Review Article Open Access
Volume 2 | Issue 6 | DOI: https://doi.org/10.33696/immunology.2.061

Maternal Diet Alters Trained Immunity in the Pathogenesis of Pediatric NAFLD

  • 1Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, USA
  • 2Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, USA
  • 3Departments of Physiology and Pediatrics, University of Oklahoma Health Sciences Center, USA
+ Affiliations - Affiliations

Corresponding Author

Jacob E. Friedman, jed-friedman@ouhsc.edu

Received Date: August 17, 2020

Accepted Date: September 21, 2020


Pediatric nonalcoholic fatty liver disease (NAFLD) affects 1 in 10 children in the US, increases risk of cirrhosis and transplantation in early adulthood, and shortens lifespan, even after transplantation. Exposure to maternal obesity and/or a diet high in fat, sugar and cholesterol is strongly associated with development of NAFLD in offspring. However, mechanisms by which “priming” of the immune system in early life increases susceptibility to NAFLD are poorly understood. Recent studies have focused on the role “non-reparative” macrophages play in accelerating inflammatory signals promoting fibrogenesis. In this Commentary, we review evidence that the pioneering gut bacteria colonizing the infant intestinal tract remodel the naïve immune system in the offspring. Epigenetic changes in hematopoietic stem and progenitor cells, induced by exposure to an obesogenic diet in utero, may skew lineage commitment of myeloid cells during gestation. Further, microbial dysbiosis in neonatal life contributes to training innate immune cell responsiveness in the gut, bone marrow, and liver, leading to developmental programming of pediatric NAFLD. Comprehensive understanding of how different gut bacteria and their byproducts shape development of the early innate immune system and microbiome will uncover early interventions to prevent NAFLD pathophysiology.


Pediatric NAFLD, Trained immunity, Pioneering bacteria, Microbiome, Epigenetic reprogramming, Hematopoietic stem cells

Author Information X