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Maternal Diet Alters Trained Immunity in the Pathogenesis of Pediatric NAFLD
Karen R Jonscher1,2, Jesse Abrams2, Jacob E Friedman2,3
1Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, USA.
Insights
Early life gut bacteria and maternal diet influence pediatric nonalcoholic fatty liver disease (NAFLD) by shaping the developing immune system. Understanding these interactions is key to preventing NAFLD.
Area of Science:
- Immunology
- Microbiology
- Pediatric Gastroenterology
Background:
- Pediatric nonalcoholic fatty liver disease (NAFLD) affects 1 in 10 US children, increasing risks of cirrhosis and early mortality.
- Maternal obesity and diet are linked to NAFLD in offspring, but immune system priming mechanisms are unclear.
- Non-reparative macrophages are implicated in accelerating inflammatory signals that promote liver fibrogenesis.
Purpose of the Study:
- To review evidence on how early-life gut bacteria and maternal diet influence immune system development and pediatric NAFLD susceptibility.
- To explore the role of epigenetic changes and microbial dysbiosis in programming NAFLD pathophysiology.
Main Methods:
- Review of existing scientific literature on gut microbiome, immune system development, epigenetics, and NAFLD.
- Analysis of how maternal diet and early microbial colonization impact immune cell lineage commitment and responsiveness.
Main Results:
- Pioneering gut bacteria colonizing infants can remodel the naive immune system.
- In utero obesogenic diet exposure may induce epigenetic changes skewing myeloid cell development.
- Neonatal microbial dysbiosis trains innate immune cell responses, contributing to NAFLD programming.
Conclusions:
- Early-life gut microbiome and immune system interactions are critical in pediatric NAFLD development.
- Understanding these mechanisms can reveal novel targets for early intervention and prevention strategies.
- Further research into specific bacterial byproducts and their impact on early immune development is warranted.
Abstract:
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.
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