Format

Send to

Choose Destination
FASEB J. 2019 May;33(5):6456-6469. doi: 10.1096/fj.201802477R. Epub 2019 Feb 15.

Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.

Author information

1
Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
2
Biomedical Informatics, Center for Clinical and Translational Sciences, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
3
Department of Anesthesiology and Perioperative Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
4
Department of Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
5
Department of Biology, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
6
Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine (CRNH) Auvergne, Université Clermont Auvergne, Clermont-Ferrand, France.
7
Unité Mixte de Recherche (UMR) 247, Institut des Biomolécules Max Mousseron (IBMM), Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), University of Montpellier, Montpellier, France.

Abstract

Calorie-dense obesogenic diet (OBD) is a prime risk factor for cardiovascular disease in aging. However, increasing age coupled with changes in the diet can affect the interaction of intestinal microbiota influencing the immune system, which can lead to chronic inflammation. How age and calorie-enriched OBD interact with microbial flora and impact leukocyte profiling is currently under investigated. Here, we tested the interorgan hypothesis to determine whether OBD in young and aging mice alters the gut microbe composition and the splenic leukocyte profile in acute heart failure (HF). Young (2-mo-old) and aging (18-mo-old) mice were supplemented with standard diet (STD, ∼4% safflower oil diet) and OBD (10% safflower oil) for 2 mo and then subjected to coronary artery ligation to induce myocardial infarction. Fecal samples were collected pre- and post-diet intervention, and the microbial flora were analyzed using 16S variable region 4 rRNA gene DNA sequencing and Quantitative Insights Into Microbial Ecology informatics. The STD and OBD in aging mice resulted in an expansion of the genus Allobaculum in the fecal microbiota. However, we found a pathologic change in the neutrophil:lymphocyte ratio in aging mice in comparison with their young counterparts. Thus, calorie-enriched OBD dysregulated splenic leukocytes by decreasing immune-responsive F4/80+ and CD169+ macrophages in aging mice. OBD programmed neutrophil swarming with an increase in isoprostanoid levels, with dysregulation of lipoxygenases, cytokines, and metabolite-sensing receptor expression. In summary, calorie-dense OBD in aging mice disrupted the composition of the gut microbiome, which correlates with the development of integrative and system-wide nonresolving inflammation in acute HF.-Kain, V., Van Der Pol, W., Mariappan, N., Ahmad, A., Eipers, P., Gibson, D. L., Gladine, C., Vigor, C., Durand, T., Morrow, C., Halade, G. V. Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.

KEYWORDS:

inflammation; leukocytes; myocardial infarction; nonresolving inflammation; resolution of inflammation

PMID:
30768364
PMCID:
PMC6463911
[Available on 2020-02-15]
DOI:
10.1096/fj.201802477R

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center