Fucose Ameliorates Tritrichomonas sp.-Associated Illness in Antibiotic-Treated Muc2−/− Mice

The mucus layer in the intestine plays a critical role in regulation of host–microbe interactions and maintaining homeostasis. Disruptions of the mucus layer due to genetic, environmental, or immune factors may lead to inflammatory bowel diseases (IBD). IBD frequently are accompanied with infections, and therefore are treated with antibiotics. Hence, it is important to evaluate risks of antibiotic treatment in individuals with vulnerable gut barrier and chronic inflammation. Mice with a knockout of the Muc2 gene, encoding the main glycoprotein component of the mucus, demonstrate a close contact of the microbes with the gut epithelium which leads to chronic inflammation resembling IBD. Here we demonstrate that the Muc2−/− mice harboring a gut protozoan infection Tritrichomonas sp. are susceptible to an antibiotic-induced depletion of the bacterial microbiota. Suppression of the protozoan infection with efficient metronidazole dosage or L-fucose administration resulted in amelioration of an illness observed in antibiotic-treated Muc2−/− mice. Fucose is a monosaccharide presented abundantly in gut glycoproteins, including Mucin2, and is known to be involved in host–microbe interactions, in particular in microbe adhesion. We suppose that further investigation of the role of fucose in protozoan adhesion to host cells may be of great value.

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Spatial metabolomics of in situ, host-microbe interactions

10.1101/555045 ◽

2019 ◽

Cited By ~ 2

Author(s):

Benedikt K Geier ◽

Emilia Sogin ◽

Dolma Michellod ◽

Moritz Janda ◽

Mario Kompauer ◽

...

Keyword(s):

Microbial Interactions ◽

Host Cells ◽

Metabolic Phenotype ◽

Community Members ◽

Metabolic Phenotypes ◽

Culture Independent ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Atmospheric Pressure Mass Spectrometry

Spatial metabolomics describes the location and chemistry of small molecules involved in metabolic phenotypes, defense molecules and chemical interactions in natural communities. Most current techniques are unable to spatially link the genotype and metabolic phenotype of microorganisms in situ at a scale relevant to microbial interactions. Here, we present a spatial metabolomics pipeline (metaFISH) that combines fluorescence in situ hybridization (FISH) microscopy and high-resolution atmospheric pressure mass spectrometry imaging (AP-MALDI-MSI) to image host-microbe symbioses and their metabolic interactions. metaFISH aligns and integrates metabolite and fluorescent images at the micrometer-scale for a spatial assignment of host and symbiont metabolites on the same tissue section. To illustrate the advantages of metaFISH, we mapped the spatial metabolome of a deep-sea mussel and its intracellular symbiotic bacteria at the scale of individual epithelial host cells. Our analytical pipeline revealed metabolic adaptations of the epithelial cells to the intracellular symbionts, a variation in metabolic phenotypes in one symbiont type, and novel symbiosis metabolites. metaFISH provides a culture-independent approach to link metabolic phenotypes to community members in situ - a powerful tool for microbiologists across fields.

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Perspectives on Remorin Proteins, Membrane Rafts, and Their Role During Plant–Microbe Interactions

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-07-10-0166 ◽

2011 ◽

Vol 24 (1) ◽

pp. 7-12 ◽

Cited By ~ 75

Author(s):

Iris K. Jarsch ◽

Thomas Ott

Keyword(s):

Current Knowledge ◽

Root Nodules ◽

Current Data ◽

Effector Proteins ◽

Host Cells ◽

Membrane Microdomains ◽

Membrane Rafts ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Molecular Patterns

Invasion of host cells by pathogenic or mutualistic microbes requires complex molecular dialogues that often determine host survival. Although several components of the underlying signaling cascades have recently been identified and characterized, our understanding of proteins that facilitate signal transduction or assemble signaling complexes is rather sparse. Our knowledge of plant-specific remorin proteins, annotated as proteins with unknown function, has recently advanced with respect to their involvement in host–microbe interactions. Current data demonstrating that a remorin protein restricts viral movement in tomato leaves and the importance of a symbiosis-specific remorin for bacterial infection of root nodules suggest that these proteins may serve such regulatory functions. Direct interactions of other remorins with a resistance protein in Arabidopsis thaliana, and differential phosphorylation upon perception of microbial-associated molecular patterns and during expression of bacterial effector proteins, strongly underline their roles in plant defense. Furthermore, the specific subcellular localization of remorins in plasma membrane microdomains now provides the opportunity to visualize membrane rafts in living plants cells. There, remorins may oligomerize and act as scaffold proteins during early signaling events. This review summarizes current knowledge of this protein family and the potential roles of remorins in membrane rafts.

