Garcez Michelle L, Tan Vanessa X, Heng Benjamin, Guillemin Gilles J
Neurochemistry Laboratory, Department of Biochemistry, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
Neurodegenerative diseases Research Group, Faculty of Medicine, Health and Human Sciences, Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
Int J Tryptophan Res. 2020 Dec 28;13:1178646920978404. doi: 10.1177/1178646920978404. eCollection 2020.
The crosstalk between central nervous system (CNS) and gut microbiota plays key roles in neuroinflammation and chronic immune activation that are common features of all neurodegenerative diseases. Imbalance in the microbiota can lead to an increase in the intestinal permeability allowing toxins to diffuse and reach the CNS, as well as impairing the production of neuroprotective metabolites such as sodium butyrate (SB) and indole-3-propionic acid (IPA). The aim of the present study was to evaluate the effect of SB and IPA on LPS-induced production of cytokines and tryptophan metabolites in human astrocytes. Primary cultures of human astrocytes were pre-incubated with SB or IPA for 1 hour before treatment with LPS. Cell viability was not affected at 24, 48 or 72 hours after pre-treatment with SB, IPA or LPS treatment. SB was able to significantly prevent the increase of GM-CSF, MCP-1, IL-6 IL-12, and IL-13 triggered by LPS. SB and IPA also prevented inflammation indicated by the increase in kynurenine and kynurenine/tryptophan ratio induced by LPS treatment. IPA pre-treatment prevented the LPS-induced increase in MCP-1, IL-12, IL-13, and TNF-α levels 24 hours after pre-treatment, but had no effect on tryptophan metabolites. The present study showed for the first time that bacterial metabolites SB and IPA have potential anti-inflammatory effect on primary human astrocytes with potential therapeutic benefit in neurodegenerative disease characterized by the presence of chronic low-grade inflammation.
中枢神经系统（CNS）与肠道微生物群之间的相互作用在神经炎症和慢性免疫激活中起关键作用，而这是所有神经退行性疾病的共同特征。微生物群的失衡会导致肠道通透性增加，使毒素扩散并到达中枢神经系统，同时还会损害神经保护代谢产物如丁酸钠（SB）和吲哚 - 3 - 丙酸（IPA）的产生。本研究的目的是评估SB和IPA对脂多糖（LPS）诱导的人星形胶质细胞中细胞因子和色氨酸代谢产物产生的影响。在用人星形胶质细胞进行原代培养时，先用SB或IPA预孵育1小时，然后再用LPS处理。在用SB、IPA或LPS预处理后的24、48或72小时，细胞活力未受影响。SB能够显著抑制由LPS触发的GM - CSF、MCP - 1、IL - 6、IL - 12和IL - 13的增加。SB和IPA还能抑制LPS处理诱导的犬尿氨酸和犬尿氨酸/色氨酸比值增加所表明的炎症。IPA预处理可在预处理后24小时抑制LPS诱导的MCP - 1、IL - 12、IL - 13和TNF - α水平升高，但对色氨酸代谢产物没有影响。本研究首次表明，细菌代谢产物SB和IPA对原代人星形胶质细胞具有潜在的抗炎作用，在以慢性低度炎症为特征的神经退行性疾病中具有潜在的治疗益处。
