An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria

Abstract

Interactions between bacteria and somatic cells are increasingly important for understanding cellular communication mechanisms. While the gut microbiome’s influence on the gut–brain axis is established, direct interactions between bacteria and neurons are poorly explored, especially regarding bidirectional information exchange. We developed an in vitro model using the foodborne bacterium Lactiplantibacillus plantarum and rat cortical neural cultures to study neuronal responses to bacterial presence through morphological, functional, and transcriptomic analyses. We found that L. plantarum adheres to neuronal surfaces without penetrating the soma. Real-time calcium imaging showed enhanced Ca2⁺ signaling dependent on bacterial concentration and active metabolism. Neurons exhibited changes in neuroplasticity-related proteins such as Synapsin I and pCREB, indicating functional modulation. Transcriptomic profiling revealed significant gene expression changes affecting networks linked to neurological conditions and bioelectrical signaling. Together, our results provide proof-of-concept for targeted neuronal responses induced by bacterial contact, offering key resources and transcriptomic data to advance the study of bacteria-driven neural modulation within the gut–brain axis.