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给应激大鼠使用益生菌罗伊氏乳杆菌进行治疗,可改善母性行为,并纠正皮质酮-脑源性神经营养因子-催产素平衡,为产后产妇应激障碍的治疗提供了思路。

Probiotic L. reuteri treatment in stressed rats improves maternal care and corrects corticosterone-BDNF-oxytocin balance offering insights for maternal postpartum distress treatment.

作者信息

Benlakehal Ryma, Gaetano Alessandra, Charlet Rogatien, Bouwalerh Hammou, Cogez Virginie, Harduin-Lepers Anne, Sendid Boualem, Nicoletti Ferdinando, Maccari Stefania, Morley-Fletcher Sara

机构信息

CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, GlycoStress team, LIA-CNRS, Université de Lille, 59655, Villeneuve d'Ascq, France.

CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, INSERM U1285, Glycobiology in Fungal Pathogenesis & Clinical application team, CHU, Université de Lille, 59000, Lille, France.

出版信息

Sci Rep. 2025 Jul 2;15(1):23544. doi: 10.1038/s41598-025-05848-7.

DOI:10.1038/s41598-025-05848-7
PMID:40604032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12222657/
Abstract

Mothers experiencing depressive symptoms or gestational stress are at risk of developing maternal distress, which, in its most severe form, can progress to postpartum depression, profoundly affecting maternal well-being and infant care. Using a late-gestation restraint stress model, we investigated whether postpartum treatment of lactating dams with probiotic Limosilactobacillus reuteri (L. reuteri) could reverse stress-induced disruptions in maternal behavior and neurobiology. L. reuteri effectively improved maternal care, and restored reactivity to pup separation in stressed dams. Postpartum L. reuteri also corrected corticosterone-oxytocin imbalances in plasma, normalized hypothalamic oxytocin levels, the unglycosylated and glycosylated oxytocin receptor isoforms and it regulated the ratio of precursor to mature brain-derived neurotrophic factor (BDNF). Additionally, L. reuteri restored gut microbiota balance, increasing Lactobacillus spp. while reducing pathogenic strains in fecal pellets of stressed dams during lactation and post-weaning, correlating with both maternal oxytocin and corticosterone plasma levels. This study is the first to demonstrate the therapeutic efficacy of a probiotic and its molecular support in counteracting the adverse effects of gestational stress on maternal care through brain-gut axis mechanisms. These findings support probiotic-based interventions as safe, complementary preventive strategy for improving maternal health in conditions involving impaired maternal care and microbiota dysbiosis.

摘要

经历抑郁症状或孕期压力的母亲有患母体应激的风险,最严重时可发展为产后抑郁,这会深刻影响母亲的幸福感和婴儿护理。我们采用妊娠晚期束缚应激模型,研究了产后给哺乳期母鼠使用益生菌罗伊氏乳杆菌(L. reuteri)是否能逆转应激引起的母性行为和神经生物学紊乱。罗伊氏乳杆菌有效改善了母性护理,并恢复了应激母鼠对幼崽分离的反应性。产后使用罗伊氏乳杆菌还纠正了血浆中皮质酮 - 催产素的失衡,使下丘脑催产素水平、未糖基化和糖基化的催产素受体亚型正常化,并调节了前体脑源性神经营养因子(BDNF)与成熟BDNF的比例。此外,罗伊氏乳杆菌恢复了肠道微生物群平衡,增加了哺乳期和断奶后应激母鼠粪便颗粒中的乳酸杆菌属,同时减少了致病菌株,这与母体催产素和皮质酮血浆水平相关。本研究首次证明了益生菌及其分子支持通过脑 - 肠轴机制对抗孕期应激对母性护理的不利影响的治疗效果。这些发现支持基于益生菌的干预措施作为一种安全的补充预防策略,用于改善涉及母性护理受损和微生物群失调情况的孕产妇健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1cd/12222657/fb435b833a5b/41598_2025_5848_Fig6_HTML.jpg
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本文引用的文献

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肠道微生物失调通过产后抑郁小鼠模型中海马 NLRP3 介导的神经炎症导致抑郁样行为。
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Neonatal oxytocin treatment alters levels of precursor and mature BDNF forms and modifies the expression of neuronal markers in the male rat hippocampus.新生鼠催产素处理改变了脑源性神经营养因子前体和成熟形式的水平,并修饰了雄性大鼠海马神经元标记物的表达。
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