Controlled manipulation of the gut microbiome improves intracortical microelectrode performance

Intracortical microelectrode arrays (MEAs) record neuronal action potentials in the brain and can be paired with external systems to provide motor function rehabilitation to those with disabilities. Unfortunately, recording quality of MEAs consistently declines over the course of weeks to months compromising device utility. Neuroinflammation from persistent indwelling of MEAs is considered a significant contributor to the decline in recording performance. Recent evidence suggests that the gut microbiome may play a role in brain health possibly via bacteria-specific metabolites or microbiota infiltrating through the blood-brain barrier. Therefore, we hypothesize that altering the gut microbiome in mice via oral antibiotics or probiotics could change the microbiome composition in both the brain and gut, affecting neuroinflammation and MEA performance. Here, mice implanted with an MEA device for 12 weeks were treated with either antibiotics, probiotics, or normal diet to modulate gut microbiome composition. Biweekly neural recording sessions indicated temporal differences in MEA recording performance. Acutely (Weeks 1-5), antibiotic-treated mice (79% active electrode yield, AEY) and probiotic-treated mice (74% AEY) showed significantly better MEA performance than control (69% AEY). Probiotic significantly outperformed antibiotic sub-chronically (Weeks 6-11) and chronically (Weeks 12+). Differential changes to 16S RNA composition in stool and brain tissue suggested treatment-specific changes at the neural implant site. Culturing of explanted brain tissue indicated that live gut-derived bacteria were differentially found in the brain after implantation and treatment. Transcriptomic and proteomic analysis on brain tissue is underway to understand the correlation between MEA performance, microbiome composition, and neuroinflammation following MEA implantation and treatment. At minimum, our data suggest a connection between microbiome composition and recording performance. Such evidence provides a novel means for understanding and improving the lifetime of MEA devices to be used chronically in humans.