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Soluble Corn Fiber Consumption Effects Executive Functions and Gut Microbiota in Middle to Older Age Adults: A Randomized Controlled Crossover Trial

Alvarado, D. A.; Holthaus, T. A.; Martell, S.; Southey, N. L.; Atallah, M.; Sarma, R.; Revilla, D.; Brown, M.; Mehta, T.; Khan, N. A.; Holscher, H. D.

2025-06-13 nutrition
10.1101/2025.06.12.25329532 medRxiv
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BackgroundDietary fiber may support cognition through gastrointestinal-microbiota mechanisms, but clinical evidence is limited. ObjectivesWe aimed to determine whether soluble corn fiber (SCF) improved cognition and altered fecal microbiota and fermentation end products in adults. MethodsIn a randomized, double-blind, crossover trial, 42 healthy adults (45-75y) consumed SCF (18g/d) or a maltodextrin placebo control (CON: 22g/d) for 4 weeks, separated by a washout. Cognitive outcomes included executive function with event-related potentials, relational memory, neuropsychological performance, and mood. Secondary outcomes included fecal microbiota, metabolomics, and gastrointestinal tolerance. Tertiary analyses related microbial and metabolite changes to cognitive improvements using correlation, mediation, and moderation models, and explored SCF fermentation pathways with 16S-predicted functional profiling, shotgun metagenomics and in vitro culturing. ResultsSCF improved reaction times (RT) during congruent ({beta} = -9.8 ms, 95% CI: [-18.4, -1.2], FDR P = 0.01) and incongruent ({beta} = -14.2 ms, 95% CI: [-22.8, -5.6], FDR P = 0.003) flanker trials and increased Parabacteroides ([~]4-fold, {beta} = 1.44 log, 95% CI [1.01, 1.88], FDR P < 0.001). At the SCF endpoint, congruent RT tended to be inversely associated with fecal acetate ({rho} = -0.33) and propionate ({rho} = -0.36), while Parabacteroides was marginally positively associated with acetate ({rho} = 0.34) (all FDR P < 0.1). Moderation analyses indicated that SCF-RT relation varied by Parabacteroides magnitude change. At endpoint, SCF increased predicted functional potential of carbohydrate-related KOs and pathways (FDR P < 0.05). In vitro culturing confirmed P. distasonis ferments SCF. ConclusionSCF consumption improved attentional inhibition, altered the gut microbiota, and selectively enriched Parabacteroides. Although mediation analyses did not support a direct microbiota-to-cognition pathway, moderation analyses suggested that SCF-related cognitive effects may depend in part on Parabacteroides abundance. Collectively, these findings suggest that certain cognitive benefits of SCF consumption may be partly underpinned by the gut microbiota.

Published in The Journal of Nutrition (predicted rank #14) · training set

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