biostudies-literatureUnknownOzkan ANIBIB NIH HHSNIDDK NIH HHSInflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma, sex hormones, and peristalsis-associated mechanical deformations play a key role in driving inflammation, fibrosis, and disease progression in male and female IBD patients.medRxiv : the preprint server for health sciences2024.12.05.24318563https://www.ebi.ac.uk/biostudies/studies/S-EPMC11643285biostudies-literatureHuman Organ Chips Reveal New Inflammatory Bowel Disease Drivers.PMC11643285T32 DK007199T32 EB016652P30 DK034854Ozkan AWinton DJCalderon KStejskalova ACarlotti EFerri LEMcDonald SACHall SMerry GEPosey RRSperry MRiccardi RHorvath VBordeianou LIngber DEChou DBGoyal GPiatok JfalseHuman Organ Chips Reveal New Inflammatory Bowel Disease Drivers.Inflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma, sex hormones, and peristalsis-associated mechanical deformations play a key role in driving inflammation, fibrosis, and disease progression in male and female IBD patients.2025-01-01T00:00:00Z2025 May2026-07-03T03:25:12.125Z2025-04-04T21:45:37.339ZS-EPMC116432853967741610.1101/2024.12.05.24318563