Unfermented β-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients

Heather K. Armstrong*, Michael Bording-Jorgensen, Deanna M. Santer, Zhengxiao Zhang, Rosica Valcheva, Aja M. Rieger, Justin Sung-Ho Kim, Stephanie I. Dijk, Ramsha Mahmood, Olamide Ogungbola, Juan Jovel, France Moreau, Hayley Gorman, Robyn Dickner, Jeremy Jerasi, Inderdeep K. Mander, Dawson Lafleur, Christopher Cheng, Alexandra Petrova, Terri Lyn JeansonAndrew Mason, Consolato M. Sergi, Arie Levine, Kris Chadee, David Armstrong, Sarah Rauscher, Charles N. Bernstein, Matthew W. Carroll, Hien Q. Huynh, Jens Walter, Karen L. Madsen, Levinus A. Dieleman, Eytan Wine*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background & aims: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. Methods: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. Results: Unfermented dietary β-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining β-fructan supplementation. The proinflammatory response to intact β-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of β-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. Conclusion: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).

Original languageEnglish
Pages (from-to)228-240
Number of pages13
Issue number2
StatePublished - Feb 2023


  • Dietary Fibers
  • Fermentation
  • IBD
  • Microbiome


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