Abstract & Authors:展开
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.
Taylor K Soderborg
Jacob E Friedman
Taylor K Soderborg,Sarah E Clark,Christopher E Mulligan,Rachel C Janssen,Lyndsey Babcock,Diana Ir,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,Jacob E Friedman