The human milk component myo-inositol promotes neuronal connectivity

Authors: PAQUETTE, ANDREW - Yale School Of Medicine; CARBONE, BEATRICE - Tufts Medical Center; VOGEL, SETH - Tufts Medical Center; ISRAEL, ERICA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MARIA, SARAH - Mead Johnson; LABHART, BEAU - Mead Johnson; MORROW, ARDYTHE - University Of Cincinnati College Of Medicine; PHILLIPS, SHAY - Mead Johnson; KUANG, C - Mead Johnson; HONDMANN, DIRK - Mead Johnson; PANDEY, NEERAJ - Mead Johnson; BIEDERER, THOMAS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2023
Publication Date: 7/11/2023
Citation: Paquette, A., Carbone, B.E., Vogel, S., Israel, E., Maria, S.D., Labhart, B., Morrow, A.L., Phillips, S.C., Kuang, C., Hondmann, D., Pandey, N., Biederer, T. 2023. The human milk component myo-inositol promotes neuronal connectivity. Proceedings of the National Academy of Sciences (PNAS). https://doi.org/10.1073/pnas.2221413120.
DOI: https://doi.org/10.1073/pnas.2221413120

Interpretive Summary: The effects of dietary nutrients on the central nervous system, and more specifically, neuronal connectivity, are still in the early stages of understanding. To understand how optimized nutrition during various life stages may enhance brain connectivity, human breast milk samples from multiple global populations were analyzed to identify its naturally occurring key components. Myo-inositol is a component that we found to be highly abundant in human milk during early lactation that also overlaps with the typical timing of neuronal development and formation in the infant brain. Myo-inositol is a sugar alcohol compound that is also naturally found in many fruits, vegetables, and wheat, such as cantaloupe, green peas, and bran products. We found that myo-inositol treatment had an increase in neuronal connections. These results were tested in three different model types including isolated human and rat neurons, in live mice, and in matured brain slices. A potential key nutrient we focused on, myo-inositol, may have important implications of improving neuronal connections during development and throughout maturation in the brain.

Technical Abstract: Effects of micronutrients on brain connectivity are incompletely understood. Analyzing 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 synapse size in the mature cortex. Utilizing an organotypic slice culture system, we additionally determined that myo-inositol is bioactive in mature brain tissue, and treatment of cultured organotypic slices with this carbocyclic sugar increased the number and size of synaptic specializations. 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.