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Nat Commun. 2018 Oct 26;9(1):4462. doi: 10.1038/s41467-018-06929-0.

The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD.

Author information

1
Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
2
Department of Microbiology and Immunology, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
3
Department of Medicine, Division of Infectious Disease, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
4
Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
5
Department of Pediatrics; Allergy and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA.
6
Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainsville, FL, 32610, USA.
7
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
8
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, 80523, CO, USA.
9
Department of Medicine, Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
10
College of Nursing, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
11
Department of Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
12
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
13
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
14
Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA.
15
Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA. jed.friedman@ucdenver.edu.
16
Department of Medicine, Division of Endocrinology, Metabolism & Diabetes, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA. jed.friedman@ucdenver.edu.
17
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Colorado Anschutz Medical Campus, Aurora, 80045, CO, USA. jed.friedman@ucdenver.edu.

Abstract

Maternal obesity is associated with increased risk for offspring obesity and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization of the infant gut by microbes plays a critical role in establishing immunity and metabolic function. Here, we compare germ-free mice colonized with stool microbes (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized mice demonstrate increased hepatic gene expression for endoplasmic reticulum stress and innate immunity together with histological signs of periportal inflammation, a histological pattern more commonly reported in pediatric cases of NAFLD. Inf-ObMB mice show increased intestinal permeability, reduced macrophage phagocytosis, and dampened cytokine production suggestive of impaired macrophage function. Furthermore, exposure to a Western-style diet in Inf-ObMB mice promotes excess weight gain and accelerates NAFLD. Overall, these results provide functional evidence supporting a causative role of maternal obesity-associated infant dysbiosis in childhood obesity and NAFLD.

PMID:
30367045
PMCID:
PMC6203757
DOI:
10.1038/s41467-018-06929-0
[Indexed for MEDLINE]
Free PMC Article

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