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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...

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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
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author 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.
author_facet 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.
author_sort Soderborg, Taylor K.
collection PubMed
description 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.
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spelling pubmed-62037572018-10-29 The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD 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. Nat Commun Article 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. Nature Publishing Group UK 2018-10-26 /pmc/articles/PMC6203757/ /pubmed/30367045 http://dx.doi.org/10.1038/s41467-018-06929-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
title The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
title_full The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
title_fullStr The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
title_full_unstemmed The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
title_short The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD
title_sort gut microbiota in infants of obese mothers increases inflammation and susceptibility to nafld
topic Article
url 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
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