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

Taylor K. Soderborg, Sarah E. Clark, Christopher E. Mulligan, Rachel C. Janssen, Lyndsey Babcock, Diana Ir, Bridget Young, Nancy Krebs, Dominick J. Lemas, Linda K. Johnson, Tiffany Weir, Laurel L. Lenz, Daniel N. Frank, Teri L. Hernandez, Kristine A. Kuhn, Angelo D’Alessandro, Linda A. Barbour, Karim C. El Kasmi and Jacob E. Friedman ()
Additional contact information
Taylor K. Soderborg: University of Colorado Anschutz Medical Campus
Sarah E. Clark: University of Colorado Anschutz Medical Campus
Christopher E. Mulligan: University of Colorado Anschutz Medical Campus
Rachel C. Janssen: University of Colorado Anschutz Medical Campus
Lyndsey Babcock: University of Colorado Anschutz Medical Campus
Diana Ir: University of Colorado Anschutz Medical Campus
Bridget Young: University of Colorado Anschutz Medical Campus
Nancy Krebs: University of Colorado Anschutz Medical Campus
Dominick J. Lemas: University of Colorado Anschutz Medical Campus
Linda K. Johnson: University of Colorado Anschutz Medical Campus
Tiffany Weir: Colorado State University
Laurel L. Lenz: University of Colorado Anschutz Medical Campus
Daniel N. Frank: University of Colorado Anschutz Medical Campus
Teri L. Hernandez: University of Colorado Anschutz Medical Campus
Kristine A. Kuhn: University of Colorado Anschutz Medical Campus
Angelo D’Alessandro: University of Colorado Anschutz Medical Campus
Linda A. Barbour: University of Colorado Anschutz Medical Campus
Karim C. El Kasmi: University of Colorado Anschutz Medical Campus
Jacob E. Friedman: University of Colorado Anschutz Medical Campus

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06929-0

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