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

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.

SUBMITTER: Soderborg TK

PROVIDER: S-EPMC6203757 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Soderborg Taylor K TK Clark Sarah E SE Mulligan Christopher E CE Janssen Rachel C RC Babcock Lyndsey L Ir Diana D Young Bridget B Krebs Nancy N Lemas Dominick J DJ Johnson Linda K LK Weir Tiffany T Lenz Laurel L LL Frank Daniel N DN Hernandez Teri L TL Kuhn Kristine A KA D'Alessandro Angelo A Barbour Linda A LA El Kasmi Karim C KC Friedman Jacob E JE

Nature communications 20181026 1

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 hepat ...[more]

PMID: 30367045

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Project description:BackgroundHuman milk and infant gut microbiota are essential for the immune system maturation and protection against infections. There is scarce information on the microbiological composition of breast milk in general, and none from developing countries. The objective of the study was to characterize the breast milk and gut microbiota from mothers and infants from southern Mozambique, where infections and breastfeeding are prevalent.MethodsA community-based study was undertaken among 121 pairs of women and infants. Breast milk and infant's faeces were analyzed by bacterial culture and molecular methods. Breast milk samples were screened for HIV RNA by RT-PCR.ResultsThe most frequent bacterial groups isolated by culture media in breast milk were Staphylococci (96.4%), Streptococci (92.7%) and Lactobacilli (56.4%). HIV RNA was detected in 24% of the samples. Staphylococcus hominis, S. aureus, and S.parasanguis were more frequently isolated in infants ?14 days of life. Women on exclusive breastfeeding presented higher proportion of S. parasanguis in breast milk than those on mixed infant feeding (36.4% versus 11.1%, p?=?0.035). Bacterial diversity (mean number of bacterial species isolated by sample: 10.4 versus 8.5; p?=?0.004) and the frequency of Lactobacillus spp (75.9% versus 36%, p?=?0.003) were higher in the specimens with HIV RNA than in those without it. The main bacterial groups found in infant's faeces were Bifidobacterium, Streptococci and Enterococci.ConclusionsWomen with HIV RNA in breast milk had a different pattern of microbiological composition, suggesting specific immunopathological phenomena in HIV-infected women. Both breast milk and faecal microbiota composition varied with lactation period, which might be related to changes in the type of feeding over time and/or in the milk's biochemical characteristics. These findings provide insights into interactions between commensal bacteria and HIV infection in human milk and the role of these bacteria in mucosal protection against infections in breastfed infants.

Dataset Information

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

Publications

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

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