Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults

Crystal F Haskell-Ramsay, Fiona L Dodd, Darren Smith, Lewis Cuthbertson, Andrew Nelson, John K Lodge, Philippa A Jackson, Crystal F Haskell-Ramsay, Fiona L Dodd, Darren Smith, Lewis Cuthbertson, Andrew Nelson, John K Lodge, Philippa A Jackson

Abstract

Background: Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study.

Objectives: The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults.

Methods: This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2).

Results: Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or β diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome.

Conclusions: These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis.

Trial registration: ClinicalTrials.gov NCT03500601.

Keywords: cognition; cognitive function; gut microbiota; healthy adults; metabolomics; mood; nuts.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Schematic of study procedures.
FIGURE 2
FIGURE 2
Participant disposition flow chart.
FIGURE 3
FIGURE 3
Estimated marginal means + SE derived from linear mixed model analysis for picture recognition accuracy (A) and picture recognition reaction time (RT) (B) in nonelderly adults who consumed mixed tree nuts and placebo, each for 4 wk. Significant treatment effect of nuts versus placebo *P <0.05; ***P <0.005.
FIGURE 4
FIGURE 4
Comparison of the number of observed ASVs (Panel A) and Shannon Diversity (Panel B) in stool samples from healthy nonelderly adults between pre- and postmixed nut consumption for 4 wk. Principle co-ordinate analysis with Bray–Curtis dissimilarity between pre (circle) and post (square) intervention samples in healthy nonelderly adults receiving placebo (Panel C) and nuts (Panel D), each for 4 wk. ASV, amplicon sequence variant.
FIGURE 5
FIGURE 5
Comparison of top 10 ASVs showing the greatest difference between groups in the analyses. Pre- and posttreatment data in nonelderly adults who consumed placebo for 4 wk is shown. Wilcoxon analysis revealed no statistical significance between the relative abundance of these populations (Panel A). Comparison of top 10 ASVs showing the greatest difference between groups in the analyses. Pre- and posttreatment data in nonelderly adults who consumed mixed tree nuts for 4 wk. Wilcoxon analysis, False Discovery Rate (FDR) adj. revealed a statistically significance increase in the relative abundance of unclassified Lachnospiraceae (adj.P = 0.015) (Panel B). ASV, amplicon sequence variant.

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