Department of Molecular and Cellular Pathology of Alcohol, Príncipe Felipe Research Center, 46012 Valencia, Spain.
Department of Physiology, School of Medicine and Dentistry, University of Valencia, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain.
Int J Mol Sci. 2021 Apr 19;22(8):4235. doi: 10.3390/ijms22084235.
Human intestinal microbiota comprise of a dynamic population of bacterial species and other microorganisms with the capacity to interact with the rest of the organism and strongly influence the host during homeostasis and disease. Commensal and pathogenic bacteria coexist in homeostasis with the intestinal epithelium and the gastrointestinal tract's immune system, or GALT (gut-associated lymphoid tissue), of the host. However, a disruption to this homeostasis or dysbiosis by different factors (e.g., stress, diet, use of antibiotics, age, inflammatory processes) can cause brain dysfunction given the communication between the gut and brain. Recently, extracellular vesicles (EVs) derived from bacteria have emerged as possible carriers in gut-brain communication through the interaction of their vesicle components with immune receptors, which lead to neuroinflammatory immune response activation. This review discusses the critical role of bacterial EVs from the gut in the neuropathology of brain dysfunctions by modulating the immune response. These vesicles, which contain harmful bacterial EV contents such as lipopolysaccharide (LPS), peptidoglycans, toxins and nucleic acids, are capable of crossing tissue barriers including the blood-brain barrier and interacting with the immune receptors of glial cells (e.g., Toll-like receptors) to lead to the production of cytokines and inflammatory mediators, which can cause brain impairment and behavioral dysfunctions.
人类肠道微生物群由具有与机体其他部分相互作用的能力的细菌物种和其他微生物组成,并在稳态和疾病期间强烈影响宿主。共生菌和病原菌与肠道上皮和宿主的胃肠道免疫系统(即肠道相关淋巴组织,GALT)在稳态中共存。然而,由于肠道和大脑之间的通讯,不同因素(例如压力、饮食、使用抗生素、年龄、炎症过程)的这种稳态破坏或失调会导致大脑功能障碍。最近,源自细菌的细胞外囊泡(EVs)已成为通过其囊泡成分与免疫受体相互作用进行肠道-大脑通讯的可能载体,这导致神经炎症免疫反应的激活。本文综述了肠道细菌 EVs 通过调节免疫反应在大脑功能障碍的神经病理学中的关键作用。这些囊泡含有脂多糖(LPS)、肽聚糖、毒素和核酸等有害的细菌 EV 内容物,能够穿过包括血脑屏障在内的组织屏障,并与神经胶质细胞的免疫受体(如 Toll 样受体)相互作用,导致细胞因子和炎症介质的产生,从而导致脑损伤和行为功能障碍。
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