Abstract
Fiber-based therapies focus on butyrate production, a process often dysregulated in inflammatory bowel disease (IBD), but seldomly examine other metabolites or functional pathways. Here, we systematically profiled ex vivo responses of 66 pediatric IBD microbiomes to nine resistant starches (RS), with extensive multi-omic characterization in a subset. Our study demonstrates that inter-individual variability dominates over RS-specific effects, yielding consistent yet highly personalized fermentation phenotypes, microbial compositional shifts, and metabolite outputs. Beyond butyrate, we identify previously unreported RS fermentation metabolites, revealing hidden functional pathways and cross-feeding interactions not captured by conventional short chain fatty acid-focused analyses. Metaproteomic profiling further revealed a coordinated shift from host mucin-degrading activity toward RS utilization. Together, these findings show that RS fermentation is shaped by both RS type and participant microbiome composition, and establish the RapidAIM ex vivo platform as a fiber personalization pipeline fit for interventions aimed at restoring microbial functions disrupted in human diseases.
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Acknowledgements
Instrumentation was provided in part by the University of Ottawa Material Characterization (MatChar) Core Facility. This research was enabled in part by support provided by the Digital Research Alliance of Canada (alliancecan.ca). Metabolomics data were generated at the Calgary Metabolomics Research Facility (CMRF), supported by the International Microbiome Centre and the Canada Foundation for Innovation. DRM was supported in part through a Distinguished Clinical Chair in Pediatric IBD through the Faculty of Medicine, University of Ottawa. We thank Dr. Serge Desgreniers for assistance with FTIR, Dr. Jeffrey Ovens with X-ray diffraction, Dr. Yun Liu with scanning electron microscopy, Ruth Singleton, Adrian Gowing, and Nathan Baird for sample collection logistics, and Dr. Leyuan Li, Dr. Zhibin Ning, Adrian Beltran, Alex Dewar, Mais Jubouri, Sara Qin, and Krystal Walker for technical assistance.This work was supported by the Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-149), the Ontario Ministry of Economic Development and Innovation (project number 13440) and the Weston Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding bodies.
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D.F., D.R.M., and A.S. are co-founders of Medbiome Inc. J.M. serves as a consultant for Medbiome Inc. All other authors declare no competing interests.
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Dobranowski, P., Duan, H., Butcher, J. et al. Individual variability shapes ex vivo responses to resistant starch in inflammatory bowel disease derived microbiomes. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-01003-w
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DOI: https://doi.org/10.1038/s41522-026-01003-w
