Department of Occupational and Environmental Health, Guilin Medical University, Guilin, China; Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, China.
Department of Psychiatry, Wuhan Wudong Hospital, Wuhan, China.
Ecotoxicol Environ Saf. 2023 Jul 1;259:115041. doi: 10.1016/j.ecoenv.2023.115041. Epub 2023 May 23.
2,2',4,4'-tetrabromodiphenyl ether (BDE47) is a foodborne environmental risk factor for depression, but the pathogenic mechanism has yet to be fully characterized. In this study, we clarified the effect of BDE47 on depression in mice. The abnormal regulation of the microbiome-gut-brain axis is evidenced closely associated with the development of depression. Using RNA sequencing, metabolomics, and 16s rDNA amplicon sequencing, the role of the microbiome-gut-brain axis in depression was also explored. The results showed that BDE47 exposure increased depression-like behaviors in mice but inhibited the learning memory ability of mice. The RNA sequencing analysis showed that BDE47 exposure disrupted dopamine transmission in the brain of mice. Meanwhile, BDE47 exposure reduced protein levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT), activated astrocytes and microglia cells, and increased protein levels of NLRP3, IL-6, IL-1β, and TNF-α in the brain of mice. The 16 s rDNA sequencing analysis showed that BDE47 exposure disrupted microbiota communities in the intestinal contents of mice, and faecalibaculum was the most increased genus. Moreover, BDE47 exposure increased the levels of IL-6, IL-1β, and TNF-α in the colon and serum of mice but decreased the levels of tight junction protein ZO-1 and Occludin in the colon and brain of mice. In addition, the metabolomic analysis revealed that BDE47 exposure induced metabolic disorders of arachidonic acid and neurotransmitter 2-Arachidonoyl glycerol (2-AG) was one of the most decreased metabolites. Correlation analysis further revealed gut microbial dysbiosis, particularly faecalibaculum, is associated with altered gut metabolites and serum cytokines in response to BDE47 exposure. Our results suggest that BDE47 might induce depression-like behavior in mice through gut microbial dysbiosis. The mechanism might be associated with the inhibited 2-AG signaling and increased inflammatory signaling in the gut-brain axis.
2,2',4,4'-四溴二苯醚 (BDE47) 是一种食源性环境风险因素，可导致抑郁，但发病机制尚未完全阐明。在本研究中，我们阐明了 BDE47 对小鼠抑郁的影响。微生物组-肠道-大脑轴的异常调节与抑郁的发展密切相关。使用 RNA 测序、代谢组学和 16s rDNA 扩增子测序，还探讨了微生物组-肠道-大脑轴在抑郁中的作用。结果表明，BDE47 暴露增加了小鼠的抑郁样行为，但抑制了小鼠的学习记忆能力。RNA 测序分析表明，BDE47 暴露破坏了小鼠大脑中的多巴胺传递。同时，BDE47 暴露降低了小鼠大脑中酪氨酸羟化酶 (TH) 和多巴胺转运蛋白 (DAT) 的蛋白水平，激活了星形胶质细胞和小胶质细胞，并增加了 NLRP3、IL-6、IL-1β 和 TNF-α 的蛋白水平。16s rDNA 测序分析表明，BDE47 暴露破坏了小鼠肠道内容物中的微生物群落，而 Faecalibaculum 是最增加的属。此外，BDE47 暴露增加了小鼠结肠和血清中 IL-6、IL-1β 和 TNF-α 的水平，但降低了结肠和大脑中紧密连接蛋白 ZO-1 和 Occludin 的水平。此外，代谢组学分析表明，BDE47 暴露诱导花生四烯酸代谢紊乱，神经递质 2-花生四烯酰甘油 (2-AG) 是最减少的代谢物之一。相关性分析进一步表明，BDE47 暴露引起的肠道微生物失调，特别是 Faecalibaculum，与肠道代谢物和血清细胞因子的改变有关。我们的结果表明，BDE47 可能通过肠道微生物失调诱导小鼠出现抑郁样行为。其机制可能与肠道-大脑轴中 2-AG 信号的抑制和炎症信号的增加有关。
