Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression

Research output: Contribution to journalJournal articlepeer-review

  • Zhiming Li
  • Jianbo Lai
  • Peifen Zhang
  • Jiahong Ding
  • Jiajun Jiang
  • Chuanfa Liu
  • Huimin Huang
  • Hefu Zhen
  • Caixi Xi
  • Yuzhe Sun
  • Lingling Wu
  • Lifang Wang
  • Xingle Gao
  • Yan Li
  • Yaoyang Fu
  • Zhuye Jie
  • Shenghui Li
  • Danhua Zhang
  • Yiqing Chen
  • Yiyi Zhu
  • Shaojia Lu
  • Jing Lu
  • Dandan Wang
  • Hetong Zhou
  • Xiuxia Yuan
  • Xue Li
  • Lijuan Pang
  • Manli Huang
  • Huanming Yang
  • Wenwei Zhang
  • Susanne Brix
  • Xueqin Song
  • Chao Nie
  • Shaohua Hu

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.

Original languageEnglish
JournalMolecular Psychiatry
Issue number1
Number of pages13
Publication statusPublished - 2022

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© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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