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 regardi...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-10382-7 |
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| author | Juan Lombardo-Hernandez Jesús Mansilla-Guardiola Riccardo Aucello Cristian Botta Maria Teresa García-Esteban Antonio Murciano-Cespedosa David Muñoz-Rodríguez Elisa Quarta Álvaro Mateos González Carmen Juan-Llamas Kalliopi Rantsiou Stefano Geuna Luca Cocolin Celia Herrera-Rincon |
| author_facet | Juan Lombardo-Hernandez Jesús Mansilla-Guardiola Riccardo Aucello Cristian Botta Maria Teresa García-Esteban Antonio Murciano-Cespedosa David Muñoz-Rodríguez Elisa Quarta Álvaro Mateos González Carmen Juan-Llamas Kalliopi Rantsiou Stefano Geuna Luca Cocolin Celia Herrera-Rincon |
| author_sort | Juan Lombardo-Hernandez |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7c79c84abaae48d692ab3dd8e63a5fa7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7c79c84abaae48d692ab3dd8e63a5fa72025-08-20T03:42:38ZengNature PortfolioScientific Reports2045-23222025-07-0115112210.1038/s41598-025-10382-7An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteriaJuan Lombardo-Hernandez0Jesús Mansilla-Guardiola1Riccardo Aucello2Cristian Botta3Maria Teresa García-Esteban4Antonio Murciano-Cespedosa5David Muñoz-Rodríguez6Elisa Quarta7Álvaro Mateos González8Carmen Juan-Llamas9Kalliopi Rantsiou10Stefano Geuna11Luca Cocolin12Celia Herrera-Rincon13Biomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridDepartment of Computer Science, University of TorinoDepartment of Agricultural, Forestry and Food Sciences, University of TurinUnit of Microbiology, Department of Genetic, Physiology and Microbiology, Biology Faculty, Complutense University of MadridBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridDepartment of Agricultural, Forestry and Food Sciences, University of TurinDepartment of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, Ospedale San Luigi, University of TurinDepartment of Agricultural, Forestry and Food Sciences, University of TurinBiomathematics Unit, Data Analysis and Computational Tools for Biology Research Group, Department of Biodiversity, Ecology and Evolution, and Modeling, Complutense University of MadridAbstract 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.https://doi.org/10.1038/s41598-025-10382-7Neurobacterial interactionMicrobiomeGut bacteriaBioelectricity |
| spellingShingle | Juan Lombardo-Hernandez Jesús Mansilla-Guardiola Riccardo Aucello Cristian Botta Maria Teresa García-Esteban Antonio Murciano-Cespedosa David Muñoz-Rodríguez Elisa Quarta Álvaro Mateos González Carmen Juan-Llamas Kalliopi Rantsiou Stefano Geuna Luca Cocolin Celia Herrera-Rincon An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria Scientific Reports Neurobacterial interaction Microbiome Gut bacteria Bioelectricity |
| title | An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria |
| title_full | An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria |
| title_fullStr | An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria |
| title_full_unstemmed | An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria |
| title_short | An in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria |
| title_sort | in vitro neurobacterial interface reveals direct modulation of neuronal function by gut bacteria |
| topic | Neurobacterial interaction Microbiome Gut bacteria Bioelectricity |
| url | https://doi.org/10.1038/s41598-025-10382-7 |
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