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Glycans in Virus-Host Interactions: A Structural Perspective

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.666756 ◽

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.

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Antivirulence Activity of the Human Gut Metabolome

mBio ◽

10.1128/mbio.01183-14 ◽

2014 ◽

Vol 5 (4) ◽

Cited By ~ 31

Author(s):

L. Caetano M. Antunes ◽

Julie A. K. McDonald ◽

Kathleen Schroeter ◽

Christian Carlucci ◽

Rosana B. R. Ferreira ◽

...

Keyword(s):

Small Molecules ◽

Chemical Cues ◽

Therapeutic Potential ◽

Host Cells ◽

Human Gut ◽

Complex Ecosystem ◽

Microbe Interactions ◽

Health And Disease ◽

Host Microbe Interactions

ABSTRACTThe mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor ofSalmonellavirulence, obliterating expression of theSalmonellapathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential.IMPORTANCEMicrobes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

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A nadA Mutation Confers Nicotinic Acid Auxotrophy in Pro-carcinogenic Intestinal Escherichia coli NC101

Frontiers in Microbiology ◽

10.3389/fmicb.2021.670005 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lacey R. Lopez ◽

Cassandra J. Barlogio ◽

Christopher A. Broberg ◽

Jeremy Wang ◽

Janelle C. Arthur

Keyword(s):

Escherichia Coli ◽

Nicotinic Acid ◽

De Novo ◽

Host Cells ◽

Gene Encoding ◽

E Coli ◽

Functional Studies ◽

Bowel Diseases ◽

Mechanistic Investigations

Inflammatory bowel diseases (IBDs) and inflammation-associated colorectal cancer (CRC) are linked to blooms of adherent-invasive Escherichia coli (AIEC) in the intestinal microbiota. AIEC are functionally defined by their ability to adhere/invade epithelial cells and survive/replicate within macrophages. Changes in micronutrient availability can alter AIEC physiology and interactions with host cells. Thus, culturing AIEC for mechanistic investigations often involves precise nutrient formulation. We observed that the pro-inflammatory and pro-carcinogenic AIEC strain NC101 failed to grow in minimal media (MM). We hypothesized that NC101 was unable to synthesize a vital micronutrient normally found in the host gut. Through nutrient supplementation studies, we identified that NC101 is a nicotinic acid (NA) auxotroph. NA auxotrophy was not observed in the other non-toxigenic E. coli or AIEC strains we tested. Sequencing revealed NC101 has a missense mutation in nadA, a gene encoding quinolinate synthase A that is important for de novo nicotinamide adenine dinucleotide (NAD) biosynthesis. Correcting the identified nadA point mutation restored NC101 prototrophy without impacting AIEC function, including motility and AIEC-defining survival in macrophages. Our findings, along with the generation of a prototrophic NC101 strain, will greatly enhance the ability to perform in vitro functional studies that are needed for mechanistic investigations on the role of intestinal E. coli in digestive disease.

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A microfluidic cell-trapping device for single-cell tracking of host–microbe interactions

Lab on a Chip ◽

10.1039/c6lc00649c ◽

2016 ◽

Vol 16 (17) ◽

pp. 3276-3285 ◽

Cited By ~ 17

Author(s):

Matthieu J. Delincé ◽

Jean-Baptiste Bureau ◽

Ana Teresa López-Jiménez ◽

Pierre Cosson ◽

Thierry Soldati ◽

...

Keyword(s):

Single Cell ◽

Microfluidic Device ◽

Cell Tracking ◽

Bacterial Pathogens ◽

Host Cells ◽

Cell Trapping ◽

A Cell ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Trapping Device

We present a cell-trapping microfluidic device (“InfectChip”) to study the interaction of bacterial pathogens with motile host cells.

