scholarly journals Versatile human in vitro triple coculture model coincubated with adhered gut microbes reproducibly mimics pro‐inflammatory host‐microbe interactions in the colon

2021 ◽  
Vol 35 (12) ◽  
Author(s):  
Annelore Beterams ◽  
Kim De Paepe ◽  
Laure Maes ◽  
India Jane Wise ◽  
Herlinde De Keersmaecker ◽  
...  
Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 372
Author(s):  
Feyisara Eyiwumi Oni ◽  
Qassim Esmaeel ◽  
Joseph Tobias Onyeka ◽  
Rasheed Adeleke ◽  
Cedric Jacquard ◽  
...  

Pseudomonas lipopeptides (Ps-LPs) play crucial roles in bacterial physiology, host–microbe interactions and plant disease control. Beneficial LP producers have mainly been isolated from the rhizosphere, phyllosphere and from bulk soils. Despite their wide geographic distribution and host range, emerging evidence suggests that LP-producing pseudomonads and their corresponding molecules display tight specificity and follow a phylogenetic distribution. About a decade ago, biocontrol LPs were mainly reported from the P. fluorescens group, but this has drastically advanced due to increased LP diversity research. On the one hand, the presence of a close-knit relationship between Pseudomonas taxonomy and the molecule produced may provide a startup toolbox for the delineation of unknown LPs into existing (or novel) LP groups. Furthermore, a taxonomy–molecule match may facilitate decisions regarding antimicrobial activity profiling and subsequent agricultural relevance of such LPs. In this review, we highlight and discuss the production of beneficial Ps-LPs by strains situated within unique taxonomic groups and the lineage-specificity and coevolution of this relationship. We also chronicle the antimicrobial activity demonstrated by these biomolecules in limited plant systems compared with multiple in vitro assays. Our review further stresses the need to systematically elucidate the roles of diverse Ps-LP groups in direct plant–pathogen interactions and in the enhancement of plant innate immunity.


2016 ◽  
Vol 113 (26) ◽  
pp. 7041-7046 ◽  
Author(s):  
Sujit S. Datta ◽  
Asher Preska Steinberg ◽  
Rustem F. Ismagilov

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host–microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer–mucus interactions can be described using a thermodynamic model based on Flory–Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice—whose microbiota degrade gut polymers—did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes.


Author(s):  
Won‐Suk Song ◽  
Sung Gyu Shin ◽  
Sung‐Hyun Jo ◽  
Jae‐Seung Lee ◽  
Hyo‐Jin Jeon ◽  
...  

2021 ◽  
Author(s):  
Hugo Condessa Barreto ◽  
Beatriz Abreu ◽  
Isabel Gordo

Iron is critical in host-microbe interactions, and its availability is under tight regulation in the mammalian gut. Antibiotics and inflammation are known to perturb iron availability in the gut, which could subsequently alter host-microbe interactions. Here, we show that an adaptive allele of iscR, encoding a major regulator of iron homeostasis of Escherichia coli, is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, other members of the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host's innate immune system protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of the iscR allele. Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.


2020 ◽  
Vol 6 (3) ◽  
pp. 155
Author(s):  
Maritza Torres ◽  
Hans de Cock ◽  
Adriana Marcela Celis Ramírez

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host–microbe interactions of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review, we present different models that have been implemented in fungal infections studies with greater attention to Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host–microbe interactions. This is due to the fact that these systems have been shown to have reliable results, which correlate with those obtained from mammalian models. Examples of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.


