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Personalized Gut-Liver Microphysiological System Maps Donor-Specific Tissue-Resident Immunity and Reveals a Conserved
Biorxiv : the Preprint Server for Biology
|July 16, 2025
Summary
This study developed a personalized gut-liver model to study immune cell differences. The model revealed a shared metabolic pathway that influences immune responses across individuals.
Area of Science:
- Immunology
- Gastroenterology
- Metabolic Engineering
Background:
- Tissue-resident immune (TRI) niches are highly variable between individuals.
- Understanding these unique immune profiles is crucial for personalized medicine.
Purpose of the Study:
- To create a personalized gut-liver microphysiological system (MPS) that models individual TRI profiles.
- To investigate organ- and donor-specific immune responses and gut-liver crosstalk.
Main Methods:
- Utilized primary colon epithelium, hepatocytes, and autologous CD45⁺ TRI cells from two donors.
- Employed single-cell RNA-sequencing to analyze immune cell profiles.
- Challenged the gut compartments with microbial agonists to assess liver responses.
Main Results:
- Identified distinct TRI profiles and predicted responses between donors.
- Observed donor-specific immune programs, including Th1/Th17 polarization and B cell differentiation.
- Discovered a conserved retinoid-bile acid metabolic axis in gut-liver crosstalk that modulated inflammation.
- Demonstrated differential liver responses to microbial agonists based on donor-specific immune activation.
Conclusions:
- The personalized gut-liver MPS effectively models human immune diversity and organ-specific responses.
- A conserved metabolic dialogue coexists with and is influenced by TRI profiles.
- This model serves as a blueprint for studying immunometabolic diseases and developing precision therapeutics.
