A team of researchers has discovered that myo-inositol, a small cyclic sugar molecule found in breast milk – and also in a typical adult diet, including in fruits and grains – plays a crucial role in promoting neuronal connections in infants’ brains, and confirming that what we eat clearly affects brain function.
Prior studies indicated the cognitive benefits of breast milk but were unclear about the specific components responsible, reports Neuroscience News. Myo-inositol was identified in high concentrations in breast milk samples from diverse geographic locations, decreasing over the course of lactation.
This study underscores the importance of breastfeeding in infants’ cognitive development and informs future dietary recommendations, said the researchers.
The presence of myo-inositol is high in early lactation, gradually diminishing over time, and is independent of the mother’s diet, race, and location.
In their study, published in PNAS, the team said that breast milk was not simply sustenance: it was also rich in micronutrients that are critical for healthy brain development in infants.
“The effects of micronutrients on the brain are really under-appreciated,” says Thomas Biederer, PhD, Yale School of Medicine associate professor of neurology and principal investigator. “As a neuroscientist, our findings were stunning to me.”
Prior studies have demonstrated that breast milk is beneficial for the cognitive development of infants, but researchers had little understanding of why. Some proposed that breast milk contains certain unidentified components that provide these benefits.
“Breast milk is rich in bioactive compounds that we are only starting to understand,” says Biederer. “The infant brain is using those compounds to support its developmental processes.”
The starting point of this study was a lead provided by the Biederer lab’s partners at Mead Johnson Nutrition/Reckitt who did a detailed analysis of milk samples donated by mothers at sites in Cincinnati, Mexico City and Shanghai over the course of lactation.
The researchers wanted to study samples from three geographically diverse locations because they hypothesised that the micronutrients present across all samples – independent of diet, race and location – may be of biological significance.
They were especially interested in components that changed over the course of lactation in the same way.
The team noticed that myo-inositol was present in all breast milk samples in high concentrations early on, and gradually diminished over the course of lactation. Importantly, it also had an identical temporal profile across all three sites.
“The molecule is very robustly controlled by the mother,” says Biederer. Intrigued, they examined the effects of myo-inositol on the developing brain using a variety of models, including cultured human neurons and cultured brain tissue.
They found that the sugar molecule boosted synapse abundance in the neurons and enhanced neuronal connectivity.
“Our study demonstrates that breast milk is extremely valuable in how mothers can support the formation of connections in an infant’s brain,” says Biederer.
“It truly shows the importance of valuing the complexity of breast milk. It’s not just a source of calories, but an extremely rich, complex biofluid, and the mother’s body is really attuned to changing the composition of breast milk to match what the infant needs at different stages of development.”
These results can guide dietary recommendations for paediatric nutrition. The findings also emphasise the importance of having policies that support breastfeeding mothers, says Biederer, because these “will help benefit society as a whole”.
The current study focuses on the production of connections in the brain, a hallmark of the first months after birth. After these connections are established, the brain then works to refine and optimise these connections.
In future studies, Biederer would like to explore how breast milk supports infants during this later stage of development.
“Refinement is a critical process for creating the right patterns in the brain,” he says. “Studying this stage will be as important, if not more important, than studying the initial formation of connections.”
Study details
The human milk component myo-inositol promotes neuronal connectivity
Andrew Paquette, Beatrice Carbone, Seth Vogel, and Thomas Biederer.
Published in PNAS on 11 July 2023
Significance
The roles of micronutrients and bioactive dietary compounds in neuronal wiring are only beginning to be addressed. This study reveals substantial benefits of the human milk component myo-inositol for developing synapses across species, including in human neurons. These findings demonstrate that myo-inositol promotes neuronal connectivity and can guide dietary recommendations across life stages. This can be significant for paediatric nutrition and the improvement of infant formulas in under-resourced areas with conditions that prevent sufficient breastfeeding. Moreover, this carbocyclic sugar can promote synapse density in mature brain tissue.
Abstract
Effects of micronutrients on brain connectivity are incompletely understood. Analysing human milk samples across global populations, we identified the carbocyclic sugar myo-inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. Myo-inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner.
Mechanistically, myo-inositol enhanced the ability of neurons to respond to trans-synaptic interactions that induce synapses. Effects of myo-inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilising an organotypic slice culture system, we additionally determined that myo-inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specialisations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies myo-inositol as a breast milk component that promotes the formation of neuronal connections.
PNAS article – The human milk component myo-inositol promotes neuronal connectivity (Open access)
Neuroscience News article – Breast milk component boosts infant connectivity (Open access)
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