2024-11-22 カリフォルニア大学リバーサイド校(UCR)
◆マウスを用いた実験で、妊娠中および授乳期の母親にPBDEを曝露し、一部にはLRを補給しました。その結果、PBDEに曝露された雄の子孫で体重増加の遅れや歯の萌出の異常が観察されましたが、LRの補給によりこれらの影響が軽減されました。また、雌の子孫では過度の掘削行動や多動性が見られましたが、LRの補給でこれらの行動も改善されました。さらに、LRはグルコース代謝やインスリンレベルの改善にも寄与しました。この研究は、母体へのプロバイオティクス補給が、PBDEによる神経発達や代謝への悪影響を予防する可能性を示唆しています。
<関連情報>
- https://news.ucr.edu/articles/2024/11/22/probiotic-may-counteract-fire-retardant-chemical-damage
- https://link.springer.com/article/10.1007/s00204-024-03882-4
プロバイオティクスの母体への補充は、PBDEによる発育、行動、代謝のリプログラミングを性差なく予防する: 腸内細菌叢の役割 Maternal probiotic supplementation protects against PBDE-induced developmental, behavior and metabolic reprogramming in a sexually dimorphic manner: Role of gut microbiome
Maximillian E. Denys,Elena V. Kozlova,Rui Liu,Anthony E. Bishay,Elyza A. Do,Varadh Piamthai,Yash V. Korde,Crystal N. Luna,Artha A. Lam,Ansel Hsiao & Margarita Currás-Collazo
Archives of Toxicology Published:09 November 2024
DOI:https://doi.org/10.1007/s00204-024-03882-4
Abstract
Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting persistent organic pollutants (POPs) used as flame retardants in a wide range of commercial applications. We have previously reported neurobehavioral and metabolic reprogramming produced by developmental PBDEs. PBDEs perturb the microbiome, an influencer of life-long health, while probiotic supplementation with Limosilactobacillus reuteri (LR) can avert neurobehavioral and endocrine disruption. We, therefore, tested the hypothesis that perinatal maternal LR supplementation would protect gut microbiome richness and diversity, developmental milestones, adult neurobehavior and metabolic homeostasis in PBDE-exposed offspring. C57BL/6N dams were orally exposed to a commercial penta-mixture of PBDEs, DE-71, at 0.1 mg/kg/day, or corn oil vehicle (VEH/CON) during gestation and lactation. Mice offspring received DE-71 or VEH/CON with or without co-administration of LR (ATCC-PTA-6475) indirectly via their mother from gestational day (GD) 0 until postnatal day (P)21 (Cohort 1), or continued to receive LR directly from P22 through adulthood (Cohort 2). Results of fecal 16S rRNA sequencing indicated age- and sex-dependent effects of DE-71 on gut microbial communities. Maternal LR treatment protected against DE-71-induced reduction in α-diversity in P22 females and against β-diversity alterations in P30 males. In females, DE-71 changed the relative abundance of specific bacterial taxa, such as Tenericutes and Cyanobacteria (elevated) and Deferribacterota (reduced). In males, several Firmicutes taxa were elevated, while Proteobacteria, Chlamydiae, and several Bacteroidota taxa were reduced. The number of disrupted taxa normalized by maternal LR supplementation was as follows: 100% in P22 females and 33% in males at P22 and 25% at P30. Maternal LR treatment protected against DE-71-induced delay of postnatal body weight gain in males and ameliorated the abnormal timing of incisor eruption in both sexes. Further, DE-71 produced exaggerated digging in both sexes as well as locomotor hyperactivity in females, effects that were mitigated by maternal LR only in females. Other benefits of LR therapy included normalization of glucose tolerance, insulin-to-glucose ratio and plasma leptin in adult DE-71 females (Cohort 2). This study provides evidence that probiotic supplementation can mitigate POP-induced reprogramming of neurodevelopment, adult neurobehavior, and glucose metabolism in association with modified gut microbial community structure in a sex-dependent manner.
Highlights
- Maternal Limosilactobacillus reuteri (LR) supplementation sex-dependently normalized DE-71-induced gut dysbiosis in offspring.
- Maternal DE-71 sex-dependently altered the timing of offspring postnatal developmental benchmarks.
- Maternal LR ameliorated DE-71-induced delay in male body weight gain.
- Maternal LR normalized sex-dependent DE-71-induced reprogramming of adult glucose homeostasis.
- Maternal LR prevented DE-71-induced hyperactivity and repetitive behavior in adult female offspring.
