NeuropharmacologyJul 13, 2026

Prenatal Bifidobacterium bifidum may reduce early-life stress effects on behavior by lowering brain inflammation in offspring mice

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 14, 2026

Abstract

Maternal Bifidobacterium bifidum intervention rescued growth retardation and social deficits in offspring exposed to early-life stress.

Early-life stress is linked to neurobehavioral abnormalities and gut-brain axis disruption in offspring.
Maternal separation in mice was used to model early-life stress effects on development.
Probiotic treatment with Bifidobacterium bifidum improved behavioral performance in offspring.
The intervention also altered gut microbiota composition and reduced inflammatory markers in various tissues.
5'-methylthioadenosine, a microbial metabolite, was associated with alleviating neurobehavioral issues linked to early-life stress.

Simplified

Early-life stress is a key environmental risk factor for neurobehavioral abnormalities in offspring, which disrupts gut-brain axis homeostasis and causes neurodevelopmental damage. Probiotics have shown important potential in improving neurodevelopmental abnormalities. As a dominant gut microbe in healthy mother-infant pairs, Bifidobacterium bifidum is closely related to neurobehavioral abnormalities. This study aimed to explore the effects of maternal Bifidobacterium bifidum intervention on early-life stress-induced neurobehavioral abnormalities and its mechanisms. Maternal separation model during lactation was established in C57BL/6 mice to mimic early-life stress. Pregnant mice were orally administered Bifidobacterium bifidum, and behavioral performance including open field test, three-chamber social test, and novel object recognition test were measured in offspring to investigate the effects of prenatal probiotic intervention on neurobehavioral outcomes in offspring. Results showed that maternal Bifidobacterium bifidum intervention rescued maternal separation-induced growth retardation and social deficits in offspring. Strain-specific qPCR confirmed maternal-to-offspring transmission of Bifidobacterium bifidum. Probiotic intervention reshaped the offspring gut microbiota, reduced colonic pro-inflammatory factors expression in colon, serum, and hippocampus, decreased the hypothalamic microglial activation marker Iba1 caused by early-life stress, thereby alleviating peripheral immune imbalance and central pro-inflammatory responses. Moreover, maternal Bifidobacterium bifidum intervention upregulated the microbial metabolite 5'-methylthioadenosine, which was significantly related with maternal separation-induced neurobehavioral abnormalities. In vitro, 5'-methylthioadenosine mitigated corticosterone-induced decreased cell viability and inflammatory response in NE-4C cells. Collectively, prenatal Bifidobacterium bifidum intervention alleviates early-life stress-induced offspring neurobehavioral abnormalities by reshaping gut microbiota and suppressing inflammation via microbial metabolite 5'-methylthioadenosine, suggesting the protective effect of gut microbiota metabolite against neurobehavioral abnormalities induced by early-life stress.