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

  • Dharti Shantaram
  • , Rebecca Hoyd
  • , Alecia M. Blaszczak
  • , Linda Antwi
  • , Anahita Jalilvand
  • , Valerie P. Wright
  • , Joey Liu
  • , Alan J. Smith
  • , David Bradley
  • , William Lafuse
  • , Yun Zhou Liu
  • , Nyelia F. Williams
  • , Owen Snyder
  • , Caroline Wheeler
  • , Bradley Needleman
  • , Stacy Brethauer
  • , Sabrena Noria
  • , David Renton
  • , Kyle A. Perry
  • , Prabha Nagareddy
  • Daniel Wozniak, Sahil Mahajan, Pranav S.J.B. Rana, Maciej Pietrzak, Larry S. Schlesinger, Daniel J. Spakowicz, Willa A. Hsueh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number5434
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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