Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface

Eain, Marc Mac Giolla; Bagińska, Joanna; Greenhalgh, Kacy; Fritz, Joëlle V.; Zenhausern, Frédéric; Wilmes, Paul

doi:10.1016/j.eng.2017.01.011

Cited by 34 publications

(40 citation statements)

References 30 publications

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“…The alignment of these chambers provides a microbial, epithelial, and perfusion chamber. The specific outlets and inlets of each chamber allow for the inoculation of cell lines and, through the perfusion of cell growth media, can precisely control the physiochemical conditions each chamber receives [24,134,135]. This set-up builds on previous systems such that it (1) has the ability to simultaneously establish aerobic and anaerobic conditions and (2) can monitor oxygen levels in real time [134].…”

Section: Humix Modulementioning

confidence: 99%

“…Several proof-of-concept studies have highlighted the potential HuMiX to enhance our understanding of host-microbe cross-talk [134,135]. Specifically, Eain et al report that HuMiX was sufficient to co-culture Caco-2 cells and microbial cells (LGG and Bacteroides caccae) under conditions that represented the in vivo human GI tract, i.e.…”

Section: Humix Modulementioning

confidence: 99%

“…The arterial blood supply was mimicked by the addition of an oxygen-rich media in the perfusion chamber, which provided epithelial cells with oxygen from the basal surface. In doing so, the epithelium could grow in a shear-free environment, while anaerobes were present [135]. Additionally, the group were able to co-culture immune cells via the perfusion chamber and are now focusing on developing a system, Immuno-HuMiX, to study the interactions between the immune system and the intestinal microbiota in the human gut.…”

Section: Humix Modulementioning

confidence: 99%

“…Additionally, the group were able to co-culture immune cells via the perfusion chamber and are now focusing on developing a system, Immuno-HuMiX, to study the interactions between the immune system and the intestinal microbiota in the human gut. However, the authors note that despite the success in co-culture of human and microbial cells and the potential to extend this system to study diet, drug screening, discovery, and delivery, these cell types cannot fully represent the complex cellular makeup of the entire intestinal tract [134,135].…”

Section: Humix Modulementioning

confidence: 99%

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Organoids, organs-on-chips and other systems, and microbiota

May

Evans

Parry

2017

Emerging Topics in Life Sciences

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The human gut microbiome is considered an organ in its entirety and has been the subject of extensive research due to its role in physiology, metabolism, digestion, and immune regulation. Disequilibria of the normal microbiome have been associated with the development of several gastrointestinal diseases, but the exact underlying interactions are not well understood. Conventional in vivo and in vitro modelling systems fail to faithfully recapitulate the complexity of the human host-gut microbiome, emphasising the requirement for novel systems that provide a platform to study human host-gut microbiome interactions with a more holistic representation of the human in vivo microenvironment. In this review, we outline the progression and applications of new and old modelling systems with particular focus on their ability to model and to study host-microbiome cross-talk.

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Section: Humix Modulementioning

confidence: 99%

Section: Humix Modulementioning

confidence: 99%

Section: Humix Modulementioning

confidence: 99%

Section: Humix Modulementioning

confidence: 99%

See 2 more Smart Citations

Organoids, organs-on-chips and other systems, and microbiota

May

Evans

Parry

2017

Emerging Topics in Life Sciences

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“…Analysis of gut-microbiome crosstalk has almost exclusively relied on genomic or metagenomic analysis of samples collected in vivo because no method exists to establish stable complex communities of gut commensal microbes in direct contact with intestinal epithelium and their overlying mucus layer in vitro 6,7 . While animal models have been used to analyze host-microbiome interactions and their contributions to pathophysiology [8][9][10] there are no in vitro systems available to verify these interactions in human cells when cultured in direct contact with complex human microbiome.…”

mentioning

confidence: 99%

Complex human gut microbiome cultured in anaerobic human intestine chips

Baharvand

et al. 2018

Preprint

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The diverse bacterial populations that comprise the commensal microbiota of the human intestine play a central role in health and disease, yet no method is available to sustain these complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro. Here we describe a human Organ-on-a-Chip (Organ Chip) microfluidic platform that permits control and real-time assessment of physiologically-relevant oxygen gradients, and which enables co-culture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota. When compared to aerobic co-culture conditions, establishment of a transluminal hypoxia gradient sustained higher microbial diversity with over 200 unique operational taxonomic units (OTUs) from 11 different genera, and an abundance of obligate anaerobic bacteria with ratios of Firmicutes and Bacteroidetes similar to those observed in human feces, in addition to increasing intestinal barrier function. The ability to culture human intestinal epithelium overlaid by complex human gut microbial communities within microfluidic Intestine Chips may enable investigations of host-microbiome interactions that were not possible previously, and serve as a discovery tool for development of new microbiome-related therapeutics, probiotics, and nutraceuticals. ____________________________________________________________________________ One of the major recent paradigm shifts in medicine relates to the recognition of the central role that the microbiome, composed of host-specific communities of commensal microbes, plays in human health and disease 1 . While human microbiota colonize mucosal surfaces of various tissues, the gastrointestinal tract supports the

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A perfusion host‐microbe bioreactor (HMB) system that captures dynamic interactions of secreted metabolites between epithelial cells cocultured with a human gut anaerobe

Yang,

Cassaday,

Wyche

et al. 2024

Biotech & Bioengineering

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The human microbiota impacts a variety of diseases and responses to therapeutics. Due to a lack of robust in vitro models, detailed mechanistic explanations of host‐microbiota interactions cannot often be recapitulated. We describe the design and development of a novel, versatile and modular in vitro system that enables indirect coculture of human epithelial cells with anaerobic bacteria for the characterization of host‐microbe secreted metabolite interactions. This system was designed to compartmentalize anaerobes and human cells in separate chambers conducive to each organism's requisite cell growth conditions. Using perfusion, fluidic mixing, and automated sample collection, the cells continuously received fresh media, while in contact with their corresponding compartments conditioned supernatant. Supernatants from each chamber were collected in a cell‐free time‐resolved fashion. The system sustained low oxygen conditions in the anaerobic chamber, while also supporting the growth of a representative anaerobe (Bacteroides thetaiotaomicron) and a human colonic epithelial cell line (Caco‐2) in the aerobic chamber. Caco‐2 global gene expression changes in response to coculture with B. thetaiotaomicron was characterized using RNA sequencing. Extensive, targeted metabolomics analysis of over 150 central carbon metabolites was performed on the serially collected supernatants. We observed broad metabolite changes in host‐microbe coculture, compared to respective mono‐culture controls. These effects were dependent both on sampling time and the compartment probed (apical vs. basolateral). Coculturing resulted in the depletion of several important metabolites, including guanine, uridine 5'‐monophosphate, asparagine, and thiamine. Additionally, while Caco‐2 cells cultured alone predominantly affected the basolateral metabolite milieu, increased abundance of 2,3‐dihydroxyisovalerate and thymine on the basolateral side, occurred when the cells were cocultured with B. thetaiotaomicron. Thus, our system can capture the dynamic, competitive and cooperative processes between host cells and gut microbes.

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Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface

Cited by 34 publications

References 30 publications

Organoids, organs-on-chips and other systems, and microbiota

Organoids, organs-on-chips and other systems, and microbiota

Complex human gut microbiome cultured in anaerobic human intestine chips

A perfusion host‐microbe bioreactor (HMB) system that captures dynamic interactions of secreted metabolites between epithelial cells cocultured with a human gut anaerobe

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