulating TLR3 and TLR4. Our results are consistent with some clinical observations regarding F. prausnitzii, thus motivating further studies employing this platform with more complex engineered colon tissues for understanding the interaction between the human colonic mucosal barrier and microbiota, pathogens, or engineered bacteria.

scholarly journals Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1283
Author(s):  
Larry D. Sanford ◽  
Laurie L. Wellman ◽  
Richard P. Ciavarra ◽  
Edward C. Oldfield ◽  
Rouzbeh Shams ◽  
...  
Keyword(s):  
Clinical Care ◽  
Sleep Fragmentation ◽  
Brain Inflammation ◽  
Mucosal Barrier ◽  
Mesenteric Lymph Nodes ◽  
Rrna Sequencing ◽  
Health And Disease ◽  
Marked Suppression ◽  
Receptor Ccr5 ◽  
Effect Of Light

Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axis. Male C57BL/6NCrl mice (4 to 5 per cage, fed standard lab chow) experienced SF via mechanical stimulation at 2 min intervals during the light (SF) and dark (DD, dark disturbances) periods. Home cage (HC) controls were undisturbed. After 10 days, fecal samples were collected at light onset, midday, light offset, and midnight. Samples were also collected after 10 days without SF. Subsequently, the mice were randomized across groups and allowed 20 additional days of recovery followed by 10 days of SF or DD. To assess effects on the microbiota, 16S rRNA sequencing was used, and mesenteric lymph nodes (MLNs) and cortex and medial prefrontal cortex were analyzed using cytokine arrays. SF and DD produced significant alterations in the microbiota compared to HC, and DD had greater impact than SF on some organisms. SF produced marked suppression in MLNs of chemokines that regulate inflammation (CCL3, CCL4 and their receptor CCR5) and maintain the immune mucosal barrier (Cxcl13) at the same time that cortical cytokines (IL-33) indicated neuroinflammation. DD effects on immune responses were similar to HC. These data suggest that SF alters the microbiome and suppresses mucosal immunity at the same time that mediators of brain inflammation are upregulated. The translational implications for potential application to clinical care are compelling.

Drug Induced Changes in Cell Organelles

1968 ◽  
Vol 26 ◽  
pp. 110-111
Author(s):  
Sarah A. Luse
Keyword(s):  
Clinical Medicine ◽  
Cell Organelles ◽  
Riboflavin Deficiency ◽  
Drug Induced ◽  
New Era ◽  
Health And Disease ◽  
In The Beginning ◽  
Cellular Pathology ◽  
Induced Changes ◽  
The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

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