Journal Article

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

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

2024

Overview

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. The role of neutrophils is increasingly being recognized in chronic inflammation and metabolic disorders. Here the authors show that visceral adipose tissue from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38 / 38/61 / 45 / 631/250/2152 / 631/326/2565 / 631/443/319/1642/393 / 82/51 / 82/80 / Adipose tissue / Animals / Bacteria / Body fat / CD4 antigen / Colon cancer / Colorectal cancer / Diet / Diet, High-Fat - adverse effects / Feces - microbiology / Female / Firing pattern / Gastrointestinal Microbiome - immunology / Gene expression / High fat diet / Human tissues / Humanities and Social Sciences / Humans / Immunoregulation / Inflammation / Inflammation - immunology / Inflammation - microbiology / Inflammation - pathology / Insulin resistance / Intra-Abdominal Fat - immunology / Intra-Abdominal Fat - metabolism / Leukocytes (neutrophilic) / Lymphocytes / Lymphocytes T / Male / Metabolic disorders / Mice / Mice, Inbred C57BL / Microbiomes / Microbiota - immunology / multidisciplinary / Neutrophil Infiltration / Neutrophilia / Neutrophils / Neutrophils - immunology / Obesity / Obesity - immunology / Obesity - microbiology / Science / Science (multidisciplinary) / Th1 Cells - immunology / Therapeutic targets