Li Zhiming, Lai Jianbo, Zhang Peifen, Ding Jiahong, Jiang Jiajun, Liu Chuanfa, Huang Huimin, Zhen Hefu, Xi Caixi, Sun Yuzhe, Wu Lingling, Wang Lifang, Gao Xingle, Li Yan, Fu Yaoyang, Jie Zhuye, Li Shenghui, Zhang Danhua, Chen Yiqing, Zhu Yiyi, Lu Shaojia, Lu Jing, Wang Dandan, Zhou Hetong, Yuan Xiuxia, Li Xue, Pang Lijuan, Huang Manli, Yang Huanming, Zhang Wenwei, Brix Susanne, Kristiansen Karsten, Song Xueqin, Nie Chao, Hu Shaohua
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
BGI-Shenzhen, Shenzhen, 518083, China.
Mol Psychiatry. 2022 Oct;27(10):4123-4135. doi: 10.1038/s41380-022-01569-9. Epub 2022 Apr 20.
The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.
微生物群-肠道-大脑在调节人类认知和情绪方面的复杂过程，尤其是在情绪障碍的背景下，一直难以捉摸。在这里，我们对109名未接受药物治疗的双相情感障碍（BD）抑郁症患者和40名健康对照（HC）进行了粪便宏基因组学、血清代谢组学和神经影像学研究，以表征BD中的微生物-肠道-大脑轴。在超过12000个测量的代谢特征中，我们观察到BD患者和HC之间血清代谢组存在很大差异（73.54%），发现了差异丰富的微生物衍生神经活性代谢物，包括多种B族维生素、犬尿烯酸、γ-氨基丁酸和短链脂肪酸。这些代谢物可能与具有相应生物合成潜力的肠道微生物群的丰度有关，包括嗜黏蛋白阿克曼氏菌、柠檬酸杆菌属（弗氏柠檬酸杆菌和韦氏柠檬酸杆菌）、考拉杆菌属、耶尔森菌属（弗雷德里克森耶尔森菌和亚历克西亚耶尔森菌）、肠杆菌属（阴沟肠杆菌和科贝肠杆菌）和黄杆菌属。基于功能神经影像学，发现与BD相关的神经活性微生物和代谢物是与大脑网络功能连接的BD典型特征相关的潜在标志物，暗示认知功能、情绪调节和内感受异常。我们的研究将肠道微生物群和神经活性代谢物与大脑功能连接相结合，从而揭示了从微生物群到肠道和大脑的潜在信号通路，这可能在BD的病理生理学中起作用。
