Bacteria invade the brain following intracortical microelectrode implantation, inducing gut-brain axis disruption and contributing to reduced microelectrode performance

George F. Hoeferlin, Sarah E. Grabinski, Lindsey N. Druschel, Jonathan L. Duncan, Grace Burkhart, Gwendolyn R. Weagraff, Alice H. Lee, Christopher Hong, Meera Bambroo, Hannah Olivares, Tejas Bajwa, Jennifer Coleman, Longshun Li, William Memberg, Jennifer Sweet, Hoda Amani Hamedani, Abhinav P. Acharya, Ana G. Hernandez-Reynoso, Curtis Donskey, George Jaskiw, E. Ricky Chan, Andrew J. Shoffstall, A. Bolu Ajiboye, Horst A. Recum, Liangliang Zhang () and Jeffrey R. Capadona ()
Additional contact information
George F. Hoeferlin: Case Western Reserve University
Sarah E. Grabinski: Case Western Reserve University
Lindsey N. Druschel: Case Western Reserve University
Jonathan L. Duncan: Case Western Reserve University
Grace Burkhart: Case Western Reserve University
Gwendolyn R. Weagraff: Louis Stokes Cleveland Department of Veterans Affairs Medical Center
Alice H. Lee: Case Western Reserve University
Christopher Hong: Case Western Reserve University
Meera Bambroo: Case Western Reserve University
Hannah Olivares: Case Western Reserve University
Tejas Bajwa: Case Western Reserve University
Jennifer Coleman: Case Western Reserve University
Longshun Li: Case Western Reserve University
William Memberg: Case Western Reserve University
Jennifer Sweet: Louis Stokes Cleveland Department of Veterans Affairs Medical Center
Hoda Amani Hamedani: Louis Stokes Cleveland Department of Veterans Affairs Medical Center
Abhinav P. Acharya: Case Western Reserve University
Ana G. Hernandez-Reynoso: Case Western Reserve University
Curtis Donskey: Louis Stokes Cleveland Department of Veterans Affairs Medical Center
George Jaskiw: Louis Stokes Cleveland Department of Veterans Affairs Medical Center
E. Ricky Chan: Case Western Reserve University
Andrew J. Shoffstall: Case Western Reserve University
A. Bolu Ajiboye: Case Western Reserve University
Horst A. Recum: Case Western Reserve University
Liangliang Zhang: Case Western Reserve University
Jeffrey R. Capadona: Case Western Reserve University

Nature Communications, 2025, vol. 16, issue 1, 1-27

Abstract: Abstract Brain-machine interface performance can be affected by neuroinflammatory responses due to blood-brain barrier (BBB) damage following intracortical microelectrode implantation. Recent findings suggest that certain gut bacterial constituents might enter the brain through damaged BBB. Therefore, we hypothesized that damage to the BBB caused by microelectrode implantation could facilitate microbiome entry into the brain. In our study, we found bacterial sequences, including gut-related ones, in the brains of mice with implanted microelectrodes. These sequences changed over time. Mice treated with antibiotics showed a reduced presence of these bacteria and had a different inflammatory response, which temporarily improved microelectrode recording performance. However, long-term antibiotic use worsened performance and disrupted neurodegenerative pathways. Many bacterial sequences found were not present in the gut or in unimplanted brains. Together, the current study established a paradigm-shifting mechanism that may contribute to chronic intracortical microelectrode recording performance and affect overall brain health following intracortical microelectrode implantation.

Date: 2025
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DOI: 10.1038/s41467-025-56979-4

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