Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila
Abstract 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 mi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-025-00781-z |
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| author | Dianshu Zhao Russel T. Shiga Zhangrong Song Runhang Shu Lipin Loo Adam Chun Nin Wong |
| author_facet | Dianshu Zhao Russel T. Shiga Zhangrong Song Runhang Shu Lipin Loo Adam Chun Nin Wong |
| author_sort | Dianshu Zhao |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-25da213a3bdb49c6b3fafc9dbf17070a |
| institution | Kabale University |
| issn | 2055-5008 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj-art-25da213a3bdb49c6b3fafc9dbf17070a2025-08-20T03:42:34ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-08-0111111110.1038/s41522-025-00781-zMicrobiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in DrosophilaDianshu Zhao0Russel T. Shiga1Zhangrong Song2Runhang Shu3Lipin Loo4Adam Chun Nin Wong5Entomology and Nematology Department, Institute of Food and Agricultural Sciences, University of FloridaEntomology and Nematology Department, Institute of Food and Agricultural Sciences, University of FloridaEntomology and Nematology Department, Institute of Food and Agricultural Sciences, University of FloridaEntomology and Nematology Department, Institute of Food and Agricultural Sciences, University of FloridaSchool of Life and Environmental Sciences and the Charles Perkins Centre, The University of SydneyEntomology and Nematology Department, Institute of Food and Agricultural Sciences, University of FloridaAbstract 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.https://doi.org/10.1038/s41522-025-00781-z |
| spellingShingle | Dianshu Zhao Russel T. Shiga Zhangrong Song Runhang Shu Lipin Loo Adam Chun Nin Wong Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila npj Biofilms and Microbiomes |
| title | Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila |
| title_full | Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila |
| title_fullStr | Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila |
| title_full_unstemmed | Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila |
| title_short | Microbiome drives age-dependent shifts in brain transcriptomic programs at the single-cell level in Drosophila |
| title_sort | microbiome drives age dependent shifts in brain transcriptomic programs at the single cell level in drosophila |
| url | https://doi.org/10.1038/s41522-025-00781-z |
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