scholarly journals Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

2017 ◽  
Author(s):  
David R. Hill ◽  
Sha Huang ◽  
Melinda S. Nagy ◽  
Veda K. Yadagiri ◽  
Courtney Fields ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Microbial Colonization ◽  
Human Pluripotent Stem Cell ◽  
Complex Environment ◽  
Human Gastrointestinal Tract ◽  
Oral Nutrition ◽  
Host Interactions ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Intestinal Epithelium

AbstractThe human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is diZcult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naïve epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

scholarly journals Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
David R Hill ◽  
Sha Huang ◽  
Melinda S Nagy ◽  
Veda K Yadagiri ◽  
Courtney Fields ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Microbial Colonization ◽  
Human Pluripotent Stem Cell ◽  
Complex Environment ◽  
Human Gastrointestinal Tract ◽  
Oral Nutrition ◽  
Host Interactions ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Intestinal Epithelium

The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

scholarly journals Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 999
Author(s):  
Sue E. Crawford ◽  
Sasirekha Ramani ◽  
Sarah E. Blutt ◽  
Mary K. Estes
Keyword(s):  
Cell Types ◽  
Human Infection ◽  
Viral Pathogens ◽  
Host Interactions ◽  
Complex Interactions ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Intestinal Epithelium ◽  
Human Viruses ◽  
Human Infections

Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.

scholarly journals Mucosal microbial parasites/symbionts in health and disease: an integrative overview

Parasitology ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. 1109-1115 ◽  
Author(s):  
Robert P. Hirt
Keyword(s):  
Host Interactions ◽  
Detection Techniques ◽  
Symbiotic Relationships ◽  
Life Styles ◽  
Mucosal Surfaces ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions ◽  
Species Being

AbstractMicrobial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host–parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites–microbiota–host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host–microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host–microbe interactions in both human health and disease.

scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

scholarly journals Gut Microbiota and Iron: The Crucial Actors in Health and Disease

2018 ◽  
Vol 11 (4) ◽  
pp. 98 ◽  
Author(s):  
Bahtiyar Yilmaz ◽  
Hai Li
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Life Forms ◽  
Iron Availability ◽  
Human Beings ◽  
Human Gastrointestinal Tract ◽  
Dynamic Modulation ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions

Iron (Fe) is a highly ample metal on planet earth (~35% of the Earth’s mass) and is particularly essential for most life forms, including from bacteria to mammals. Nonetheless, iron deficiency is highly prevalent in developing countries, and oral administration of this metal is so far the most effective treatment for human beings. Notably, the excessive amount of unabsorbed iron leave unappreciated side effects at the highly interactive host–microbe interface of the human gastrointestinal tract. Recent advances in elucidating the molecular basis of interactions between iron and gut microbiota shed new light(s) on the health and pathogenesis of intestinal inflammatory diseases. We here aim to present the dynamic modulation of intestinal microbiota by iron availability, and conversely, the influence on dietary iron absorption in the gut. The central part of this review is intended to summarize our current understanding about the effects of luminal iron on host–microbe interactions in the context of human health and disease.

scholarly journals Identification of Biomarkers for Systemic Distribution of Nanovesicles From Lactobacillus johnsonii N6.2

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalie A. Harrison ◽  
Christopher L. Gardner ◽  
Danilo R. da Silva ◽  
Claudio F. Gonzalez ◽  
Graciela L. Lorca
Keyword(s):  
Immune Modulation ◽  
Lactobacillus Johnsonii ◽  
Immunogold Staining ◽  
Intracellular Space ◽  
Host Interactions ◽  
Systemic Distribution ◽  
Significant Enrichment ◽  
Microbe Interactions ◽  
Host Microbe Interactions

