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益生菌SLAB51作为对抗双酚A对斑马鱼肠道微生物群-肝脏-脑轴毒性的制剂。

The probiotic SLAB51 as agent to counteract BPA toxicity on zebrafish gut microbiota -liver-brain axis.

作者信息

Giommi Christian, Lombó Marta, Habibi Hamid R, Rossi Giacomo, Basili Danilo, Mangiaterra Sara, Ladisa Claudia, Chemello Giulia, Carnevali Oliana, Maradonna Francesca

机构信息

Dipartimento Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy; INBB - Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy.

Dipartimento Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy; INBB - Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy; Department of Molecular Biology, Faculty of Biology and Environmental Sciences, Universidad de León, 24071 León, Spain.

出版信息

Sci Total Environ. 2024 Feb 20;912:169303. doi: 10.1016/j.scitotenv.2023.169303. Epub 2023 Dec 20.

DOI:10.1016/j.scitotenv.2023.169303
PMID:38135076
Abstract

A plethora of studies have so far described the toxic effects of bisphenol A (BPA) on organism health, highlighting the urgent need to find new strategies not only to reduce the presence of this toxicant but also to counteract its adverse effects. In this context, probiotics emerged as a potential tool since they promote organism welfare. Using a multidisciplinary approach, this study explores the effects of SLAB51 dietary administration to counteract BPA toxicity using zebrafish as a model. Adult males and females were maintained under standard conditions (control group; C), exposed for 28 days via the water to an environmental relevant dose of BPA (10 μg/L; BPA), dietary treated with SLAB51 (10 CFU/g of body weight; P) and co-treated with BPA plus SLAB51 (BPA + P). In the gut, exposure to BPA resulted in altered architecture in both males and females, with females also experiencing an increase of pathogenic bacterial species. Co-administration of BPA + P led to the restoration of normal gut architecture, favored beneficial bacteria colonization, and decreased the abundance of pathogenic species. In the liver, male BPA exposure led to steatosis and glycogen depletion, which was partially mitigated by SLAB51 co-administration. In contrast, in females exposed to BPA, the lack of steatosis along with the greater glycogen depletion, suggested an increase in energy demand as supported by the metabolomic phenotype. The analysis of liver metabolites in BPA + P males revealed increased levels of anserine and reduced levels of glutamine, which could lie behind the counteraction of the brain histopathological damage caused by BPA. In BPA + P females, a reduction of retinoic acid was found in the liver, suggesting an increase in retinoids responsible for BPA detoxification. Overall, these results demonstrate that SLAB51 exerts its beneficial effects on the gut microbiota-brain-liver axis through distinct molecular pathways, effectively mitigating the pleiotropic toxicity of BPA.

摘要

迄今为止,大量研究描述了双酚A(BPA)对生物体健康的毒性作用,凸显了迫切需要找到新策略,不仅要减少这种有毒物质的存在,还要抵消其不良影响。在这种背景下,益生菌作为一种潜在工具应运而生,因为它们能促进生物体健康。本研究采用多学科方法,以斑马鱼为模型,探索给予SLAB51饮食对抵消BPA毒性的影响。成年雄性和雌性斑马鱼饲养在标准条件下(对照组;C),通过水暴露于环境相关剂量的BPA(10μg/L;BPA组),给予SLAB51饮食处理(10CFU/g体重;P组),以及BPA与SLAB51联合处理(BPA + P组)。在肠道中,暴露于BPA导致雄性和雌性斑马鱼的肠道结构改变,雌性斑马鱼还出现致病细菌种类增加。BPA与SLAB51联合给药导致肠道结构恢复正常,有利于有益菌定殖,并减少了致病菌种的丰度。在肝脏中,雄性斑马鱼暴露于BPA导致脂肪变性和糖原耗竭,而SLAB51联合给药可部分缓解这种情况。相比之下,在暴露于BPA的雌性斑马鱼中,没有脂肪变性但糖原耗竭更严重,这表明代谢组学表型支持能量需求增加。对BPA + P组雄性斑马鱼肝脏代谢物的分析显示,鹅肌肽水平升高,谷氨酰胺水平降低,这可能是抵消BPA引起的脑组织病理损伤的原因。在BPA + P组雌性斑马鱼中,肝脏中视黄酸减少,表明负责BPA解毒的类视黄醇增加。总体而言,这些结果表明,SLAB51通过不同的分子途径对肠道微生物群-脑-肝轴发挥有益作用,有效减轻了BPA的多效性毒性。

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