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

Depression and anxiety during pregnancy pose significant public health challenges, adversely affecting both maternal and child health. This research explores the influence of the gut microbiome on stress and mood regulation, particularly concerning preconceptional stress and its transgenerational effects.

Using a model of preconceptional social isolation rearing (SIR) in female mice, we observed increased anxiety-like behaviors, diminished gut microbial diversity, and specific microbial alterations—including a depletion of Odoribacter, Tuzzerella, and Alloprevotella, alongside an enrichment of Bacteroides and Lachnospiraceae. Notably, administration of a multispecies probiotic (comprising Lactobacillus rhamnosus HN001, L. acidophilus La-14, and Bifidobacterium lactis HN019) successfully reversed these behavioral and microbial changes.

Offspring of SIR dams exhibited sex-dependent behavioral deficits and microbial alterations that partly mirrored maternal patterns. Furthermore, prenatal SIR correlated with reduced expression of Bdnf in the thalamus of offspring, with alterations in Grin2a/2b observed selectively in males. Conversely, prenatal exposure to probiotics not only exerted broader transcriptional effects but also restored Bdnf levels in SIR offspring. While SIR-induced increases in Lachnospiraceae were transmitted to offspring, reductions in Ruminococcaceae were normalized through maternal probiotic treatment. Functional profiling indicated a sex-dependent modulation of microbial pathways associated with tryptophan and central carbon metabolism.

In conclusion, these findings underscore the lasting transgenerational effects of preconceptional stress on the gut-brain axis and advocate for maternal probiotic supplementation as a viable strategy to alleviate stress-induced dysregulation. [NPID: preconception stress, pregnancy, microbiome, probiotic, anxiety]

Year: 2026

Reference: Iachizzi, M., Zajac, N., Ruiz, J. L., Güller, T., Rabin, R., Schalbetter, S., De Cillis, F., Moccia, M. D., Cattaneo, A., Cryan, J. F., & Richetto, J. (2026). Probiotic treatment rescues behavioral deficits and gut microbial abnormalities induced by preconceptional stress in mothers and offspring. Brain, Behavior, and Immunity, 136, 106571. https://doi.org/10.1016/j.bbi.2026.106571