2. Academic Validation
  3. Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis

Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis

  • Cell Rep. 2025 Mar 25;44(3):115356. doi: 10.1016/j.celrep.2025.115356.
Samantha M Golomb 1,  Ian H Guldner 2,  Emilija Aleksandrovic 1,  Shaneann R Fross 1,  Xiyu Liu 1,  Lu Diao 3,  Karena Liang 4,  Jinxuan Wu 4,  Qingfei Wang 2,  Jacqueline A Lopez 5,  Siyuan Zhang 6
Affiliations

Affiliations

  • 1 Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, Dallas, TX 75390, USA; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, 1234 N. Notre Dame Avenue, South Bend, IN 46617, USA.
  • 2 Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, 1234 N. Notre Dame Avenue, South Bend, IN 46617, USA.
  • 3 Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, Dallas, TX 75390, USA.
  • 4 Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5 Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA.
  • 6 Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, Dallas, TX 75390, USA; Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, 1234 N. Notre Dame Avenue, South Bend, IN 46617, USA. Electronic address: siyuan.zhang@utsouthwestern.edu.
PMID: 40023843 DOI: 10.1016/j.celrep.2025.115356
Abstract

Interactions between metastatic Cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell Sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.

Keywords

CP: Cancer; CP: Microbiology; brain metastasis; cancer; gut microbiome; single cell RNA sequencing.

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