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Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and
Anna Ratsika1, Martin G Codagnone1, Thomaz F S Bastiaanssen1
1APC Microbiome Ireland, Biosciences Institute, University College Cork, Cork T12YT20, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork T12YT20, Ireland.
Insights
Maternal high-fat diet alters gut microbes, affecting offspring brain development and behavior. This diet impacts neurodevelopment, leading to lasting behavioral changes and altered brain metabolism in offspring.
Area of Science:
- Neuroscience
- Developmental Biology
- Microbiology
Background:
- The developing brain is sensitive to maternal nutrition during the perinatal period.
- Gut microbiota influences neurodevelopment and behavior.
- Maternal obesity is linked to offspring neurodevelopmental and affective disorders.
Purpose of the Study:
- To investigate how maternal high-fat diet (mHFD) impacts offspring brain development, neuroimmune signals, and behavior into adolescence.
- To understand the role of maternal gut microbiota changes in mediating these effects.
Main Methods:
- Comparison of maternal caecal microbiota composition in response to diet.
- Analysis of maternal plasma and embryonic brain metabolomics.
- Assessment of offspring behavior and gene expression during adolescence.
Main Results:
- Maternal diet significantly altered maternal gut microbiota composition.
- mHFD increased microbial genes linked to quinolinic acid synthesis and kynurenine levels in maternal plasma.
- Offspring brains showed altered glutamate metabolism markers; adolescent offspring displayed sex-dependent behavioral changes and upregulated glutamate-related genes.
Conclusions:
- Maternal high-fat diet induces lasting changes in offspring neurodevelopment, behavior, and brain metabolism.
- Microbiota-derived signals play a role in mediating the effects of maternal diet on offspring neurodevelopment.
- Glutamate signaling pathways are implicated in the observed neurodevelopmental and behavioral alterations.
Abstract:
The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.
