Abstract
The effects of diet and nutrition extend beyond individual health: food intake before conception or during pregnancy and lactation can affect the health of offspring. Diet is one of the most powerful modulators of the gut microbiome, influencing gene–environment interactions, with several emerging mechanisms pointing to the microbiome–metabolite–epigenome axis. In this Review, we discuss the effect of dietary changes on the gametes (‘gut–germline axis’) or in utero (‘gut–neonatal axis’) that may change the predisposition of offspring to several non-communicable diseases. Examples of diets discussed are those that detrimentally modulate the parental microbiota and lead to epigenetic changes in the progeny, including Western diets characterized by high saturated fat and low protein or fibre intake. We summarize studies using animal models, which suggest that these diets can have long-lasting effects on the offspring microbiome, epigenome and phenotype, particularly across the cardiometabolic and immune systems, and discuss the limitations of current studies as well as future directions for the field. Translational research investigating the benefits of parental dietary interventions before and during pregnancy, mainly using personalized approaches, is needed. This would, in turn, reduce rates of non-communicable diseases in generations to come.
Key points
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Maternal diet during pregnancy and lactation can shape offspring health by influencing the gut microbiota and epigenetic programming, contributing to the long-term risk of non-communicable diseases.
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Fetal development is likely influenced by maternal microbial metabolites, rather than live microorganisms, that might cross the placenta; however, birth mode and maternal diet can shape early-life microbiota and epigenetic programming.
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Maternal intake of methyl-donor nutrients such as choline influences offspring epigenetics via gut microbial metabolism, linking diet to neurodevelopment and long-term health outcomes.
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Maternal protein, fat and fibre intake during pregnancy modulates offspring microbiota and epigenetics, influencing immune, metabolic and cognitive outcomes through metabolites such as short-chain fatty acids.
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Paternal gut microbiota and diet influence sperm epigenetics and offspring health, supporting a gut–germline axis that links paternal exposures to metabolic and behavioural outcomes in offspring.
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Despite promising findings, most evidence to link parental diet, gut microbiota and epigenetics to offspring health is from animal studies, highlighting the need for human data, which is likely to require personalized approaches.
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Acknowledgements
F.Z.M. is supported by a Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation, a National Heart Foundation Future Leader Fellowship (105663), a National Health & Medical Research Council (NHMRC) Emerging Leader Fellowship (GNT2017382), and a grant from the Australian Research Council (DP230102725). A.E.-O. is supported by a fellowship from the NHMRC (GTN1154650) and NHMRC – CTCS (2014763). M.S. is supported by a National Heart Foundation Postdoctoral Fellowship (106698).
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C.Y. and F.Z.M. conceived, designed and drafted most of the article. C.Y. and M.S. created the initial draft of the figures. M.S. and A.E.-O. provided critical feedback and drafted some sections.
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Yang, C., Snelson, M., El-Osta, A. et al. Parental diet and offspring health: a role for the gut microbiome via epigenetics. Nat Rev Gastroenterol Hepatol (2025). https://doi.org/10.1038/s41575-025-01106-3
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DOI: https://doi.org/10.1038/s41575-025-01106-3