Author(s):  
Janneke Elzinga ◽  
John van der Oost ◽  
Willem M. de Vos ◽  
Hauke Smidt

SUMMARYThe human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticatedin vitrocell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied toin vivomodels that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accuratein vitromodels of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut “core microbiota” are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.


mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Charlotte De Rudder ◽  
Marta Calatayud Arroyo ◽  
Sarah Lebeer ◽  
Tom Van de Wiele

ABSTRACT The epithelium of the human sinonasal cavities is colonized by a diverse microbial community, modulating epithelial development and immune priming and playing a role in respiratory disease. Here, we present a novel in vitro approach enabling a 3-day coculture of differentiated Calu-3 respiratory epithelial cells with a donor-derived bacterial community, a commensal species (Lactobacillus sakei), or a pathobiont (Staphylococcus aureus). We also assessed how the incorporation of macrophage-like cells could have a steering effect on both epithelial cells and the microbial community. Inoculation of donor-derived microbiota in our experimental setup did not pose cytotoxic stress on the epithelial cell layers, as demonstrated by unaltered cytokine and lactate dehydrogenase release compared to a sterile control. Epithelial integrity of the differentiated Calu-3 cells was maintained as well, with no differences in transepithelial electrical resistance observed between coculture with donor-derived microbiota and a sterile control. Transition of nasal microbiota from in vivo to in vitro conditions maintained phylogenetic richness, and yet a decrease in phylogenetic and phenotypic diversity was noted. Additional inclusion and coculture of THP-1-derived macrophages did not alter phylogenetic diversity, and yet donor-independent shifts toward higher Moraxella and Mycoplasma abundance were observed, while phenotypic diversity was also increased. Our results demonstrate that coculture of differentiated airway epithelial cells with a healthy donor-derived nasal community is a viable strategy to mimic host-microbe interactions in the human upper respiratory tract. Importantly, including an immune component allowed us to study host-microbe interactions in the upper respiratory tract more in depth. IMPORTANCE Despite the relevance of the resident microbiota in sinonasal health and disease and the need for cross talk between immune and epithelial cells in the upper respiratory tract, these parameters have not been combined in a single in vitro model system. We have developed a coculture system of differentiated respiratory epithelium and natural nasal microbiota and incorporated an immune component. As indicated by absence of cytotoxicity and stable cytokine profiles and epithelial integrity, nasal microbiota from human origin appeared to be well tolerated by host cells, while microbial community composition remained representative for that of the human (sino)nasal cavity. Importantly, the introduction of macrophage-like cells enabled us to obtain a differential readout from the epithelial cells dependent on the donor microbial background to which the cells were exposed. We conclude that both model systems offer the means to investigate host-microbe interactions in the upper respiratory tract in a more representative way.


2021 ◽  
Author(s):  
Shengbo Wu ◽  
Shujuan Yang ◽  
Manman Wang ◽  
Hao Wu ◽  
Chunjiang Liu ◽  
...  

Abstract Background:Various diseases and health are closely related to different gut microbes, which own complex interactions with diverse drugs, while the detailed targets for drug-microbe interactions are still limited and investigated separately. Quorum sensing (QS), a potential target for dealing with drug resistant, are yet to be further explored systematically for drug-microbe interactions. Furthermore, many existing studies have reported diverse casual associations among drugs, gut microbes, and diseases, which call for a systematic framework and repository to reveal their intricate interactions.Results:In this study, interactions between microbes and more than 8000 drugs have been systematically studied targeting on microbial quorum sensing receptors (LuxR, LasR, TraR, CviR, PqsR, QscR, YenR, SdiA, LsrB, LuxP, CckA) combined docking-based virtual screening technique and in vitro experimental validation. We have also illustrated the potential drug-microbe interaction network based on the predicted docking-based results to to have a more comprehensive illustration for the drug-microbe interactions, along with obtaining 14 possible potential broad-spectrum drugs for all of the 11 QS receptors. Furthermore, we have constructed a systematic framework including various connections for drugs, receptors, microbes, and diseases to form a comprehensive repository and network, which can give the QS-based underlying mechanisms for the reported causal associations between drugs and microbes at the phenotypic level. The framework, repository, and network will promote the understanding on personalized medicine and developing potential therapies for diverse diseases. Conclusions: Taken together, we curated and predicted various interactions carefully for drugs, receptors, microbes, and diseases to form a comprehensive framework, repository, and network for QS-based drug-microbe-disease interactions. This work contributes to the paradigm for the construction of the more comprehensive molecule-receptor-microbe-disease interaction network for human health that may form one of the key knowledge maps of the precision medicine in the future.


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