An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium...

Area of Science:

• * Gastroenterology and Immunology
• * Microbiome Research
• * Microphysiological Systems

Background:

• * Understanding gut microbe-epithelial-immune cell crosstalk is vital for gut health.
• * Existing systems lack long-term co-culture capabilities for oxygen-intolerant microbes and human innate immune cells.
• * This limitation hinders controlled studies of microbe-immune interactions.

Purpose of the Study:

• * To establish a novel gut epithelium-microbe-immune (GuMI) microphysiological system.
• * To investigate the role of antigen-presenting cells (APCs) and T cells in modulating immune responses to commensal bacteria.
• * To analyze gene transcription and cytokine secretion in response to *Faecalibacterium prausnitzii*.

Main Methods:

• * Development of the GuMI system for long-term co-culture of colonic epithelium, *Faecalibacterium prausnitzii*, dendritic cells, macrophages, and CD4+ naive T cells.
• * Multiplex cytokine assays to measure secreted factors.
• * Quantitative PCR to assess gene transcription levels of inflammatory markers.

Main Results:

• * APCs significantly increased cytokine and chemokine secretion compared to systems without APCs.
• * *F. prausnitzii* upregulated pro-inflammatory genes (TLR1, IFNA1) in colonic epithelium without altering cytokine secretion.
• * T cells decreased specific gene transcription (TLR1, IFNA1, IDO1) while increasing IL8 secretion in response to *F. prausnitzii*.

Conclusions:

• * The GuMI system effectively supports long-term co-culture of diverse gut components.
• * Individual immune cell types differentially regulate immune responses to *F. prausnitzii*.
• * The GuMI platform is valuable for studying microbe-epithelial-immune interactions in health and disease.