Assessing the proinflammatory potential of sterile fecal microbiome filtrate from ulcerative colitis patients using an intestine-on-chip platform and automated image analysis.

Authors

Tobias Schaal, Parastoo Akbarimoghaddam, Valentin D Wegner, Arndt Steube, Elena Gardey, Adrian Feile, Mohamed I Abdelwahab Hassan, Zoltán Cseresnyés, Andreas Stallmach, Alexander S Mosig, Marc Thilo Figge, Johannes Stallhofer

Published in

Gut microbes. Volume 18. Issue 1. Pages 2701400. Dec 31, 2026. Epub Jul 28, 2026.

Abstract

Ulcerative colitis (UC) is characterized by disruptions of the gut microbiome and an exaggerated mucosal immune response in genetically susceptible individuals. Alterations in the composition of the intestinal metabolome associated with dysbiosis can trigger chronic inflammation. However, it remains unclear whether microbial dysbiosis is the cause or consequence of chronic mucosal inflammation. To address this gap, we aimed to investigate the potential pro-inflammatory effects of sterile fecal microbiome filtrate (FMF) using a microphysiological, immunocompetent intestine-on-chip (IoC) model.
Sterile FMF from UC patients with active disease (n = 6) or in remission (n = 4) and non-UC individuals (n = 5) were applied to IoC models. Cytokine responses of the epithelial and endothelial compartments were assessed after 24  h, 48  h, and 72  h of incubation, while barrier permeability was evaluated after a period of 72 h. An artificial intelligence-driven image analysis pipeline was developed to quantify structural alterations of the epithelial tissue, including damage and thickness, as well as endothelial and immune cell densities in the IoC model in response to FMF exposure.
FMF from active UC patients significantly increased proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-23, and MCP-1) in the vascular IoC compartment in a time-dependent manner. In contrast, FMF from non-UC or UC patients in remission had no significant impact on the proinflammatory cytokine response compared to untreated media control. Luminal-vascular permeability was increased following the FMF treatment regardless of its origin. Image-based analysis revealed increased epithelial tissue damage and reduced tissue thickness following FMF exposure, alongside decreased endothelial cell density and altered macrophage morphology, independent of UC disease activity.
FMF from UC patients with active disease induces a robust proinflammatory cytokine response in the IoC model, suggesting that UC-associated FMF-derived factors may contribute to the initiation of inflammatory processes relevant to UC pathogenesis. These findings are derived from a simplified intestinal barrier model and require further mechanistic and physiological validation. While image analysis revealed no significant microarchitectural differences among the three FMF groups, the pipelines established standardized metrics to evaluate the impact of FMF-derived factors on intestinal tissue integrity and immune responses, providing a framework for future IoC-based research in UC.

PMID:
42520137
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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