Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring

Area of Science:

• Neuroscience
• Microbiology
• Developmental Biology

Background:

• Maternal obesity is linked to neurodevelopmental disorders in offspring.
• Dietary factors during pregnancy can influence offspring neurodevelopment.

Purpose of the Study:

• To investigate the impact of maternal high-fat diet (MHFD) on offspring social behavior and neurobiology.
• To identify the role of gut microbiota in mediating these effects.
• To explore potential therapeutic interventions.

Main Methods:

• Utilized mouse models with maternal high-fat diet (MHFD) and regular diet (MRD).
• Employed co-housing experiments and germ-free mouse colonization.
• Assessed social behavior, gut microbiota composition, synaptic plasticity (LTP) in the ventral tegmental area (VTA), and oxytocin levels.
• Conducted metagenomic analysis and precision microbiota reconstitution.

Main Results:

• MHFD induced social deficits and gut dysbiosis in offspring, which were transferable.
• Social interaction failed to induce LTP in MHFD offspring, who also showed reduced hypothalamic oxytocin.
• A single bacterial strain corrected oxytocin levels, VTA LTP, and social behavior in MHFD offspring.

Conclusions:

• Maternal diet-induced gut microbial imbalance causally links to impaired offspring social behavior and VTA plasticity.
• Targeting the gut microbiota, potentially via probiotics, may offer a therapeutic strategy for neurodevelopmental disorders.