Login to your account
Don’t have an account?
Create a Free Account
Host-Microbiome Interactions
Modulation of Gut Microbiota Composition by Serotonin Signaling Influences Intestinal Immune Response and Susceptibility to Colitis
Serotonin (5-hydroxytryptamine [5-HT]) is synthesized mainly within enterochromaffin (EC) cells in the gut, and tryptophan hydroxylase 1 (Tph1) is the rate-limiting enzyme for 5-HT synthesis in EC cells. Accumulating evidence suggests the importance of gut microbiota in intestinal inflammation. Considering the close proximity of EC cells and the microbes, we investigated the influence of gut-derived 5-HT on the microbiota and the susceptibility to colitis.Plant-based Enteral Nutrition Modifies the Gut Microbiota and Improves Outcomes in Murine Models of Colitis
Exclusive enteral nutrition (EEN), ie, restricting patients to commercially available liquid diets with avoidance of solid food, is an effective treatment for Crohn’s disease (CD).1 However, commercial formulas used for EEN generally have low fiber and high sugar content and contain emulsifiers that worsen colitis in animal models.2 Despite its efficacy, EEN appears to accentuate microbial changes observed in CD, specifically a loss of protective anaerobes and the growth of pathogens.3 Plant-based enteral nutrition (PBEN) represents a high-fiber alternative to conventional enteral nutrition (CEN) without added sugar or artificial ingredients.Human Norovirus Propagation in Human Induced Pluripotent Stem Cell–Derived Intestinal Epithelial Cells
Worldwide, human norovirus (HuNoV) is a major cause of intestinal infectious gastroenteritis, leading to morbidity and mortality in children and the elderly, and it thus has major social and economic influences. Neither an effective vaccine nor an effective treatment is currently available. One of the biggest reasons for the lack of an appropriate prevention or treatment strategy is the unavailability of methods for culturing HuNoV. The recent development of a system of HuNoV replication in human primary intestinal epithelial cells (IECs) has spawned advances in HuNoV characterization and opened up new strategies for HuNoV vaccine development.Toll-Like Receptor 7 Agonist–Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells
Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS).Age-Related Changes in Gut Microbiota Alter Phenotype of Muscularis Macrophages and Disrupt Gastrointestinal Motility
Macrophages are classified as proinflammatory M1 (classically activated) or anti-inflammatory M2 (alternatively activated),1 but binary classification fails to distinguish macrophage expression profiles.2 Tissue resident muscularis macrophages (MMs) in the gut muscularis externa modulate gut homeostasis including neuromuscular function.3,4 Through neuroimmune cross-talk, MMs may sense cues in the microenvironment from the microbiota or extrinsic sympathetic neurons and relay this information to enteric neurons.Identification of Inner Mucus-Associated Bacteria by Laser Capture Microdissection
A primary means by which the intestine is protected against microbial onslaught is by production of a thick mucus gel that serves to physically separate the microbiota from epithelial cells. Accordingly, the outer regions of the mucus layer are heavily colonized by bacteria while the inner layer is nearly sterile.1 Alterations in intestinal microbiota composition are associated with various disease states, including inflammatory bowel disease, cancer, and metabolic syndrome. Although such associations generally have focused on the fecal microbiome, recent studies have highlighted the importance of mucosa-associated bacteria.Host-Gut Microbiota Crosstalk in Intestinal Adaptation
Short-bowel syndrome represents the most common cause of intestinal failure and occurs when the remaining intestine cannot support fluid and nutrient needs to sustain adequate physiology and development without the use of supplemental parenteral nutrition. After intestinal loss or damage, the remnant bowel undergoes multifactorial compensatory processes, termed adaptation, which are largely driven by intraluminal nutrient exposure. Previous studies have provided insight into the biological processes and mediators after resection, however, there still remains a gap in the knowledge of more comprehensive mechanisms that drive the adaptive responses in these patients.On and Off: A Dual Role for Cysteine Protease Autoprocessing of C difficile Toxin B on Cytotoxicity vs Proinflammatory Toxin Actions?
