Probiotic treatment rescues behavioral deficits and gut microbial abnormalities induced by preconceptional stress in mothers and offspring

Mar 31, 2026Brain, behavior, and immunity

Probiotics improve behavior and gut bacteria problems caused by stress before pregnancy in mothers and their children

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Abstract

Preconceptional social isolation rearing (SIR) in female mice is associated with increased anxiety-like behavior and reduced gut microbial diversity.

SIR females exhibited reduced diversity in gut microbiota and specific alterations in bacterial populations.
Behavioral changes included heightened anxiety-like and social-avoidant behaviors in SIR females.
Maternal probiotic supplementation reversed behavioral changes and restored microbial diversity in SIR females.
Offspring of SIR dams displayed sex-dependent behavioral deficits and microbial alterations that reflected maternal conditions.
Prenatal SIR was linked to reduced expression of a brain-derived neurotrophic factor (Bdnf) in offspring.
Probiotic treatment during pregnancy resulted in broader transcriptional effects and normalization of Bdnf levels in SIR offspring.

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Depression and anxiety during pregnancy are major public health concerns with lasting consequences for mother and child. Although the gut microbiome contributes to stress and mood regulation, its role in preconceptional stress and transgenerational outcomes remains unclear. Here, we examined behavioral, microbial, and thalamic transcriptional effects of preconceptional social isolation rearing (SIR) in female mice and tested whether maternal probiotic supplementation mitigates these alterations. SIR females displayed increased anxiety-like and social-avoidant behavior, reduced gut microbial diversity, depletion of Odoribacter, Tuzzerella, and Alloprevotella, and enrichment of Bacteroides and Lachnospiraceae. A multispecies probiotic (Lactobacillus rhamnosus HN001, L. acidophilus La-14, Bifidobacterium lactis HN019) reversed these behavioral and microbial changes. Adult offspring of SIR dams showed sex-dependent behavioral deficits and microbial alterations partly reflecting maternal patterns. Prenatal SIR was associated with reduced thalamic Bdnf expression in offspring and altered Grin2a/2b selectively in males. In contrast, prenatal probiotic exposure exerted broader transcriptional effects and restored Bdnf levels in SIR offspring. SIR-induced increases in Lachnospiraceae were transmitted to offspring, whereas reductions in Ruminococcaceae were normalized by maternal probiotic treatment. Predicted functional profiling indicated sex-dependent modulation of microbial pathways related to tryptophan and central carbon metabolism. These findings demonstrate enduring transgenerational effects of preconceptional stress on the gut-brain axis and support maternal probiotic supplementation as a potential strategy to mitigate stress-induced dysregulation.

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Probiotic treatment rescues behavioral deficits and gut microbial abnormalities induced by preconceptional stress in mothers and offspring

Abstract

Full Text

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