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Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils

Author

Listed:
  • Dharti Shantaram

    (Wexner Medical Center at The Ohio State University)

  • Rebecca Hoyd

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Alecia M. Blaszczak

    (Wexner Medical Center at The Ohio State University)

  • Linda Antwi

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Anahita Jalilvand

    (Wexner Medical Center at The Ohio State University)

  • Valerie P. Wright

    (Wexner Medical Center at The Ohio State University)

  • Joey Liu

    (Wexner Medical Center at The Ohio State University)

  • Alan J. Smith

    (Wexner Medical Center at The Ohio State University)

  • David Bradley

    (Wexner Medical Center at The Ohio State University)

  • William Lafuse

    (The Ohio State University)

  • YunZhou Liu

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Nyelia F. Williams

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Owen Snyder

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Caroline Wheeler

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Bradley Needleman

    (The Ohio State University)

  • Stacy Brethauer

    (The Ohio State University)

  • Sabrena Noria

    (The Ohio State University)

  • David Renton

    (The Ohio State University)

  • Kyle A. Perry

    (The Ohio State University)

  • Prabha Nagareddy

    (Cardiovascular Section University of Oklahoma Health Sciences Center (OUHSC))

  • Daniel Wozniak

    (The Ohio State University)

  • Sahil Mahajan

    (The Ohio State University)

  • Pranav S. J. B. Rana

    (The Ohio State University)

  • Maciej Pietrzak

    (The Ohio State University)

  • Larry S. Schlesinger

    (Texas Biomedical Research Institute)

  • Daniel J. Spakowicz

    (Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute)

  • Willa A. Hsueh

    (Wexner Medical Center at The Ohio State University)

Abstract

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.

Suggested Citation

  • Dharti Shantaram & Rebecca Hoyd & Alecia M. Blaszczak & Linda Antwi & Anahita Jalilvand & Valerie P. Wright & Joey Liu & Alan J. Smith & David Bradley & William Lafuse & YunZhou Liu & Nyelia F. Willia, 2024. "Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48935-5
    DOI: 10.1038/s41467-024-48935-5
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    References listed on IDEAS

    as
    1. Justin I. Odegaard & Roberto R. Ricardo-Gonzalez & Matthew H. Goforth & Christine R. Morel & Vidya Subramanian & Lata Mukundan & Alex Red Eagle & Divya Vats & Frank Brombacher & Anthony W. Ferrante & , 2007. "Macrophage-specific PPARγ controls alternative activation and improves insulin resistance," Nature, Nature, vol. 447(7148), pages 1116-1120, June.
    2. Ivan Vujkovic-Cvijin & Jack Sklar & Lingjing Jiang & Loki Natarajan & Rob Knight & Yasmine Belkaid, 2020. "Host variables confound gut microbiota studies of human disease," Nature, Nature, vol. 587(7834), pages 448-454, November.
    3. David Bradley & Alan J. Smith & Alecia Blaszczak & Dharti Shantaram & Stephen M. Bergin & Anahita Jalilvand & Valerie Wright & Kathleen L. Wyne & Revati S. Dewal & Lisa A. Baer & Katherine R. Wright &, 2022. "Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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