Clostridium difficile is the leading bacterial cause of health care–associated diarrhea in the developed world. In recent years, there has been an alarming increase in the incidence and severity of Clostridium difficile infections (CDIs), leading to increased academic, public health, and drug development research efforts on this bacterium. Two major virulence factors of C difficile are its toxin A (TcdA) and toxin B (TcdB). Understanding the mechanisms of action of these toxins is important to advance knowledge of CDI pathogenesis and identify new targets for prevention and therapy.Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC) remains the leading cause of death from gastrointestinal disease in premature infants and attacks the most fragile patients at a time when they appear to be the most stable. Despite significant advances in our overall care of the premature infant, NEC mortality remains stubbornly high. There is no specific treatment for NEC beyond broad-spectrum antibiotics and intestinal resection, and current efforts have focused on preventive strategies. Over the past decade, we have proposed a unifying hypothesis to explain the pathogenesis of NEC in premature infants that suggests that NEC develops in response to an imbalance between exaggerated proinflammatory signaling in the mucosa of the premature gut leading to mucosal injury, which is not countered effectively by endogenous repair processes, and in the setting of impaired mesenteric perfusion leads to intestinal ischemia and disease development.The Brain-Gut-Microbiome Axis
Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression.Enteropathogenic Escherichia coli EspH-Mediated Rho GTPase Inhibition Results in Desmosomal Perturbations
The diarrheagenic pathogen, enteropathogenic Escherichia coli (EPEC), uses a type III secretion system to deliver effector molecules into intestinal epithelial cells (IECs). While exploring the basis for the lateral membrane separation of EPEC-infected IECs, we observed infection-induced loss of the desmosomal cadherin desmoglein-2 (DSG2). We sought to identify the molecule(s) involved in, and delineate the mechanisms and consequences of, EPEC-induced DSG2 loss.Attaching-and-Effacing Pathogens Exploit Junction Regulatory Activities of N-WASP and SNX9 to Disrupt the Intestinal Barrier
Neural Wiskott-Aldrich Syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton in epithelial tissues and is poised to mediate cytoskeletal-dependent aspects of apical junction complex (AJC) homeostasis. Attaching-and-effacing (AE) pathogens disrupt this homeostasis through translocation of the effector molecule early secreted antigenic target-6 (ESX)-1 secretion-associated protein F (EspF). Although the mechanisms underlying AJC disruption by EspF are unknown, EspF contains putative binding sites for N-WASP and the endocytic regulator sorting nexin 9 (SNX9).Antibiotic Treatment Leads to Fecal Escherichia coli and Coliphage Expansion in Severely Malnourished Diarrhea Patients
Malnutrition predisposes to diarrhea and diarrhea adversely affects the nutritional status creating a vicious cycle.1 The role of the gut microbiome in malnutrition is an active research area.2 Parenteral antibiotics are recommended by the World Health Organization in hospitalized pediatric patients with severe acute malnutrition (SAM) presenting signs of infections.3 Stool microbiota data for such patients are, however, lacking. To fill this gap, we studied the stool microbiota in 19 SAM patients from Bangladesh hospitalized with acute diarrhea (AD) and compared it with that of matched 20 healthy control subjects (HC) (Supplementary Table 1).Engineered Human Gastrointestinal Cultures to Study the Microbiome and Infectious Diseases
New models to study the intestine are key to understanding intestinal diseases and developing novel treatments. Intestinal organ-like culture systems (organoids and enteroids) have substantially advanced the study of the human gastrointestinal tract. Stem cell–derived cultures produce self-organizing structures that contain the multiple differentiated intestinal epithelial cell types including enterocytes, goblet, Paneth, and enteroendocrine cells. Understanding host–microbial interactions is one area in which these cultures are expediting major advancements.Tightening the Case for Gut Microbiota in Autism-Spectrum Disorder
Autism-spectrum disorder (ASD) is a developmental behavioral disorder often accompanied and aggravated by a range of gastrointestinal and cognitive dysfunction. The concern for ASD reflects its increasing incidence and the disproportionate burden of this and other cognitive disorders on those affected and the family and community around them. Is there a role for us to help from the distant fields of gastroenterology and hepatology?Gastrointestinal Organoids: Understanding the Molecular Basis of the Host–Microbe Interface
In recent years, increasing attention has been devoted to the concept that microorganisms play an integral role in human physiology and pathophysiology. Despite this, the molecular basis of host–pathogen and host–symbiont interactions in the human intestine remains poorly understood owing to the limited availability of human tissue, and the biological complexity of host–microbe interactions. Over the past decade, technological advances have enabled long-term culture of organotypic intestinal tissue derived from human subjects and from human pluripotent stem cells, and these in vitro culture systems already have shown the potential to inform our understanding significantly of host-microbe interactions.Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder
Emerging data on the gut microbiome in autism spectrum disorder (ASD) suggest that altered host–microbe interactions may contribute to disease symptoms. Although gut microbial communities in children with ASD are reported to differ from individuals with neurotypical development, it is not known whether these bacteria induce pathogenic neuroimmune signals.Disease-Associated Microbial Communities in Healthy Relatives: A Bacteria-Filled Crystal Ball?