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Interactions between the gut microbiome and host gene regulation in cystic fibrosis

10.1101/596312 ◽

2019 ◽

Author(s):

Gargi Dayama ◽

Sambhawa Priya ◽

David E. Niccum ◽

Alexander Khoruts ◽

Ran Blekhman

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cystic Fibrosis ◽

Gut Microbiome ◽

Critical Role ◽

Host Gene ◽

Healthy Controls ◽

Host Gene Expression ◽

Microbe Interactions ◽

Host Microbe Interactions

AbstractCystic Fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in theCFTRgene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have lead to markedly increased longevity of patients with CF, but new complications have emerged, such as early onset of colorectal cancer (CRC). Although the pathogenesis of CRC in CF remains unclear, altered host-microbe interactions might play a critical role. Here, we characterize the changes in the gut microbiome and host gene expression in colonic mucosa of CF patients relative to healthy controls. We find that CF patients show decreased microbial diversity, decreased abundance of taxa such asButyricimonas, Sutterella,and Ruminococcaceae, and increased abundance of other taxa, such as Actinobacteria and Firmicutes. We find that 1543 genes, includingCFTR,show differential expression in the colon of CF patients compared to healthy controls. Interestingly, we find that these genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of CRC, tumor suppression, cellular dysfunction, p53 and mTOR signaling pathways. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression, and identified CRC-related genes, includingLCN2andDUOX2,for which gene expression is correlated with the abundance of CRC-associated bacteria, such as Ruminococcaceae andVeillonella. Our results provide new insight into the role of host-microbe interactions in the etiology of CRC in CF.

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The Gut Microbiome and Inflammatory Bowel Diseases

Annual Review of Medicine ◽

10.1146/annurev-med-042320-021020 ◽

2021 ◽

Vol 73 (1) ◽

Author(s):

Yue Shan ◽

Mirae Lee ◽

Eugene B. Chang

Keyword(s):

Gut Microbiota ◽

Inflammatory Bowel Diseases ◽

Gut Microbiome ◽

Annual Review ◽

Publication Date ◽

Bowel Diseases ◽

Microbe Interactions ◽

Inflammatory Bowel ◽

Host Microbe Interactions ◽

And Function

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host–microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. In this article, we review the most recent advances in understanding the relationship between the gut microbiota and IBD and highlight the importance of going beyond establishing description and association to gain mechanistic insights into causes and consequences of IBD. The review aims to contextualize recent findings to form conceptional frameworks for understanding the etiopathogenesis of IBD and for the future development of microbiome-based diagnostics and interventions. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Exposure of the Host-Associated Microbiome to Nutrient-Rich Conditions May Lead to Dysbiosis and Disease Development—an Evolutionary Perspective

mBio ◽

10.1128/mbio.00355-19 ◽

2019 ◽

Vol 10 (3) ◽

Cited By ~ 8

Author(s):

Tim Lachnit ◽

Thomas C. G. Bosch ◽

Peter Deines

Keyword(s):

Inflammatory Diseases ◽

Developed Countries ◽

Disease Development ◽

Inflammatory Reactions ◽

Bowel Diseases ◽

Microbe Interactions ◽

Inflammatory Bowel ◽

Host Microbe Interactions ◽

Increased Activity ◽

Human Specific

ABSTRACTInflammatory diseases, such as inflammatory bowel diseases, are dramatically increasing worldwide, but an understanding of the underlying factors is lacking. We here present an ecoevolutionary perspective on the emergence of inflammatory diseases. We propose that adaptation has led to fine-tuned host-microbe interactions, which are maintained by secreted host metabolites nourishing the associated microbes. A constant elevation of nutrients in the gut environment leads to an increased activity and changed functionality of the microbiota, thus severely disturbing host-microbe interactions and leading to dysbiosis and disease development. In the past, starvation and pathogen infections, causing diarrhea, were common incidences that reset the gut bacterial community to its “human-specific-baseline.” However, these natural clearing mechanisms have been virtually eradicated in developed countries, allowing a constant uncontrolled growth of bacteria. This leads to an increase of bacterial products that stimulate the immune system and ultimately might initiate inflammatory reactions.

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The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation

Cells ◽

10.3390/cells9051234 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1234 ◽

Cited By ~ 4

Author(s):

Chiara Amoroso ◽

Federica Perillo ◽

Francesco Strati ◽

Massimo Fantini ◽

Flavio Caprioli ◽

...

Keyword(s):

Gut Microbiota ◽

Immune Responses ◽

Targeted Therapies ◽

Intestinal Inflammation ◽

Cost Effective ◽

Bowel Diseases ◽

Current Therapies ◽

Microbe Interactions ◽

Inflammatory Bowel ◽

Host Microbe Interactions

Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host−microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.

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