Zhao Dianshu, Shiga Russel T, Song Zhangrong, Shu Runhang, Loo Lipin, Wong Adam Chun Nin
Entomology and Nematology Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
School of Life and Environmental Sciences and the Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
NPJ Biofilms Microbiomes. 2025 Aug 12;11(1):162. doi: 10.1038/s41522-025-00781-z.
The gut microbiome plays a critical role in brain function and the brain-gut axis, yet its cellular and molecular mechanisms remain unclear. Here, we present the first comprehensive single-cell transcriptomic atlas of brain cells from adult Drosophila melanogaster raised under axenic and microbiome-associated conditions, spanning young and old ages. Profiling 34,427 cells across 101 clusters, we annotated 56 cell types and identified cell type-specific gene signatures influenced by the microbiome. Transcriptional shifts were most pronounced in old flies, with glial cells and dopaminergic neurons among the most microbiome-responsive cell types. Differentially expressed genes (DEGs) were enriched in pathways related to mitochondrial activity, energy metabolism, and Notch signaling. We also quantified age-associated changes in the gut microbiome, observing reduced Acetobacter dominance and increased microbial diversity that corresponded with heightened brain transcriptional responses. These findings illuminate the cell type-specific impacts of the microbiome on brain gene expression and lay the groundwork for understanding the molecular underpinnings of the microbiome-gut-brain axis.
肠道微生物群在大脑功能和脑-肠轴中起着关键作用，但其细胞和分子机制仍不清楚。在这里，我们展示了首个全面的单细胞转录组图谱，该图谱涵盖了在无菌和与微生物群相关条件下饲养的成年黑腹果蝇不同年龄段的脑细胞。通过对101个细胞簇中的34427个细胞进行分析，我们注释了56种细胞类型，并确定了受微生物群影响的细胞类型特异性基因特征。转录变化在老年果蝇中最为明显，神经胶质细胞和多巴胺能神经元是对微生物群反应最敏感的细胞类型。差异表达基因（DEGs）在与线粒体活性、能量代谢和Notch信号通路相关的途径中富集。我们还量化了肠道微生物群与年龄相关的变化，观察到醋杆菌优势度降低和微生物多样性增加，这与大脑转录反应增强相对应。这些发现揭示了微生物群对大脑基因表达的细胞类型特异性影响，并为理解微生物群-肠-脑轴的分子基础奠定了基础。
