The intestinal barrier is a dynamic ecosystem where host cells and microbial communities co-exist and communicate continuously. Understanding this interaction is crucial to decoding the functional mechanisms of live biotherapeutic products (LBPs), especially probiotics. Conventional in vitro systems fail to mimic the complexity of the gut environment, and animal models often fall short in capturing human-specific responses.
Creative Biolabs addresses this gap by offering a cutting-edge host-microbiome co-culture service on a microengineered gut barrier chip. This physiologically relevant model recapitulates the structure and function of the intestinal epithelium and allows for real-time analysis of microbial modulation on host biology, providing invaluable insight for probiotic screening, safety evaluation, and mechanism of action (MOA) discovery.
Fig. 1 The schematic representation of the human gut in a GOC model.1
Importance of Gut-on-a-Chip Co-Culture
Recreating Complexity with Precision
The gut barrier chip platform enables the simultaneous culture of intestinal epithelial cells and living microbial consortia under dynamic conditions that emulate peristalsis, flow, and oxygen gradients. This allows researchers to study microbiome-host crosstalk in a structurally and functionally relevant manner.
Addressing the Growing Demand for Probiotic Mechanistic Insight
The rise in live biotherapeutic research and regulatory interest in defining the functional mechanisms of probiotics has spurred a strong demand for more physiologically accurate models. Traditional Transwell assays lack spatial resolution and metabolic accuracy. In contrast, the chip-based co-culture system offers a high-fidelity, human-relevant platform for real-time interaction studies, high-content readouts, and functional biomarker assessment.
By incorporating advanced microfluidic engineering and primary or iPSC-derived human gut cells, this system enables mechanistic dissection of microbial activities, immune interactions, metabolite translocation, and barrier integrity under tunable conditions.
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Tailored Capabilities at Creative Biolabs
Creative Biolabs has built a robust and modular gut-on-a-chip platform to support comprehensive host-microbiome co-culture studies tailored to probiotic research. Our service is designed to enable flexibility, reproducibility, and biological accuracy at each step of the study.
1. Customizable Gut Barrier Construction
We provide chip models lined with human intestinal epithelial cells, including Caco-2, HT29-MTX, primary cells, or iPSC-derived enterocytes and goblet cells. These can be combined with mucus-producing layers and immune cell types (e.g., dendritic cells, macrophages) as required.
2. Dynamic Microfluidic Flow Control
Our system incorporates laminar flow and peristaltic-like motions to simulate intestinal fluid dynamics, ensuring more accurate cellular polarization, nutrient absorption, and mucus layer maintenance.
3. Oxygen Gradient Engineering
We can generate oxygen gradients across the chip, enabling the co-culture of anaerobic or facultative anaerobic bacteria along the apical side, mimicking in vivo gut microbiota conditions without compromising host cell viability.
4. Controlled Microbial Inoculation
Mono- or multi-species inoculation strategies are supported. Creative Biolabs provides extensive experience in handling next-generation probiotic strains such as Anaerobutyricum soehngenii, Akkermansia muciniphila, and Christensenella minuta under strict anaerobic conditions.
5. Integrated Biomarker and Imaging Readouts
Our platform supports endpoint and real-time measurements such as:
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TEER (transepithelial electrical resistance)
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Immunofluorescence for tight junction proteins
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Barrier permeability assays (e.g., FITC-dextran)
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Cytokine and metabolite quantification (e.g., ELISA, LC-MS)
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RNA-Seq, metagenomics, and transcriptomics integration
Host-Microbiome Co-Culture Service Workflow
Our service follows a streamlined, modular workflow, allowing flexibility based on research needs:
Detailed Deliverables for Each Project
Upon project completion, clients receive:
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Experimental setup documentation
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Chip imaging and integrity verification
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Barrier function data (TEER, permeability assays)
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Inflammatory and immunological marker profiles
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Quantification of microbial metabolites (e.g., SCFAs, bile acids)
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Omics-based analysis (optional)
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Comprehensive technical report with interpretation
All deliverables are tailored to specific research questions and formatted for downstream publication or regulatory documentation.
Applications Across Probiotic and Microbiome Research
Mechanistic Elucidation of Probiotic Activity
The gut chip co-culture platform allows for the mechanistic interrogation of how specific probiotic strains impact epithelial function, cytokine expression, and metabolite production in real-time.
Live Biotherapeutic Safety and Tolerability Testing
Researchers can assess probiotic effects on gut permeability, cytotoxicity, and pro-inflammatory responses under human-relevant conditions before advancing to animal models or clinical stages.
Disease Modeling for Functional Screening
Chronic inflammation, dysbiosis, and leaky gut conditions can be modeled on-chip to investigate how microbial consortia influence barrier repair and immune responses under pathophysiological conditions.
Metabolite Translocation and Host Response Profiling
The chip model enables the controlled tracking of microbially derived molecules (e.g., butyrate, indole derivatives) across the epithelial layer and downstream immune activation analysis.
Drug-Microbiota Interaction Assessment
The system can be adapted to study how small molecules, dietary components, or prebiotics affect host-microbiome dynamics, supporting functional food and drug formulation development.
Explore Related Services from Creative Biolabs
Creative Biolabs provides a comprehensive suite of complementary solutions to extend insights gained from chip-based co-cultures:
The host-microbiome co-culture service on gut barrier chips offered by Creative Biolabs represents a next-generation platform for accurate, reproducible, and mechanistic evaluation of probiotic functionality and safety. Our commitment to scientific rigor and flexible service design enables researchers to generate high-impact data that drives confident decisions in probiotic and microbiome product development.
Interested in exploring how your strains interact with the human gut epithelium? Get in touch today to discuss your project with our microbiome experts or request a customized quote.
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FAQs
What are the advantages of using a gut barrier chip for host-microbiome co-culture studies?
The gut barrier chip offers dynamic flow, oxygen gradients, and 3D architecture, enabling real-time, human-relevant analysis of microbiota-host interactions that conventional static or Transwell systems cannot replicate.
Can I co-culture anaerobic bacteria with intestinal cells using this chip system?
Yes, Creative Biolabs' platform supports oxygen gradient engineering, allowing strict or facultative anaerobes to be cultured apically while maintaining oxygenated conditions basolaterally for host epithelial and immune cells.
How does this model support mechanistic analysis of probiotic function?
Our system enables dynamic, spatially resolved assessment of how probiotic strains influence epithelial integrity, inflammatory signaling, and metabolite secretion under physiologically relevant conditions, supporting functional mechanism discovery.
Other Resources
References
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Thomas, Dimple Palanilkunnathil, et al. "Microfluidic gut-on-a-chip: fundamentals and challenges." Biosensors 13.1 (2023): 136. https://doi.org/10.3390/bios13010136
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Shin, Woojung, and Hyun Jung Kim. "3D in vitro morphogenesis of human intestinal epithelium in a gut-on-a-chip or a hybrid chip with a cell culture insert." Nature protocols 17.3 (2022): 910-939. https://doi.org/10.1038/s41596-021-00674-3
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Jalili-Firoozinezhad, Sasan, et al. "A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip." Nature biomedical engineering 3.7 (2019): 520-531. https://doi.org/10.1038/s41551-019-0397-0
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Lee, Ki Won, et al. "Gut-on-a-Chip for the Analysis of Bacteria–Bacteria Interactions in Gut Microbial Community: What Would Be Needed for Bacterial Co-Culture Study to Explore the Diet–Microbiota Relationship?." Nutrients 15.5 (2023): 1131. https://doi.org/10.3390/nu15051131
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Distributed Under Open Access license CC BY 4.0, without modification.
