Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer's Disease.
Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer's Disease.
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DOI：
10.3390/ijms23010357
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发表时间：
2021-12-29
影响因子：
5.6
通讯作者：
Eleuteri AM
中科院分区：
文献类型：
--
作者：
Bonfili L;Gong C;Lombardi F;Cifone MG;Eleuteri AM
生态失调有助于阿尔茨海默病（AD）的发病机制，并且口服细菌疗法代表了一种有希望的预防和治疗机会，以重塑肠道微生物群并通过减少神经炎症和淀粉样蛋白和tau蛋白聚集来延迟AD的发作和进展。具体而言，SLAB 51多菌株益生菌制剂对多种神经化学途径产生积极影响，但益生菌口服消费和大脑有益作用之间的确切联系仍然是一个知识空白。考虑到AD患者的脑血氧合特别降低，并且神经血管功能降低有助于AD损伤，缺氧调节是治疗中枢神经系统疾病的一种令人鼓舞的策略。在这项工作中，8周龄3xTg-AD和野生型小鼠长期补充SLAB 51，以评估对缺氧诱导因子-1 α（HIF-1α）的影响，HIF-1α是调节宿主-微生物串扰的关键分子，也是神经退行性病变的潜在靶点。我们报告的证据表明，长期补充SLAB 51增强了HIF-1α的脑表达，降低了脯氨酰羟化酶2（PHD 2）的水平，PHD 2是HIF-1α降解的氧依赖性调节剂;此外，它成功地抵消了AD小鼠诱导型一氧化氮合酶（iNOS）脑表达和一氧化氮血浆水平的增加。总之，结果证明了SLAB 51在该AD模型中发挥神经保护和抗炎作用的另外机制。
Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.
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影响因子：
5.1
作者：
Bonfili L;Cecarini V;Cuccioloni M;Angeletti M;Berardi S;Scarpona S;Rossi G;Eleuteri AM
通讯作者：
Eleuteri AM
影响因子：
3.5
作者：
Liu, Ying;Liu, Fei;Gong, Cheng-Xin
通讯作者：
Gong, Cheng-Xin
影响因子：
2.9
作者：
Lüth, HJ;Münch, G;Arendt, T
通讯作者：
Arendt, T
影响因子：
3.2
作者：
Baillieul, S.;Chacaroun, S.;Verges, S.
通讯作者：
Verges, S.
影响因子：
6.1
作者：
Hassan H;Chen R
通讯作者：
Chen R