Unfermented β-fructan fibers fuel inflammation in select inflammatory bowel disease patients
未发酵的β-果聚糖纤维加剧特定IBD患者的炎症反应
10.1053/j.gastro.2022.09.034
09-29, Article
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Background and aims: Inflammatory bowel diseases (IBD) are impacted by dietary factors, including non-digestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial but not all fibers are alike and some IBD patients report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in IBD patients, 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 (5g/L), or fermentation supernatants (24hr anaerobic fermentation) and immune responses (cytokine secretion [ELISA/MSD] and expression [qPCR]) 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 pro-inflammatory 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 pro-inflammatory 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 pro-inflammatory response, but only when microbes were collected from non-IBD or inactive IBD patients. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance.
Conclusion: While 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.
First Authors:
Heather K Armstrong
Correspondence Authors:
Heather K Armstrong,Eytan Wine
All Authors:
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 Jeanson,Andrew 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
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