菌群代谢物或提高小鼠对应激性焦虑和抑郁的恢复力
  • 益生菌和富含多酚的合生元联用,减弱回肠和前额叶皮层的慢行应激炎症反应,提高雄性小鼠从抑郁和焦虑样行为中恢复的能力;
  • 这种功效或与合生元代谢物——4-羟基苯丙酸、4-羟基苯乙酸和咖啡酸有关;
  • 小鼠的行为异常与回肠内免疫细胞的强激活和招募有关,同时激活前额叶皮层和海马的炎症小体通路,还上调肝、回肠中Th17与Treg的比值;
  • 联合治疗改善回肠和大脑中应激性免疫和行为异常,其代谢产物通过芳基烃受体促进抗炎活性。
主编推荐语
爱的抉择
慢行应激会破坏免疫稳态,而肠道微生物代谢产物则会减弱炎症,从而提高机体对应激诱导的免疫和行为异常的恢复能力。Brain Behavior and Immunity近期发表的文章,发现益生菌和富含多酚的后生元联用可减轻机体回肠和大脑中应激性免疫和行为异常,描述了一种新的联合生物治疗慢性应激性行为损伤的方法,同时定义了肠道微生物-宿主相互作用调节周围和脑免疫系统的潜在机制。
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Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors

菌群代谢物调节Th17/Treg失衡,促进对应激性焦虑和抑郁样行为的恢复

10.1016/j.bbi.2020.10.013

2020-10-21, Article

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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.

First Authors:
Susan Westfall

Correspondence Authors:
Giulio Maria Pasinetti

All Authors:
Susan Westfall,Francesca Caracci,Danyue Zhao,Qing-li Wu,Tal Frolinger,James Simon,Giulio Maria Pasinetti

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