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<p>Preterm infants born &lt;32 weeks gestation have abnormal microbial colonisation and dysregulated inflammation within the gut. Preterm infant-derived intestinal organoids (PIOs) represent a valuable model for investigating gut microbiome-host interactions and inflammatory responses. We optimised an inflammation model in PIO monolayers incubated within an anaerobic co-culture system that recreates the physiological oxygen gradient of the intestinal epithelium. We trialled multiple stimuli, including live and heat-killed pathobiont consortia, lipopolysaccharide (LPS) and flagellin. We found that a combination of apical LPS and basolateral flagellin, incubated for 3 h, elicited the most robust response. This was characterised by enhanced pro-inflammatory cytokine secretion, the potential for chemokine-driven immune recruitment, TNFα and IL17C pathway signalling, shifts from NF-κB to AP-1-mediated responses, and signs of tissue remodelling. This provides a framework for appropriate study design to disentangle the impacts of microbiome-host interactions in health and disease using intestinal organoids.</p>

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Optimising the induction of inflammation within preterm infant-derived intestinal epithelial organoids

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Jonathan A. Chapman,
  • Andrew M. Frey,
  • Maria Emilia Dueñas,
  • Jeremy M. Palmer,
  • Andrea C. Masi,
  • Nicholas D. Embleton,
  • Matthias Trost,
  • Janet E. Berrington,
  • Christopher J. Stewart

摘要

Preterm infants born <32 weeks gestation have abnormal microbial colonisation and dysregulated inflammation within the gut. Preterm infant-derived intestinal organoids (PIOs) represent a valuable model for investigating gut microbiome-host interactions and inflammatory responses. We optimised an inflammation model in PIO monolayers incubated within an anaerobic co-culture system that recreates the physiological oxygen gradient of the intestinal epithelium. We trialled multiple stimuli, including live and heat-killed pathobiont consortia, lipopolysaccharide (LPS) and flagellin. We found that a combination of apical LPS and basolateral flagellin, incubated for 3 h, elicited the most robust response. This was characterised by enhanced pro-inflammatory cytokine secretion, the potential for chemokine-driven immune recruitment, TNFα and IL17C pathway signalling, shifts from NF-κB to AP-1-mediated responses, and signs of tissue remodelling. This provides a framework for appropriate study design to disentangle the impacts of microbiome-host interactions in health and disease using intestinal organoids.