The ability of bacterial extracellular vesicles (EV) to transport biological molecules has increased the research to determine their potential as therapeutic agents. In this study, Lactobacillus johnsonii N6.2-derived nanovesicles (NV) were characterized to identify components that may serve as biomarkers in host-microbe interactions. Comparative proteomic and lipidomic analyses of L. johnsonii N6.2 NV and cell membrane (CM) were performed. The lipidomic profiles indicated that both fractions contained similar lipids, however, significant differences were observed in several classes. LC-MS/MS proteomic analysis indicated that NV contained several unique and differentially expressed proteins when compared to the CM. Analysis of Gene Ontology (GO) terms, based on cellular component, showed significant enrichment of proteins in the cytoplasm/intracellular space category for the NV fraction. Based on these results, the proteins T285_RS00825 (named Sdp), Eno3 and LexA were selected for studies of localization and as potential biomarkers for host-microbe interactions. Immunogold staining, followed by scanning and transmission electron microscopy (SEM and TEM, respectively), revealed that Sdp was preferentially localized along the cell wall/membrane, and on NV-like structures surrounding the bacteria. These results were confirmed using immunofluorescence staining in Caco-2 cells incubated with NV. Consequently, we evaluated the potential for NV surface-exposed proteins to generate an immune response in the host. Plasma from individuals administered L. johnsonii N6.2 showed that IgA and IgG antibodies were generated against NV and Sdp domains in vivo. Altogether, these results show that L. johnsonii N6.2 NV have the potential to mediate host interactions through immune modulation.

scholarly journals Functions of Sphingolipids in Pathogenesis During Host–Pathogen Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Wang ◽  
Yi-Li Chen ◽  
Yong-Kang Li ◽  
Ding-Kang Chen ◽  
Jia-Fan He ◽  
...  
Keyword(s):  
Membrane Lipids ◽  
Host Factors ◽  
Bioactive Molecules ◽  
Microbial Pathogens ◽  
Microbial Pathogenesis ◽  
Host Interactions ◽  
Current State ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Host Metabolism

Sphingolipids are a class of membrane lipids that serve as vital structural and signaling bioactive molecules in organisms ranging from yeast to animals. Recent studies have emphasized the importance of sphingolipids as signaling molecules in the development and pathogenicity of microbial pathogens including bacteria, fungi, and viruses. In particular, sphingolipids play key roles in regulating the delicate balance between microbes and hosts during microbial pathogenesis. Some pathogens, such as bacteria and viruses, harness host sphingolipids to promote development and infection, whereas sphingolipids from both the host and pathogen are involved in fungus–host interactions. Moreover, a regulatory role for sphingolipids has been described, but their effects on host physiology and metabolism remain to be elucidated. Here, we summarize the current state of knowledge about the roles of sphingolipids in pathogenesis and interactions with host factors, including how sphingolipids modify pathogen and host metabolism with a focus on pathogenesis regulators and relevant metabolic enzymes. In addition, we discuss emerging perspectives on targeting sphingolipids that function in host–microbe interactions as new therapeutic strategies for infectious diseases.

scholarly journals Xenorhabdus nematophilus as a Model for Host-Bacterium Interactions: rpoS Is Necessary for Mutualism with Nematodes

2001 ◽  
Vol 183 (16) ◽  
pp. 4687-4693 ◽  
Author(s):  
Eugenio I. Vivas ◽  
Heidi Goodrich-Blair
Keyword(s):  
Molecular Mechanisms ◽  
Host Bacterium ◽  
Gram Negative ◽  
Host Interactions ◽  
Specific Allele ◽  
Microbe Interactions ◽  
Xenorhabdus Nematophilus ◽  
Host Microbe Interactions ◽  
Wild Type Parent

ABSTRACT Xenorhabdus nematophilus, a gram-negative bacterium, is a mutualist of Steinernema carpocapsae nematodes and a pathogen of larval-stage insects. We use this organism as a model of host-microbe interactions to identify the functions bacteria require for mutualism, pathogenesis, or both. In many gram-negative bacteria, the transcription factor ςS controls regulons that can mediate stress resistance, survival, or host interactions. Therefore, we examined the role of ςS in the ability of X. nematophilus to interact with its hosts. We cloned, sequenced, and disrupted the X. nematophilus rpoS gene that encodes ςS. The X. nematophilus rpoS mutant pathogenized insects as well as its wild-type parent. However, therpoS mutant could not mutualistically colonize nematode intestines. To our knowledge, this is the first report of a specific allele that affects the ability of X. nematophilus to exist within nematode intestines, an important step in understanding the molecular mechanisms of this association.

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