Maternal high-fat diet linked to inflammatory outcomes in offspring
Maternal obesity has been associated with adverse outcomes in offspring; however, it is not clear how maternal obesity or high-fat diet (HFD) impart long-term effects on offspring. In this episode, Julie Mirpuri and colleagues use murine models to evaluate the effects of HFD during pregnancy on offspring. The offspring of HFD-fed mothers developed a microbiome that was distinctly different than that of offspring of mothers on a regular diet. Moreover, IL-17–producing type 3 innate lymphoid cells (ILC3s) were increased the offspring of HFD-fed mothers, a phenotype linked to the HFD-associated microbiota. The offspring of HFD-fed mothers were also more susceptible to necrotizing enterocolitis. Together, these results indicate that maternal HFD influences the offspring microbiome, thereby increasing ILC3s and susceptibility to inflammatory insult.
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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
