Post-weaning threonine supplementation improves social memory in female offspring exposed to maternal sleep deprivation.

Maternal sleep disturbances are common during late pregnancy and have been associated with long-term neurodevelopmental vulnerability in offspring, but the underlying gut-brain mechanisms remain unclear. Here, we found that late-gestational maternal sleep deprivation (SD) selectively impaired social memory without affecting sociability in adult female offspring. Integrated fecal 16S rRNA sequencing and serum metabolomics identified microbial differences and candidate metabolic changes, including reduced serum L-threonine (Thr). An exploratory cross-condition fecal-transfer experiment revealed parallel behavioral, colonic, and hippocampal patterns in recipient mice, although the design did not permit donor-origin or microbiota-specific causal inference. Given the reduction in circulating Thr and its established role in mucin synthesis, Thr was subsequently evaluated as a candidate intervention. Post-weaning Thr supplementation improved social memory and colonic mucus thickness, whereas these improvements were attenuated by DSS co-treatment. Thr supplementation was also accompanied by attenuation of hippocampal neuroinflammation and recovery of proteins involved in synaptic plasticity. Together, these findings demonstrate that post-weaning Thr supplementation improves social memory in adult female offspring following maternal SD.