Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Soderborg, Taylor K., Clark, Sarah E., Mulligan, Christopher E., Janssen, Rachel C., Babcock, Lyndsey, Ir, Diana, Young, Bridget, Krebs, Nancy, Lemas, Dominick J., Johnson, Linda K., Weir, Tiffany, Lenz, Laurel L., Frank, Daniel N., Hernandez, Teri L., Kuhn, Kristine A., D’Alessandro, Angelo, Barbour, Linda A., El Kasmi, Karim C., Friedman, Jacob E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203757/
https://www.ncbi.nlm.nih.gov/pubmed/30367045
http://dx.doi.org/10.1038/s41467-018-06929-0
Descripción
Sumario: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.