Maternal high-fat diet results in microbiota-dependent expansion of ILC3s in mice offspring
Sarah Thomas Babu, … , Lora V. Hooper, Julie Mirpuri
Sarah Thomas Babu, … , Lora V. Hooper, Julie Mirpuri
Published October 4, 2018
Citation Information: JCI Insight. 2018;3(19):e99223. https://doi.org/10.1172/jci.insight.99223.
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Research Article Immunology Inflammation

Maternal high-fat diet results in microbiota-dependent expansion of ILC3s in mice offspring

Abstract

Maternal obesity and a high-fat diet (HFD) during the perinatal period have documented short- and long-term adverse outcomes for offspring. However, the mechanisms of maternal HFD effects on neonatal offspring are unclear. While the effects of maternal HFD exposure during pregnancy on the offspring are increasingly being appreciated, we do not know if maternal HFD alters the microbiota or affects neonatal susceptibility to inflammatory conditions, nor the mechanisms involved. In this study, we show that the offspring of mothers exposed to HFD develop a unique microbiota, marked by expansion of Firmicutes, and an increase in IL-17–producing type 3 innate lymphoid cells (ILC3s). The expansion of ILC3s was recapitulated through neocolonization with HFD microbiota alone. Further, the HFD offspring were susceptible to a neonatal model of inflammation that was reversible with IL-17 blockade. Collectively, these data suggest a previously unknown and unique role for ILC3s in the promotion of an early inflammatory susceptibility in the offspring of mothers exposed to HFD.

Authors

Sarah Thomas Babu, Xinying Niu, Megan Raetz, Rashmin C. Savani, Lora V. Hooper, Julie Mirpuri

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Figure 1

HFD offspring have an altered microbiota and increased expression and production of IL-17.

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HFD offspring have an altered microbiota and increased expression and pr...
(A) Heatmap of the relative abundance of the most dominant genera in the fecal colonic contents of 1-week-old mice as determined by genomic DNA analysis by next-generation sequencing. HFD offspring and RD offspring are representative of 3 mice in each group. (B) Pie chart showing the proportion of Bacilli, Gammaproteobacteria, Bacteroidia, Mollicutes, and Clostridia seen in 1-week- and (C) 3-week-old mice analyzed by next-generation sequencing in RD/RD, HFD/HFD, and HFD/RD offspring. Percentages are representative of populations of Bacilli (Firmicutes). (D) Expression of IL-17A, MIP-2, IL-1β, and TNF-α was analyzed by quantitative real-time PCR (log scale) in small intestine from 1-week- and (E) 3-week-old mice. (F) ELISA showing production of IL-17A (μg/μl) in small intestine of RD/RD and HFD/HFD mice. RD/RD represent RD offspring cross-fostered to RD mothers at birth. HFD/HFD represents HFD offspring cross-fostered to HFD mothers at birth. HFD/RD represents HFD offspring cross-fostered to RD mothers at birth. The data shown are representative of 3 experiments with 6–10 mice in each group. Data are depicted as the mean ± SEM. *P < 0.05; **P < 0.01 by 1-way ANOVA with Tukey’s post hoc test (D and E) or 2-tailed Student’s t test (F). HFD, high-fat diet; RD, regular diet; ns, not significant.