Weight, habitual fibre intake, and microbiome composition predict tolerance to fructan supplementation

Abstract

Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults (n = 40) who consumed 18 g/day inulin or placebo. We found that individuals weighing more or habitually consuming higher fibre exhibited the best tolerance. Furthermore, we identified associations between gut microbiome composition and host tolerance. Specifically, higher levels of Christensenellaceae R-7 group were associated with gastrointestinal discomfort, and a machine-learning-based approach successfully predicted high levels of flatulence, with [Ruminococcus] torques group and (Oscillospiraceae) UCG-002 sp. identified as key predictive taxa. These data reveal trends that can help guide personalised recommendations for initial inulin dosage. Our results support prior ecological findings indicating that fibre supplementation has the greatest impact on individuals whose baseline fibre intake is lowest.

Keywords:

• Microbiome
• inulin
• dietary fibre
• gastroenterology
• bioinformatics

Acknowledgments

We would like to Danielle Anderson and Ken Racicot for providing the snack bars used in the study; Stephan Theis for guidance on inulin dosage and tolerance; Tonya Snipes, Lisa Alston-Latta, and Margaret Huggins for keeping our lab spaces and glassware clean; and our study volunteers for their participation.

Patent consent

PMD has received advisory/speaker fees from Clearview, Lumos, UMethod, Otsuka, Vitakey, Sermo, Compass, Lilly, Lundbeck, Nutricia, and Transposon. PMD serves on the board of Apollo and LiveLoveLaugh. PMD owns shares in Alzheon, UMethod and Transposon. PMD is a co-inventor on patents for the diagnosis or treatment of Alzheimer disease.

Author contributions

Conceptualisation: JL, DD, HKD, SJ, GSG, PMD, LAD; Data curation: JL; Formal analysis: JL, BCN; Funding acquisition: LAD; Investigation: JL, VMC, HKD, EPD, SJ; Software: JL, BCN; Visualisation: JL, BCN; Writing – original draft: JL, BCN, MK; Writing – review & editing: JL, VMC, DD, BCN, HKD, EPD, SJ, MK, GSG, PMD, LAD.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data and code used to generate the figures presented in this paper are publicly available at https://github.com/jrletourneau/Inulin_side_effects_code. Sequence data are publicly available via the European Nucleotide Archive as demultiplexed reads with the accession number PRJEB47805.

Additional information

Funding

This work was supported by National Institutes of Health grant 1R01DK116187, Office of Naval Research grant N00014-18-1-2616, Translational Research Institute through Cooperative Agreement NNX16AO69A, the Damon Runyon Cancer Research Foundation, and the Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill [NIDDK P30DK034987]. This study used a high-performance computing facility partially supported from the North Carolina Biotechnology Center by grant 2016-IDG-1013 (HARDAC+: Reproducible HPC for Next-Generation Genomics).