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.

Biomarkers of pain in infants and children

2021 ◽  
pp. 412-421
Author(s):  
Naama Rotem-Kohavi ◽  
Susanne Brummelte ◽  
Kenneth D. Craig ◽  
Tim F. Oberlander
Keyword(s):  
Stress Reactivity ◽  
Life Experience ◽  
Physiological Stress ◽  
Clinical Care ◽  
Infants And Children ◽  
Developmental Changes ◽  
Motor Disabilities ◽  
Reflecting Function ◽  
Health And Disease ◽  
In Infants And Children

Biomarkers are commonly used in clinical care and research as indicators of diseases and physiological states. Preferably, a biomarker should be readily accessible, low in cost, easy to interpret, highly specific, and sensitive to health and disease. Owing to the complexity of the pain system, no unidimensional reliable biomarker for pain has been identified that meets all of these criteria to date. In children, neurologically dependent developmental changes, maturation of physiological stress reactivity systems, and life experience add additional layers of complexity to the use of biomarkers of pain. Nevertheless, readily available and reliable biomarkers reflecting function of the pain system would greatly enhance timely and appropriate understanding and treatment of pain, especially in infants and children with communication, cognitive, and motor disabilities. This chapter examines currently available pain-related biomarkers, their use, and limitations.

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 Systems Biology and Kidney Disease

2020 ◽  
Vol 15 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Jennifer A. Schaub ◽  
Habib Hamidi ◽  
Lalita Subramanian ◽  
Matthias Kretzler
Keyword(s):  
Systems Biology ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Clinical Care ◽  
Treatment Options ◽  
Cell Types ◽  
Current State ◽  
Health And Disease ◽  
National Databases ◽  
Different Cell Types

The kidney is a complex organ responsible for maintaining multiple aspects of homeostasis in the human body. The combination of distinct, yet interrelated, molecular functions across different cell types make the delineation of factors associated with loss or decline in kidney function challenging. Consequently, there has been a paucity of new diagnostic markers and treatment options becoming available to clinicians and patients in managing kidney diseases. A systems biology approach to understanding the kidney leverages recent advances in computational technology and methods to integrate diverse sets of data. It has the potential to unravel the interplay of multiple genes, proteins, and molecular mechanisms that drive key functions in kidney health and disease. The emergence of large, detailed, multilevel biologic and clinical data from national databases, cohort studies, and trials now provide the critical pieces needed for meaningful application of systems biology approaches in nephrology. The purpose of this review is to provide an overview of the current state in the evolution of the field. Recent successes of systems biology to identify targeted therapies linked to mechanistic biomarkers in the kidney are described to emphasize the relevance to clinical care and the outlook for improving outcomes for patients with kidney diseases.

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 16S rRNA sequencing of samples from universal stool bank donors

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Marina Santiago ◽  
Scott W. Olesen
Keyword(s):  
Microbial Community ◽  
16S Rrna ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
16S Rrna Sequencing ◽  
Clostridioides Difficile ◽  
Rrna Sequencing ◽  
Health And Disease ◽  
Gut Microbial Community ◽  
Stool Bank

Abstract Objectives Universal stool banks provide stool to physicians for use in treating recurrent Clostridioides difficile infection via fecal microbiota transplantation. Stool donors providing the material are rigorously screened for diseases and disorders with a potential microbiome etiology, and they are likely healthier than the controls in most microbiome datasets. 16S rRNA sequencing was performed on samples from a selection of stool donors at a large stool bank, OpenBiome, to characterize their gut microbial community and to compare samples across different timepoints and sequencing runs. Data description 16S rRNA sequencing was performed on 200 samples derived from 170 unique stool donations from 86 unique donors. Samples were sequenced on 11 different sequencing runs. We are making this data available because rigorously screened, likely very healthy stool donors may be useful for characterizing and understanding microbial community differences across different populations and will help shed light into the how the microbiome community promotes health and disease.

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.

Pyloric distensibility in health and disease

2021 ◽  
Author(s):  
Fabien Wuestenberghs ◽  
Guillaume Gourcerol
Keyword(s):  
Gastric Emptying ◽  
Clinical Care ◽  
Botulinum Toxin Injection ◽  
Gastric Volume ◽  
Imaging Studies ◽  
Endoscopic Techniques ◽  
3 Dimensional ◽  
Routine Clinical Care ◽  
Health And Disease ◽  
Per Oral

Until recently, gastric motility measurements in Humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and gastric emptying tests, the latter being the only one performed in routine clinical care. Accurate and easy to use techniques were lacking to assess pyloric function in health and disease. Recently, pyloric distensibility has been developed and validated to assess pyloric opening. Several studies confirmed that pyloric distensibility was decreased in gastroparesis and correlated with gastric emptying as well as gastroparesis symptoms. In addition, pyloric distensibility may predict outcome of endoscopic techniques targeting the pylorus, namely intra-pyloric botulinum toxin injection and gastric per-oral pyloromyotomy. Pyloric distensibility appears therefore to be a promising and useful new tool in the workup of gastroparesis patients.

