02864nas a2200349   4500000000100000000000100001008004100002260001500043653002100058653001700079100001300096700001800109700001900127700002100146700001900167700002100186700001900207700002700226700002000253700002300273700002200296700002200318700002200340700002000362700001800382245014200400856005500542300001000597490000700607520188600614022001402500       2026                            d  c2026-04-0110aGastroenterology10aMicrobiology1 aEva Chan1 aWing Hei Chan1 aGenevieve Kerr1 aStuart K. Archer1 aThierry Jardé1 aRebekah M. Engel1 aJodee A. Gould1 aShanika L. Amarasinghe1 aEmily L. Rutten1 aGemma L. D’Adamo1 aEmily L. Gulliver1 aLinden J. Gearing1 aSamuel C. Forster1 aEdward M. Giles1 aHelen E. Abud00aPatient-derived intestinal organoids as a model for site-specific mucosal bacterial interactions in paediatric inflammatory bowel disease  uhttps://www.nature.com/articles/s41598-026-46184-8  a153590 v163 aInflammatory bowel disease (IBD) is secondary to an abnormal immune response to the microbiota. To study this, models of host-microbe interactions that represent mucosal bacterial communities and inter-patient diversity are required. Human intestinal organoids (HIOs) are an established model to investigate epithelial responses. Here, we describe a technique of culturing bacteria directly from the sites of inflammation in IBD, while simultaneously sampling host tissue. We generated HIOs from a cohort of newly diagnosed paediatric IBD patients, without confounding treatments or comorbidities, and explored their response to site-specific bacteria. A unique biobank of matched HIOs and cultured mucosa-attached bacteria was established from 27 paediatric patients. Transcriptional profiling revealed differential gene expression between control and IBD-derived organoids. We used microinjection to introduce bacteria to the apical surface of the epithelium, to determine the effect of bacteria on host epithelial cells. We measured survival and growth of bacteria within the HIOs and tested several related bacterial isolates for their impact on the epithelium. An isolate from a control patient stimulated inflammatory signalling pathways but this was not observed in response to a closely related isolate originating from an IBD patient. This study demonstrates the feasibility of isolating bacteria and generating organoids from the same biopsy tissue, to explore personalised host-microbe interactions. The microinjections, while labour-intensive, demonstrate that closely related bacteria can induce very different epithelial responses, with downstream implications for immune response. This highlights the importance of understanding host-microbe interactions in a strain- and site-specific manner and developing techniques for personalised microbiome-based therapeutics.  a2045-2322