Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode

Area of Science:

• Neuroscience
• Developmental Biology
• Nutritional Science

Background:

• Sialylated human milk oligosaccharides (HMOs) are bioactive molecules crucial for infant brain development.
• The specific roles and mechanisms of individual HMOs, like sialyl(alpha2,6)lactose (6'SL), in cognitive programming are not fully understood.
• Sialic acid (Neu5Ac), a component of 6'SL, is vital for forming brain structures that support cognition.

Purpose of the Study:

• To investigate the long-term cognitive and neurobiological consequences of selectively depriving mouse offspring of 6'SL during lactation.
• To elucidate the molecular mechanisms underlying the effects of lactational 6'SL deprivation on brain development and function.

Main Methods:

• Utilized a knockout (KO) mouse model deficient in 6'SL synthesis.
• Cross-fostered wild-type (WT) pups to KO dams to ensure lactational deprivation of 6'SL.
• Assessed cognitive functions (attention, perseveration, memory), hippocampal electrophysiology, plasma metabolomics, gut microbiota, and gene expression in the hippocampus and prefrontal cortex (PFC).

Main Results:

• Lactational 6'SL deprivation led to significant alterations in cognitive functions, hippocampal electrophysiology, and serotonergic system pathways.
• Observed changes in gut microbiota and plasma metabolomics correlated with cognitive and neurological alterations.
• Reduced expression of central nervous system development genes was noted in the PFC at eye-opening, suggesting a critical developmental window.

Conclusions:

• Lactational exposure to 6'SL in maternal milk plays a crucial role in adjusting cognitive development.
• 6'SL appears to influence cognitive maturation by modulating gene expression related to neuronal patterning in the PFC during early development.
• These findings highlight the importance of specific HMOs for optimal neurodevelopment and cognitive function.