scholarly journals Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes

2020 ◽  
Author(s):  
Teruyuki Sano ◽  
Takahiro Kageyama ◽  
Victoria Fang ◽  
Ranit Kedmi ◽  
Jhimmy Talbot ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lymph Nodes ◽  
Lamina Propria ◽  
Th17 Cell ◽  
Mucosal Barrier ◽  
T Helper ◽  
Mesenteric Lymph Nodes ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
Draining Lymph Nodes

SummaryDifferentiation of intestinal T helper 17 (Th17) cells, which contribute to mucosal barrier protection from invasive pathogens, is dependent on colonization with distinct commensal bacteria. Segmented filamentous bacteria (SFB) are sufficient to support Th17 cell differentiation in mouse, but the molecular and cellular requirements for this process remain incompletely characterized. Here we show that intestine-draining mesenteric lymph nodes (MLN) are the dominant site of SFB-induced intestinal Th17 cell differentiation. Subsequent migration of these cells to the intestinal lamina propria is dependent on their up-regulation of integrin β7. Stat3-dependent induction of RORγt, the Th17 cell-specifying transcription factor, largely depends on IL-6, but signaling through the receptors for IL-21 and IL-23 can compensate for absence of IL-6 to promote SFB-directed Th17 cell differentiation. These results indicate that redundant cytokine signals guide commensal microbe-dependent Th17 cell differentiation in the MLN and accumulation of the cells in the lamina propria.

The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock

2006 ◽  
Vol 291 (4) ◽  
pp. G556-G565 ◽  
Author(s):  
Kathleen G. Raman ◽  
Penny L. Sappington ◽  
Runkuan Yang ◽  
Ryan M. Levy ◽  
Jose M. Prince ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
High Plasma ◽  
Mucosal Barrier ◽  
Barrier Dysfunction ◽  
Mesenteric Lymph Nodes ◽  
Mucosal Permeability ◽  
Intestinal Barrier Dysfunction ◽  
Soluble Rage

The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of numerous conditions associated with excessive inflammation. To determine whether RAGE-dependent signaling is important in the development of intestinal barrier dysfunction after hemorrhagic shock and resuscitation (HS/R), C57Bl/6, rage−/−, or congenic rage+/+ mice were subjected to HS/R (mean arterial pressure of 25 mmHg for 3 h) or a sham procedure. Twenty-four hours later, bacterial translocation to mesenteric lymph nodes and ileal mucosal permeability to FITC-labeled dextran were assessed. Additionally, samples of ileum were obtained for immunofluorescence microscopy, and plasma was collected for measuring IL-6 and IL-10 levels. HS/R in C57Bl/6 mice was associated with increased bacterial translocation, ileal mucosal hyperpermeability, and high circulating levels of IL-6. All of these effects were prevented when C57Bl/6 mice were treated with recombinant human soluble RAGE (sRAGE; the extracellular ligand-binding domain of RAGE). HS/R induced bacterial translocation, ileal mucosal hyperpermeability, and high plasma IL-6 levels in rage+/+ but not rage−/− mice. Circulating IL-10 levels were higher in rage−/− compared with rage+/+ mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R.

scholarly journals A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice

Gut ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 1988-1997 ◽  
Author(s):  
Lijuan Wang ◽  
Lei Tang ◽  
Yiming Feng ◽  
Suying Zhao ◽  
Mei Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Membrane Protein ◽  
Causative Role ◽  
Mesenteric Lymph Nodes ◽  
Akkermansia Muciniphila ◽  
Tnf Α ◽  
Rrna Sequencing ◽  
Inflammatory Bowel ◽  
Cell Conditioned Medium

ObjectiveGut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). Akkermansia muciniphila (A. muciniphila) is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates how A. muciniphila engages the immune response in CAC.DesignMice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised A. muciniphila or a specific outer membrane protein (Amuc_1100) treatment. Faeces from mice and patients with IBD or CRC were collected for 16S rRNA sequencing. The effects of A. muciniphila or Amuc_1100 on the immune response in acute colitis and CAC were investigated.ResultsA. muciniphila was significantly reduced in patients with IBD and mice with colitis or CAC. A. muciniphila or Amuc_1100 could improve colitis, with a reduction in infiltrating macrophages and CD8+ cytotoxic T lymphocytes (CTLs) in the colon. Their treatment also decreased CD16/32+ macrophages in the spleen and mesenteric lymph nodes (MLN) of colitis mice. Amuc_1100 elevated PD-1+ CTLs in the spleen. Moreover, A. muciniphila and Amuc_1100 blunted tumourigenesis by expanding CTLs in the colon and MLN. Remarkably, they activated CTLs in the MLN, as indicated by TNF-α induction and PD-1downregulation. Amuc_1100 could stimulate and activate CTLs from splenocytes in CT26 cell conditioned medium.ConclusionsThese data indicate that pasteurised A. muciniphila or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.

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