Multi-omics analysis of gut-brain axis reveals novel microbial and neurotransmitter signatures in patients with arteriosclerotic cerebral small vessel disease
Jiayuan Huang, Sanxin Liu, Peijie Li, Lei Wei, Lin Gan, Jiahao Lin, Yuting Luo, Yixin Liu, Yudan Mao, Hengfang Ruan, Bing Qin, Ping Fan, Tingting Lü, Wei Cai, Haotong Yi, Xiangyu Mou, Zhengqi Lu, Wenjing Zhao, Aimin Wu
Abstract
Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis , alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target. • Patients with aCSVD exhibited a decrease in Faecalibacterium prausnitzli and an increase in Bacteroides and Proteobacteria. • Alterations in LPS biosynthesis and phenylalanine-tyrosine metabolism were associated with aCSVD. • Microbial LPS and phenylalanine-tyrosine metabolism may influence aCSVD symptoms via inflammatory and neurotransmitter pathways. • A Support Vector Machine model effectively predicted aCSVD status using gut microbiota data. • Faecalibacterium prausnitzli and Roseburia intestinalis may be developed as live biotherapeutic products against aCSVD.