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Ecological memory of prior nutrient exposure in the human gut microbiome


Many ecosystems have been shown to retain a memory of past conditions, which in turn affects how they respond to future stimuli. In microbial ecosystems, community disturbance has been associated with lasting impacts on microbiome structure. However, whether microbial communities alter their response to repeated stimulus remains incompletely understood. Using the human gut microbiome as a model, we show that bacterial communities retain an “ecological memory” of past carbohydrate exposures. Memory of the prebiotic inulin was encoded within a day of supplementation among a cohort of human study participants. Using in vitro gut microbial models, we demonstrated that the strength of ecological memory scales with nutrient dose and persists for days. We found evidence that memory is seeded by transcriptional changes among primary degraders of inulin within hours of nutrient exposure, and that subsequent changes in the activity and abundance of these taxa are sufficient to enhance overall community nutrient metabolism. We also observed that ecological memory of one carbohydrate species impacts microbiome response to other carbohydrates, and that an individual’s habitual exposure to dietary fiber was associated with their gut microbiome’s efficiency at digesting inulin. Together, these findings suggest that the human gut microbiome’s metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. The dynamics of this ecological memory also highlight the potential for intra-individual microbiome variation to affect the design and interpretation of interventions involving the gut microbiome.

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Fig. 1: Ecological memory of prior nutrient exposure is encoded within 24 h.
Fig. 2: Compositional, transcriptomic, and metabolic changes reflect nutritional memory in artificial guts.
Fig. 3: Bacteroides PUL activation precedes broader transcriptional and compositional changes in artificial guts.
Fig. 4: Ecological memory is cross-reactive.

Data availability

Data and code used to generate the figures presented in this paper are publicly available at Sequence data are publicly available via the European Nucleotide Archive as demultiplexed reads with the accession numbers PRJEB45244 (metatranscriptomics), PRJEB45247 (artificial gut 16S rRNA gene amplicon sequence data), and PRJEB48837 (cross-reactivity experiment 16S rRNA gene amplicon sequence data), and PRJEB47805 (human cohort 16S rRNA gene amplicon sequence data). Our lab’s 16S rRNA gene amplicon sequence data processing pipeline is also available at


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We would like to thank Justin Silverman for assistance with sequencing and model design; Andrew Grover for help sampling from the artificial guts; Danielle Anderson and Ken Racicot for providing the snack bars used in the study; Neil Surana for helpful guidance related to our literature review; Michelle Kirtley for comments on manuscript revision; Tonya Snipes, Lisa Alston-Latta, and Margaret Huggins for keeping our lab spaces and glassware clean; and our study volunteers for their participation. 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 UNC CGIBD (NIDDK P30DK034987). This study used a high-performance computing facility partially supported by grant 2016-IDG-1013 (HARDAC+: Reproducible HPC for Next-Generation Genomics) from the North Carolina Biotechnology Center. JRB received salary support from NIH 5P30DK124723, 5R01DK117491, 1U24DK129557, and 2P30AG027816.

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Conceptualization: JL, ZCH, JRB, LAD; Data curation: JL, MJM; Formal analysis: JL; Funding acquisition: LAD; Investigation: JL, ZCH, EPD, HKD, SJ, SKG, ACM, MJM, VMC; Software: JL; Visualization: JL; Writing – original draft: JL; Writing – review & editing: JL, LAD.

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Correspondence to Lawrence A. David.

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LAD previously served on the Strategic Advisory Board and held equity in the company Kaleido Biosciences.

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Letourneau, J., Holmes, Z.C., Dallow, E.P. et al. Ecological memory of prior nutrient exposure in the human gut microbiome. ISME J (2022).

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