Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors.
Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors.
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DOI：
10.1016/j.bbi.2020.10.013
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Pasinetti GM
中科院分区：
文献类型：
--
作者：
Westfall S;Caracci F;Zhao D;Wu QL;Frolinger T;Simon J;Pasinetti GM
慢性应激会破坏免疫稳态，而肠道微生物衍生的代谢产物会减轻炎症，从而促进对应激诱导的免疫和行为异常的恢复力。外周和大脑区域特异性的免疫反应对慢性应激的适应不良，产生了设计预防应激诱导的心理障碍的新治疗策略所需的相关机制考虑。这项研究表明，益生菌和富含多酚的益生元（一种合生元）的组合可以减弱回肠和前额皮质中慢性应激诱导的炎症反应，从而促进雄性小鼠对随后的抑郁和焦虑样行为的恢复。药代动力学研究表明，这种作用可能归因于特定的合生元产生的代谢产物，包括4-羟基苯基丙酸，4-羟基苯乙酸和咖啡酸。使用慢性不可预测的压力模型，行为异常与回肠中强烈的免疫细胞激活和募集有关，而炎症体通路与前额皮质和海马有关。慢性应激还上调了肝脏和回肠中激活的促炎性辅助性T细胞17（Th 17）与调节性T细胞（Treg）的比例，并且通过独创性途径分析预测，芳烃受体（AHR）可能会驱动合生素对回肠的影响应激炎症反应。合生素治疗不加区别地减弱了回肠和大脑中的应激诱导的免疫和行为畸变，而在肠道免疫共培养模型中，合生素特异性代谢物通过AHR促进抗炎活性。总的来说，这项研究表征了一种新型合生素治疗慢性应激诱导的行为障碍，同时定义了肠道微生物群宿主相互作用的假定机制，用于调节外周和大脑免疫系统。
Chronic stress disrupts immune homeostasis while gut microbiota-derived metabolites attenuate inflammation, thus promoting resilience to stress-induced immune and behavioral abnormalities. There are both peripheral and brain region-specific maladaptations of the immune response to chronic stress that produce interrelated mechanistic considerations required for the design of novel therapeutic strategies for prevention of stress-induced psychological impairment. This study shows that a combination of probiotics and polyphenol-rich prebiotics, a synbiotic, attenuates the chronic-stress induced inflammatory responses in the ileum and the prefrontal cortex promoting resilience to the consequent depressive- and anxiety-like behaviors in male mice. Pharmacokinetic studies revealed that this effect may be attributed to specific synbiotic-produced metabolites including 4-hydroxyphenylpropionic, 4-hydroxyphenylacetic acid and caffeic acid. Using a model of chronic unpredictable stress, behavioral abnormalities were associated to strong immune cell activation and recruitment in the ileum while inflammasome pathways were implicated in the prefrontal cortex and hippocampus. Chronic stress also upregulated the ratio of activated proinflammatory T helper 17 (Th17) to regulatory T cells (Treg) in the liver and ileum and it was predicted with ingenuity pathway analysis that the aryl hydrocarbon receptor (AHR) could be driving the synbiotic’s effect on the ileum’s inflammatory response to stress. Synbiotic treatment indiscriminately attenuated the stress-induced immune and behavioral aberrations in both the ileum and the brain while in a gut-immune co-culture model, the synbiotic-specific metabolites promoted anti-inflammatory activity through the AHR. Overall, this study characterizes a novel synbiotic treatment for chronic-stress induced behavioral impairments while defining a putative mechanism of gut-microbiota host interaction for modulating the peripheral and brain immune systems.
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DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.
影响因子：
64.5
作者：
Bellono NW;Bayrer JR;Leitch DB;Castro J;Zhang C;O'Donnell TA;Brierley SM;Ingraham HA;Julius D
通讯作者：
Julius D
影响因子：
32.4
作者：
Britton, Graham J.;Contijoch, Eduardo J.;Faith, Jeremiah J.
通讯作者：
Faith, Jeremiah J.
小檗碱通过调节结肠肠道微生物群调节 Treg/Th17 平衡来治疗溃疡性结肠炎
影响因子：
5.6
作者：
Cui H;Cai Y;Wang L;Jia B;Li J;Zhao S;Chu X;Lin J;Zhang X;Bian Y;Zhuang P
通讯作者：
Zhuang P