A Gut-on-a-Chip Incorporating Human Faecal Samples and Peristalsis Predicts Responses to Immune Checkpoint Inhibitors for Melanoma

Authors

Mattia Ballerini
Serena Galiè
Punit Tyagi
Carlotta Catozzi
Hariam Raji
Amir Nabinejad
Angeli D G Macandog
Alessandro Cordiale
Bianca Ionela Slivinschi
Karol K Kugiejko
Martina Freisa
Paola Occhetta
Jennifer A Wargo
Pier F Ferrucci
Emilia Cocorocchio
Nicola Segata
Andrea Vignati
Andrey Morgun
Michela Deleidi
Teresa Manzo
Marco Rasponi
Luigi Nezi

Publication Date

6-1-2025

Journal

Nature Biomedical Engineering

DOI

10.1038/s41551-024-01318-z

PMID

39939548

PMCID

PMC12176660

PubMedCentral® Posted Date

2-12-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome-host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome-host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human induced pluripotent stem cells, with the two channels separated by a collagen matrix. By incorporating faecal samples from patients with melanoma into the intestinal channel and by performing multiomic analyses, we uncovered epithelium-specific biomarkers and microbial factors that correlate with clinical outcomes in patients with melanoma and that the microbiome of non-responders has a reduced ability to buffer cellular stress and self-renew. The gut-on-a-chip model may help identify prognostic biomarkers and therapeutic targets.

Keywords

Humans, Melanoma, Immune Checkpoint Inhibitors, Lab-On-A-Chip Devices, Gastrointestinal Microbiome, Feces, Peristalsis, Organoids, Induced Pluripotent Stem Cells, Mice, Endothelial Cells, Animals

Published Open-Access

yes

Recommended Citation

Ballerini, Mattia; Galiè, Serena; Tyagi, Punit; et al., "A Gut-on-a-Chip Incorporating Human Faecal Samples and Peristalsis Predicts Responses to Immune Checkpoint Inhibitors for Melanoma" (2025). Faculty, Staff and Student Publications. 5133.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5133