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

## TL;DR

Early-life disruption of gut microbes harms social behavior in mice, but this can be reversed with specific dietary components like human milk sugars and prebiotics.

## Contribution

The study shows that combining human milk oligosaccharides with prebiotics more effectively reverses microbiota depletion effects on the brain and behavior.

## Key findings

- HMOs and GOS/FOS reversed social behavior deficits caused by early-life microbiota depletion.
- Combined supplementation restored brain pathways related to learning and memory more effectively than individual components.
- Microbiota enzymatic genes for carbohydrate utilization were restored with HMOs and GOS/FOS.

## Abstract

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.

•HMOs and GOS/FOS rescue social behaviour deficits induced by early-life microbiota depletion•HMOs and GOS/FOS restored the abundance of microbiota enzymatic genes for carbohydrate utilization•HMOs and GOS/FOS restored myelination and learning and memory pathways in the juvenile mouse brain•Combining HMOs with GOS/FOS restores microbiota, brain and behaviour more effectively than alone

HMOs and GOS/FOS rescue social behaviour deficits induced by early-life microbiota depletion

HMOs and GOS/FOS restored the abundance of microbiota enzymatic genes for carbohydrate utilization

HMOs and GOS/FOS restored myelination and learning and memory pathways in the juvenile mouse brain

Combining HMOs with GOS/FOS restores microbiota, brain and behaviour more effectively than alone

Neuroscience; Microbiology; Microbiome