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

Nat Commun. 2018 Oct 26;9(1):4462. doi: 10.1038/s41467-018-06929-0.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Animals
  • Bile Acids and Salts / analysis
  • Bile Acids and Salts / metabolism
  • Diet, Western / adverse effects
  • Dysbiosis
  • Fatty Acids, Volatile / analysis
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome* / genetics
  • Germ-Free Life
  • Humans
  • Infant
  • Inflammation / etiology
  • Inflammation / pathology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mothers
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / microbiology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / metabolism
  • Obesity / microbiology*
  • Pregnancy


  • Bile Acids and Salts
  • Fatty Acids, Volatile