medRxiv : the preprint server for health sciences · 2025
Mechanistic insights into microbiome-dependent and personalized responses to dietary fibre in a randomized controlled trial.
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Armet Anissa M, Li Fuyong, Deehan Edward C, Nikolaeva Daria D, Delannoy-Bruno Omar, Siegwald Léa, Berger Bernard, Castelli Kaori Minehira, Rodionov Dmitry A, Arzamasov Aleksandr A, Liu Junhong, Seethaler Benjamin, Cole Janis L, Nguyen Khoi Nguyen, Jin Mingliang, Zhao Yuan-Yuan, Sharma Arya M, Curtis Jonathan M, Proctor Spencer D, Bischoff Stephan C, Wismer Wendy V, Osterman Andrei L, Bakal Jeffrey A, Greiner Russell, Field Catherine J, Knights Dan, Prado Carla M, Walter Jens
Аннотация
UNLABELLED: Dietary fiber supplementation can reduce cardiometabolic risk, but its effective use is limited by incomplete understanding of fibre-microbiome interactions and highly individualized responses. We tested acacia gum (AG; fermentable fibre), resistant starch type 4 (RS4; fermentable fibre), and microcrystalline cellulose (MCC; non-fermentable control fibre) in a six-week randomized trial in adults with excess body weight. Multi-omics profiling revealed distinct, structure-specific microbiota and short-chain fatty acid shifts with AG and RS4, which were not directly linked to physiological outcomes. Improvements in inflammation, gut barrier function, and satiety occurred across all arms, indicating fermentation-independent effects. AG reduced plasma ghrelin, linked to microbial carbohydrate-active enzyme genes targeting its structures. Machine-learning models predicted individualized, fiber-specific effects on blood pressure (AG) and C-reactive protein (RS4) from microbial pathways and fecal bile acids. These findings delineate fermentation-dependent and independent mechanisms of fibre action and provide a mechanistic basis for personalized fibre supplementation.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02322112.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02322112.