Treatment with Bacterial Biologics Promotes Healthy Aging and Traumatic Brain Injury Responses in Adult Drosophila, Modeling the Gut-Brain Axis and Inflammation Responses.
Treatment with Bacterial Biologics Promotes Healthy Aging and Traumatic Brain Injury Responses in Adult Drosophila, Modeling the Gut-Brain Axis and Inflammation Responses.
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DOI：
10.3390/cells10040900
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发表时间：
2021-04-14
期刊：
影响因子：
6
通讯作者：
Finley K
中科院分区：
文献类型：
--
作者：
Molina B;Mastroianni J;Suarez E;Soni B;Forsberg E;Finley K
果蝇被广泛用于研究神经发育、免疫和与肠-脑轴相关的炎症途径和过程。在这里，我们研究了给予无活性细菌（IAB;保加利亚乳杆菌的专有裂解物制剂，ReseT®）和益生菌（鼠李糖乳杆菌，LGG）的成年果蝇的反应。在体外实验中，IAB激活了人类细胞中保守的Toll样受体（TLR）和核苷酸结合，寡聚化结构域蛋白（NOD）受体的一个子集，口服给药减缓了成年果蝇运动行为的年龄相关性下降。平均而言，IAB处理的果蝇寿命显著延长（+23%），神经聚集体分布较低。不同IAB剂量也改善了创伤性脑损伤（TBI）暴露后的运动功能和寿命概况。从机制上讲，短期IA B和LGG治疗改变了神经和腹部组织中活化B细胞（NF-κβ）的基线核因子κ轻链增强子信号传导谱。总体而言，在选定剂量下，IAB和LGG暴露对果蝇寿命、神经衰老和轻度创伤性脑损伤（TBI）相关反应具有积极影响，其中IAB显示出更大的益处。这包括严重TBI（sTBI）反应，其中IAB治疗具有保护作用，LGG增加了急性死亡率。这项工作表明，果蝇是测试基于细菌的生物制剂的有效模型，IAB和益生菌治疗促进神经元健康并影响神经和免疫组织中的炎症通路。因此，靶向IAB治疗是促进肠-脑轴适当功能的新策略。
Drosophila are widely used to study neural development, immunity, and inflammatory pathways and processes associated with the gut–brain axis. Here, we examine the response of adult Drosophila given an inactive bacteriologic (IAB; proprietary lysate preparation of Lactobacillus bulgaricus, ReseT®) and a probiotic (Lactobacillus rhamnosus, LGG). In vitro, the IAB activates a subset of conserved Toll-like receptor (TLR) and nucleotide-binding, oligomerization domain-containing protein (NOD) receptors in human cells, and oral administration slowed the age-related decline of adult Drosophila locomotor behaviors. On average, IAB-treated flies lived significantly longer (+23%) and had lower neural aggregate profiles. Different IAB dosages also improved locomotor function and longevity profiles after traumatic brain injury (TBI) exposure. Mechanistically, short-term IAB and LGG treatment altered baseline nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling profiles in neural and abdominal tissues. Overall, at select dosages, IAB and LGG exposure has a positive impact on Drosophila longevity, neural aging, and mild traumatic brain injury (TBI)-related responses, with IAB showing greater benefit. This includes severe TBI (sTBI) responses, where IAB treatment was protective and LGG increased acute mortality profiles. This work shows that Drosophila are an effective model for testing bacterial-based biologics, that IAB and probiotic treatments promote neuronal health and influence inflammatory pathways in neural and immune tissues. Therefore, targeted IAB treatments are a novel strategy to promote the appropriate function of the gut–brain axis.
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影响因子：
4.7
作者：
Breit S;Kupferberg A;Rogler G;Hasler G
通讯作者：
Hasler G
DOI：
10.1007/s13311-017-0600-5
发表时间：
2018-01
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Farzi A;Fröhlich EE;Holzer P
通讯作者：
Holzer P
影响因子：
4.6
作者：
Barekat A;Gonzalez A;Mauntz RE;Kotzebue RW;Molina B;El-Mecharrafie N;Conner CJ;Garza S;Melkani GC;Joiner WJ;Lipinski MM;Finley KD;Ratliff EP
通讯作者：
Ratliff EP
影响因子：
13.3
作者：
Bartlett, Bryan J.;Isakson, Pauline;Finley, Kim D.
通讯作者：
Finley, Kim D.
影响因子：
2.5
作者：
Elder, Gregory A.;Ehrlich, Michelle E.;Gandy, Sam
通讯作者：
Gandy, Sam