Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity.
Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity.
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DOI：
10.3389/fimmu.2021.670500
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发表时间：
2021
影响因子：
7.3
通讯作者：
Pasinetti GM
中科院分区：
文献类型：
--
作者：
Westfall S;Caracci F;Estill M;Frolinger T;Shen L;Pasinetti GM
慢性应激表现为抑郁和焦虑样行为，而经常性应激则导致与应激诱导的免疫启动相关的不成比例的行为障碍。肠-脑-微生物群轴是应激诱导的行为障碍的有希望的治疗靶点，因为它同时调节外周和脑免疫学景观。在这项研究中，益生菌和益生元的组合（称为合生元）通过使肠道微生物群正常化并通过调节回肠先天淋巴细胞（ILC）3活性促进调节性T细胞（Treg）扩增，促进对慢性和复发性应激的行为恢复力，这种影响反映了比边缘脑区神经炎症更好的行为反应。支持这一结论的是，多变量机器学习模型相关地预测了应激诱导的行为障碍的跨组织免疫特征，其中回肠Treg/T辅助细胞17细胞比率与应激诱导的行为缺陷背景下的海马趋化性趋化因子和前额叶皮质IL-1β产生相关。总之，应激诱导的行为障碍依赖于肠-脑-微生物群轴，合生元通过回肠免疫调节减轻相关的抑郁和焦虑样行为。
Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate behavioral impairments linked to stress-induced immunological priming. The gut-brain-microbiota-axis is a promising therapeutic target for stress-induced behavioral impairments as it simultaneously modulates peripheral and brain immunological landscapes. In this study, a combination of probiotics and prebiotics, known as a synbiotic, promoted behavioral resilience to chronic and recurrent stress by normalizing gut microbiota populations and promoting regulatory T cell (Treg) expansion through modulation of ileal innate lymphoid cell (ILC)3 activity, an impact reflecting behavioral responses better than limbic brain region neuroinflammation. Supporting this conclusion, a multivariate machine learning model correlatively predicted a cross-tissue immunological signature of stress-induced behavioral impairment where the ileal Treg/T helper17 cell ratio associated to hippocampal chemotactic chemokine and prefrontal cortex IL-1β production in the context of stress-induced behavioral deficits. In conclusion, stress-induced behavioral impairments depend on the gut-brain-microbiota-axis and through ileal immune regulation, synbiotics attenuate the associated depressive- and anxiety-like behavior.
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DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Christensen, HR;Frokiær, H;Pestka, JJ
通讯作者：
Pestka, JJ
影响因子：
4.6
作者：
Frolinger, Tal;Sims, Steven;Pasinetti, Giulio M.
通讯作者：
Pasinetti, Giulio M.
影响因子：
2.9
作者：
Grippo, AJ;Francis, J;Johnson, AK
通讯作者：
Johnson, AK
影响因子：
10.6
作者：
Franklin TC;Wohleb ES;Zhang Y;Fogaça M;Hare B;Duman RS
通讯作者：
Duman RS