Early-life microbiota disruption-induced deficits in the social brain are sensitive to diet.

Diet is one of the major modulators of the microbiota-gut-brain axis across the lifespan. Milk bioactive components, including human milk oligosaccharides such as fucosyllactose and sialyllactose, and prebiotics, including GOS and FOS, promote the viability of commensal bacteria, fortify the intestinal barrier, and improve cognitive development. Here, we investigate the ability of these dietary components alone or in combination to counter the behavioral and physiological effects of early-life microbiota depletion via broad-spectrum antibiotics in mice. Microbiota depletion impaired social recognition in juvenile mice, which was reversed by supplementation with human milk oligosaccharides, GOS/FOS, and their combination. Transcriptomic analysis in brain areas linked to social memory (amygdala and prefrontal cortex), revealed that pathways for central nervous system development, learning, learning and memory are sensitive only to the combined supplementation. Together, our data show that prebiotics and milk bioactive components exert beneficial effects on the host by reversing microbiota depletion-related deficits on the brain and behavior.