The bacterial community within the gastrointestinal tract has been the subject of a great deal of investigation as well as a great deal of press. Numerous studies have shown that inflammatory bowel disease (IBD) is associated with an alteration in the ecological system within our gut,1 and findings from mouse models suggest that inflammation-associated microbiota transplanted from human IBD patients can contribute actively to colitis.2 Still, it is not clear whether dysbiosis is either necessary or sufficient as an initiating event—especially in human beings—or if in contrast only a microbiome that already has been shaped by the inflammatory state is able to contribute further to disease.Zooming in on Inflammatory Bowel Disease: Microbial and Proteomic Features Associated With IBD in Colonic Microenvironments
Inflammatory bowel disease (IBD) is a multifactorial chronic intestinal inflammatory disorder characterized both by genetic and environmental factors.1 Among the latter, the microbiome recently emerged as one of the most promising avenues of research to understand the pathogenesis of IBD. Several studies have shown differences in microbiome composition and diversity in IBD patients compared with healthy controls.2,3 Larger cohorts have allowed for further characterization of the gut microbiota in IBD patients, including assays that determine function and activity of the microbiome and thus provide better mechanistic insights.A Disease-Associated Microbial and Metabolomics State in Relatives of Pediatric Inflammatory Bowel Disease Patients
Microbes may increase susceptibility to inflammatory bowel disease (IBD) by producing bioactive metabolites that affect immune activity and epithelial function. We undertook a family based study to identify microbial and metabolic features of IBD that may represent a predisease risk state when found in healthy first-degree relatives.Metagenomic Characterization of Microbial Communities In Situ Within the Deeper Layers of the Ileum in Crohn’s Disease
Microbial dysbiosis and aberrant host–microbe interactions in the gut are believed to contribute to the development and progression of Crohn’s disease (CD). Microbiome studies in CD typically have focused on microbiota in feces or superficial mucosal layers of the colon because accessing DNA from deeper layers of the bowel is challenging. In this study, we analyzed the deep tissue microbiome in patients who underwent surgical resection of the small intestine.Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel Disease
Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosal–luminal interface to study the disease-related biology of the human colonic mucosa.Microbiota Alterations in Inflammatory Bowel Diseases: From Correlation to Causality
Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders, mainly comprising Crohn’s disease (CD) and ulcerative colitis, which together affect 1.4 million people in the United States and 2.2 million people in Europe.1 Many studies have shown the presence of an altered intestinal microbiota composition in IBD patients, as well as in mouse models of chronic intestinal inflammation (such as Toll-like receptor 5-/- and interleukin 10-/- models).2–6 However, as stated by the authors of an exciting article published in the current issue of Cellular and Molecular Gastroenterology and Hepatology, “it remains unclear whether IBD-associated gut dysbiosis contributes to disease pathogenesis or is merely secondary to intestinal inflammation.”7 Although many studies have described alterations of microbiota composition, localization, transcriptome, and/or proinflammatory potential during intestinal inflammation, these observations could be consecutive to the intestinal inflammation instead of being a primary causative hit that contributes to the appearance of inflammation.The Pathogenesis of Resection-Associated Intestinal Adaptation
After massive small-bowel resection, the remnant bowel compensates by a process termed adaptation. Adaptation is characterized by villus elongation and crypt deepening, which increases the capacity for absorption and digestion per unit length. The mechanisms/mediators of this important response are multiple. The purpose of this review is to highlight the major basic contributions in elucidating a more comprehensive understanding of this process.Putting the Pieces Together: NOD-Like Receptor Protein 3 Inflammasome Priming and Activation in Barrett's Epithelial Cells
After insults such as injury caused by gastrointestinal reflux, the stratified squamous epithelium of the esophagus is replaced with glandular mucosa (Barrett’s esophagus), which can be a mosaic of metaplastic columnar intestinal-like or gastric-like epithelium.1 This Barrett’s epithelium shows altered differentiation and is characterized morphologically by a sequence of dysplasia, from low-grade to high-grade and intestinal metaplasia, which ultimately may evolve to invasive cancer.
Copyright © 2023 Elsevier Inc. except certain content provided by third parties. The content on this site is intended for healthcare professionals.
