From Maternal Diet to Neurodevelopmental Disorders: A Story of Neuroinflammation.

Maude Bordeleau,M Mallar Chakravarty,Lourdes Fernández De Cossío,Marie-Ève Tremblay

doi:10.3389/fncel.2020.612705

Abstract

Providing the appropriate quantity and quality of food needed for both the mother’s well-being and the healthy development of the offspring is crucial during pregnancy. However, the macro- and micronutrient intake also impacts the body’s regulatory supersystems of the mother, such as the immune, endocrine, and nervous systems, which ultimately influence the overall development of the offspring. Of particular importance is the association between unhealthy maternal diet and neurodevelopmental disorders in the offspring. Epidemiological studies have linked neurodevelopmental disorders like autism spectrum disorders, attention-deficit-hyperactivity disorder, and schizophrenia, to maternal immune activation (MIA) during gestation. While the deleterious consequences of diet-induced MIA on offspring neurodevelopment are increasingly revealed, neuroinflammation is emerging as a key underlying mechanism. In this review, we compile the evidence available on how the mother and offspring are both impacted by maternal dietary imbalance. We specifically explore the various inflammatory and anti-inflammatory effects of dietary components and discuss how changes in inflammatory status can prime the offspring brain development toward neurodevelopmental disorders. Lastly, we discuss research evidence on the mechanisms that sustain the relationship between maternal dietary imbalance and offspring brain development, involving altered neuroinflammatory status in the offspring, as well as genetic to cellular programming notably of microglia, and the evidence that the gut microbiome may act as a key mediator.

Highlights

Nutrition is essential to the maintenance of life, but it is fundamental at the onset of life during the antenatal and early life periods of growth and development of organs and systems
Across the world, ∼39 million pregnant women are estimated to be obese [body mass index (BMI) over 30] or overweight (BMI: between 25 and 30) due to poor nutrition (Chen et al, 2018), ∼32 million of pregnant women are anemic, ∼19 million of pregnant women suffer from vitamin A deficiency, while millions of pregnant women suffer from iron, folate, zinc, and/or iodine intake deficiency (Garcia−Casal et al, 2018)
Protein is a macronutrient that has long been associated with impairing brain growth and having broad neurocognitive effects (Monk et al, 2013). Another macronutrient: fat, is known to have important effects on neurodevelopment as components of omega-6 and omega-3 fatty acids (PUFAs) are necessary parts of neural cell membranes, and supplementation during pregnancy in controlled human trials showed better neurocognitive performance in the children (Helland et al, 2003), supplementation with poly-unsaturated fatty acids (PUFAs) was inconclusive in a meta-analysis looking at nutrition impacts on autism spectrum disorder (ASD), attention-deficithyperactivity disorder (ADHD), and intellectual disability (Li et al, 2019)

Summary

Introduction

Nutrition is essential to the maintenance of life, but it is fundamental at the onset of life during the antenatal and early life periods of growth and development of organs and systems. In the context of maternal immune activation (MIA), a postnatal ketogenic diet in the offspring demonstrates a protective effect (Ruskin et al, 2017b); it remains to be investigated if this protective effect on the postnatal brain is due to anti-inflammatory and metabolic modulation by the ketones and/or acting via the gut microbiome (Ang et al, 2020).

Results

Conclusion