Gut-Liver Chip Model for Microbial Metabolite Evaluation

Microbial metabolites produced by the gut microbiota profoundly influence host health through complex interactions with multiple organs, particularly the liver. These metabolites—ranging from short-chain fatty acids (SCFAs) and bile acids to tryptophan derivatives and endotoxins—enter systemic circulation via the portal vein and are extensively processed by the liver. As a result, accurately modeling the gut-liver axis is essential for evaluating the functional roles and systemic impacts of microbial metabolites in preclinical research.

To address the limitations of conventional in vitro and in vivo approaches, Creative Biolabs offers an advanced gut-liver chip model that replicates the physiological architecture and dynamic interplay between intestinal and hepatic tissues. This platform enables high-resolution evaluation of microbial metabolites, mimicking absorption, first-pass metabolism, and host responses in a microfluidic, organ-on-a-chip setting. By integrating engineering precision and biological complexity, this model offers a powerful tool to dissect host–microbe interactions and their metabolic consequences.

Fig. 1 Gut-Liver Chip Schematic for Microbial Metabolite Transport. (Creative Biolabs Original)

Importance of Gut-Liver Chip Technology in Microbial Metabolite Research

Bridging a Critical Gap in Microbiome-Host Interaction Studies

The gut-liver axis serves as a central conduit for nutrient and xenobiotic metabolism, and is a key player in regulating inflammation, immunity, and metabolic homeostasis. However, traditional in vitro monoculture systems and animal models often fail to capture species-specific dynamics, fluidic shear stress, or compartmentalized responses. The gut-liver chip overcomes these hurdles by simulating:

  • Intestinal barrier function and microbial interface
  • Bidirectional communication via microfluidic circulation
  • Liver-specific metabolic transformations and clearance pathways

This makes the system exceptionally well-suited for evaluating the biotransformation, toxicity, immunogenicity, and systemic signaling potential of microbial metabolites in a controlled, physiologically relevant environment.

A Growing Demand in Preclinical Microbiome R&D

With expanding interest in next-generation probiotics (NGPs), postbiotics, and engineered microbial strains, there is a growing need to assess how microbially derived compounds affect host physiology beyond the gut. This is particularly relevant for:

  • Live biotherapeutic product (LBP) developers
  • Functional food and nutrition companies
  • Biotech and CROs exploring host-microbiome crosstalk

Creative Biolabs' gut-liver chip model provides a scalable, reproducible, and ethically favorable alternative to animal testing—accelerating R&D pipelines while generating human-relevant data.

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Integrated Capabilities of Our Gut-Liver Chip Evaluation Platform

At Creative Biolabs, we have built a high-performance microfluidic system to faithfully reconstruct the gut-liver microenvironment with specialized biological features and instrumentation.

1. Dual-Chamber Organ Chip Configuration

The platform includes two independently controlled compartments:

  • Intestinal Chamber: Cultured with human epithelial monolayers (e.g., Caco-2, iPSC-derived enterocytes) and co-cultured with immune or microbial cells as needed.
  • Liver Chamber: Seeded with primary hepatocytes or iPSC-derived hepatic spheroids to mimic liver-specific functions like drug metabolism, phase I/II enzyme activity, and bile secretion.

A dynamic flow system connects these compartments, recapitulating first-pass metabolism and bidirectional transport.

2. Compatibility with Diverse Cell Sources

We support the use of:

  • Primary human intestinal and liver cells
  • iPSC-derived epithelial and hepatocyte-like cells
  • Immune cell co-cultures (macrophages, dendritic cells)
  • Patient-derived organoids for personalized studies

Cell identity and viability are maintained through optimized extracellular matrix (ECM) compositions, flow control, and barrier integrity monitoring (e.g., TEER measurements).

3. Advanced Analytical Readouts

We provide multi-parametric endpoints including:

  • Metabolomic profiling (LC-MS/MS, GC-MS)
  • Transcriptomic responses (RNA-seq, qPCR)
  • Barrier function (permeability assays, TEER)
  • Hepatotoxicity markers (ALT, AST, albumin, urea)
  • Immunomodulation (cytokine/chemokine secretion, immune cell activation)

These comprehensive assays enable precise characterization of microbial metabolites' effects on epithelial, hepatic, and immune compartments.

