TY - JOUR
T1 - Unfermented β-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients
AU - Armstrong, Heather K.
AU - Bording-Jorgensen, Michael
AU - Santer, Deanna M.
AU - Zhang, Zhengxiao
AU - Valcheva, Rosica
AU - Rieger, Aja M.
AU - Sung-Ho Kim, Justin
AU - Dijk, Stephanie I.
AU - Mahmood, Ramsha
AU - Ogungbola, Olamide
AU - Jovel, Juan
AU - Moreau, France
AU - Gorman, Hayley
AU - Dickner, Robyn
AU - Jerasi, Jeremy
AU - Mander, Inderdeep K.
AU - Lafleur, Dawson
AU - Cheng, Christopher
AU - Petrova, Alexandra
AU - Jeanson, Terri Lyn
AU - Mason, Andrew
AU - Sergi, Consolato M.
AU - Levine, Arie
AU - Chadee, Kris
AU - Armstrong, David
AU - Rauscher, Sarah
AU - Bernstein, Charles N.
AU - Carroll, Matthew W.
AU - Huynh, Hien Q.
AU - Walter, Jens
AU - Madsen, Karen L.
AU - Dieleman, Levinus A.
AU - Wine, Eytan
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - 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).
AB - 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).
KW - Dietary Fibers
KW - Fermentation
KW - IBD
KW - Microbiome
UR - http://www.scopus.com/inward/record.url?scp=85142652058&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2022.09.034
DO - 10.1053/j.gastro.2022.09.034
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C2 - 36183751
AN - SCOPUS:85142652058
SN - 0016-5085
VL - 164
SP - 228
EP - 240
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -