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Interorgan Communication Between Lung and Colorectal Epithelial Cells Studied Using a Novel Multi-Organ-On-Chip

Brady Rae1,2, Verena Bood1,2, Hye-Jin Dijk1,2

  • 1Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Comprehensive Physiology
|September 15, 2025
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Summary

A new multi-organ-on-chip model reveals how lung cells damaged by pollutants communicate with gut cells. This lung-gut axis communication involves inflammatory signals, offering insights into Chronic Obstructive Pulmonary Disease (COPD) comorbidities.

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Respiratory Medicine

Background:

  • Chronic Obstructive Pulmonary Disease (COPD) is linked to systemic inflammation and a bi-directional lung-gut axis.
  • Mechanisms of interorgan communication in COPD are poorly understood due to limited in vitro models.

Purpose of the Study:

  • To develop a novel in vitro model for studying lung-gut interorgan communication.
  • To investigate the role of mediators in COPD-related lung-gut axis communication.

Main Methods:

  • A unidirectional millifluidic multi-organ-on-chip (MOoC) device was created, connecting stimulated lung epithelial cells (A549) to colorectal cells (DLD-1).
  • A549 cells were exposed to cigarette smoke extract and nylon microplastic fibers.
  • Interorgan communication was analyzed by measuring responses in DLD-1 cells to factors released by stimulated A549 cells.

Main Results:

  • Stimulated A549 cells released Damage Associated Molecular Patterns (DAMPs), including galectin-3.
  • Naïve DLD-1 cells exhibited pro-inflammatory responses, including increased IL-6 mRNA expression.
  • Barrier integrity in DLD-1 cells was compromised, evidenced by decreased CDH1 mRNA and altered E-cadherin and ZO-1 protein localization.

Conclusions:

  • The novel MOoC platform enables the study of inter-organ communication between different cell types.
  • The findings provide insights into mediators driving lung-gut axis communication in COPD.
  • This model can advance research into COPD comorbidities and systemic inflammation.