Service Workflow: From Cell Seeding to Data Delivery

Our service follows a streamlined, modular workflow, allowing flexibility based on research needs:

Fig. 2 Gut-Liver Chip Model for Microbial Metabolite Evaluation Workflow. (Creative Biolabs Original)

What You'll Receive from Creative Biolabs

Clients who collaborate with Creative Biolabs receive:

  • Fully configured gut-liver chip system tailored to experimental design
  • Validated protocols for cell co-culture, metabolite dosing, and flow conditions
  • Comprehensive data package including raw and processed results, assay readouts, and interpretation
  • Digital imaging and documentation of cell morphology and viability
  • Optional bioinformatics analysis for transcriptomic and metabolomic data

All experiments are conducted under GLP-compliant conditions using sterile, quality-controlled consumables.

Applications for Gut-Liver Chip Evaluation

Preclinical Evaluation of Next-Generation Probiotics

Screen how engineered or novel microbial strains affect host barrier function, inflammatory markers, or liver metabolism—critical for mechanism of action (MOA) studies.

Metabolite Transport and Toxicity Studies

Investigate the absorption, distribution, metabolism, and excretion (ADME) profile of microbial metabolites, including their biotransformation by hepatic enzymes.

Host-Microbe Immunomodulation Analysis

Track cytokine secretion, immune cell recruitment, or endotoxin-induced inflammation following microbial metabolite exposure.

Food and Nutritional Microbiome Research

Assess how dietary components influence gut-liver signaling via microbial metabolite modulation in functional food and nutrition studies.

Personalized Disease Modeling

Use patient-derived iPSCs or organoids to evaluate microbiome-derived effects in liver diseases, metabolic syndromes, or inflammatory bowel conditions.

Related Microbiome Functional Assessment Services

Creative Biolabs offers a suite of complementary services that pair seamlessly with gut-liver chip analysis:

Creative Biolabs is a trusted CRO partner with deep expertise in organ-on-a-chip systems, microbiome-host interaction modeling, and multi-omics analytics. Our gut-liver chip model empowers researchers to move beyond static cultures and animal models, enabling more precise and predictive insights into microbial metabolite function.

To discuss your project requirements or obtain a tailored quote, contact our team of scientific experts today.

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FAQs

How does the gut-liver chip simulate first-pass metabolism of microbial metabolites?

The gut-liver chip connects intestinal and hepatic chambers through microfluidics, enabling metabolites to pass from gut to liver under flow, mimicking first-pass metabolism and hepatic transformation in a physiologically relevant, dynamic environment.

Can live microbes or complex microbial consortia be introduced into the gut compartment?

Yes. The system supports live anaerobic or facultative microbes under controlled conditions, allowing studies on microbial colonization, metabolite production, and host-microbe interactions at the epithelial interface.

Is it possible to assess the immunomodulatory effects of microbial metabolites?

Absolutely. The chip enables immune cell co-culture and quantification of cytokines, chemokines, and inflammatory markers, providing insights into how microbial metabolites influence immune signaling across the gut-liver axis.

Other Resources

References

  1. Lee, Seung Yeon, and Jong Hwan Sung. "Gut–liver on a chip toward an in vitro model of hepatic steatosis." Biotechnology and Bioengineering 115.11 (2018): 2817-2827. https://doi.org/10.1002/bit.26793
  2. Yang, Jiandong, et al. "Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease." Communications Biology 6.1 (2023): 310. https://doi.org/10.1038/s42003-023-04710-8
  3. Lucchetti, Mara, et al. "Emulating the gut–liver axis: Dissecting the microbiome's effect on drug metabolism using multiorgan-on-chip models." Current Opinion in Endocrine and Metabolic Research 18 (2021): 94-101. https://doi.org/10.1016/j.coemr.2021.03.003
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For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

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