1. Epidemiology and Global Health
  2. Immunology and Inflammation
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Contrasting effects of Western vs. Mediterranean diets on monocyte inflammatory gene expression and social behavior in a primate model

  1. Corbin SC Johnson
  2. Carol Shively
  3. Kristofer T Michalson
  4. Amanda J Lea
  5. Ryne J DeBo
  6. Timothy D Howard
  7. Gregory A Hawkins
  8. Susan E Appt
  9. Yongmei Liu
  10. Charles E McCall
  11. David M Herrington
  12. Edward H Ip
  13. Thomas C Register
  14. Noah Snyder-Mackler  Is a corresponding author
  1. University of Washington, United States
  2. Wake Forest School of Medicine, United States
  3. Princeton University, United States
  4. Duke University School of Medicine, United States
  5. Arizona State University, United States
Research Article
  • Cited 1
  • Views 1,573
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Cite this article as: eLife 2021;10:e68293 doi: 10.7554/eLife.68293

Abstract

Dietary changes associated with industrialization substantially increase the prevalence of chronic diseases, such as obesity, type II diabetes, and cardiovascular disease, major contributors to the public health burden. The high prevalence of these chronic diseases is often attributed to an 'evolutionary mismatch' between human physiology and modern nutritional environments. Western diets enriched with foods that were scarce throughout human evolutionary history (e.g., simple sugars and saturated fats) promote inflammation and disease relative to diets more akin to ancestral human hunter-gatherer diets, such as a Mediterranean diet. Peripheral blood monocytes, precursors to macrophages and important mediators of innate immunity and inflammation, are sensitive to the environment and may represent a critical intermediate in the pathway linking diet to disease. We evaluated the effects of 15 months of whole diet manipulations mimicking human Western or Mediterranean diet patterns on monocyte polarization using a well-established model of human health, the cynomolgus macaque (Macaca fascicularis). Monocyte transcriptional profiles differed markedly between the two diets, with 40% of transcripts showing differential expression (FDR < 0.05). Monocytes from Western diet consumers were polarized toward a more proinflammatory phenotype. Compared to the Mediterranean diet, the Western diet shifted the co-expression of 445 gene pairs, including small RNAs and transcription factors associated with metabolism and adiposity in humans, and dramatically altered behavior. For example, Western-fed individuals were more anxious and less socially integrated compared to the Mediterranean-fed subjects. These behavioral changes were also associated with some of the effects of diet on gene expression, suggesting an interaction between diet, central nervous system activity, and monocyte gene expression. The results of this study provide new insights into evolutionary mismatch at the molecular level and uncover new pathways through which Western diets alter monocyte polarization toward a proinflammatory phenotype.

Data availability

Sequencing data have been deposited in GEO under accession code GSE144314.Code can be found here: https://github.com/cscjohns/diet_behavior_immunity

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Corbin SC Johnson

    Department of Psychology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9616-5755
  2. Carol Shively

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kristofer T Michalson

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amanda J Lea

    Lewis-Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8827-2750
  5. Ryne J DeBo

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Timothy D Howard

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Gregory A Hawkins

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Susan E Appt

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Yongmei Liu

    Division of Cardiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Charles E McCall

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. David M Herrington

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Edward H Ip

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Thomas C Register

    Wake Forest School of Medicine, Winston-Salem, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Noah Snyder-Mackler

    Center for Evolution & Medicine, School of Life Sciences, Arizona State University, Tempe, United States
    For correspondence
    nsnyderm@asu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3026-6160

Funding

National Heart, Lung, and Blood Institute (R01HL087103)

  • Carol Shively

National Heart, Lung, and Blood Institute (R01HL122393)

  • Carol Shively
  • Thomas C Register

National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097748)

  • Thomas C Register

National Institute on Aging (R00AG051764)

  • Noah Snyder-Mackler

National Institute on Aging (R01AG060931)

  • Noah Snyder-Mackler

Wake Forest School of Medicine

  • Carol Shively

Helen Hay Whitney Foundation

  • Amanda J Lea

National Cancer Institute (P30CA012197)

  • Carol Shively
  • Timothy D Howard
  • Gregory A Hawkins
  • Susan E Appt
  • Charles E McCall
  • David M Herrington
  • Edward H Ip
  • Thomas C Register

National Institutes of Health (S10OD023409)

  • Gregory A Hawkins

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal manipulations were performed according to the guidelines of state and federal laws, the US Department of Health and Human Services, and the Animal Care and Use Committee of Wake Forest School of Medicine (ACUC #A12-195; #A15-180).

Reviewing Editor

  1. Imroze Khan, Ashoka University, India

Publication history

  1. Preprint posted: January 28, 2020 (view preprint)
  2. Received: March 11, 2021
  3. Accepted: July 28, 2021
  4. Accepted Manuscript published: August 2, 2021 (version 1)
  5. Version of Record published: September 7, 2021 (version 2)

Copyright

© 2021, Johnson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

    1. Evolutionary Biology
    2. Epidemiology and Global Health
    3. Microbiology and Infectious Disease
    4. Genetics and Genomics
    Edited by George H Perry et al.
    Collection

    eLife is pleased to present a Special Issue to highlight recent advances in the growing and increasingly interdisciplinary field of evolutionary medicine.

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