Gut microbes shape microglia and cognitive function during malnutrition
| dc.contributor.author | Han, Jun | |
| dc.contributor.author | Bauer, Kylynda C. | |
| dc.contributor.author | York, Elisa M. | |
| dc.contributor.author | Cirstea, Mihai S. | |
| dc.contributor.author | Radisavljevic, Nina | |
| dc.contributor.author | Petersen, Charisse | |
| dc.contributor.author | Huus, Kelsey E. | |
| dc.contributor.author | Brown, Eric M. | |
| dc.contributor.author | Bozorgmehr, Tahereh | |
| dc.contributor.author | Berdun, Rebeca | |
| dc.contributor.author | Bernier, Louis-Philippe | |
| dc.contributor.author | Lee, Amy H. Y. | |
| dc.contributor.author | Woodward, Sarah E. | |
| dc.contributor.author | Krekhno, Zakhar | |
| dc.contributor.author | Hancock, Robert E. W. | |
| dc.contributor.author | Ayala, Victoria | |
| dc.contributor.author | MacVicar, Brian A. | |
| dc.contributor.author | Finlay, Barton Brett | |
| dc.date.accessioned | 2022-02-23T23:06:50Z | |
| dc.date.available | 2022-02-23T23:06:50Z | |
| dc.date.copyright | 2022 | en_US |
| dc.date.issued | 2022-01-12 | |
| dc.description.abstract | Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood–brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target. | en_US |
| dc.description.reviewstatus | Reviewed | en_US |
| dc.description.scholarlevel | Faculty | en_US |
| dc.description.sponsorship | Bill and Melinda Gates Foundation Canadian Institute for Advanced Research Canadian Institutes of Health Research. Grant Number: FDN-159935 Leducq Foundation Departament de Salut, Generalitat de Catalunya | en_US |
| dc.identifier.citation | Bauer, K. C., York, E. M., Cirstea, M. S., Radisavljevic, N., Petersen, C., Huus, K. E., Brown, E. M., Bozorgmehr, T., Berdún, R., Bernier, L.-P., Lee, A. H. Y., Woodward, S. E., Krekhno, Z., Han, J., Hancock, R. E. W., Ayala, V., MacVicar, B. A., & Finlay, B. B. (2022). Gut microbes shape microglia and cognitive function during malnutrition. Glia, 1– 22. https://doi.org/10.1002/glia.24139 | en_US |
| dc.identifier.uri | https://doi.org/10.1002/glia.24139 | |
| dc.identifier.uri | http://hdl.handle.net/1828/13752 | |
| dc.language.iso | en | en_US |
| dc.publisher | GLIA | en_US |
| dc.subject | behavior | |
| dc.subject | gut-brain axis | |
| dc.subject | malnutrition | |
| dc.subject | microbiome | |
| dc.subject | microglia | |
| dc.subject | neurometabolism | |
| dc.subject | The Metabolomics Innovation Centre | |
| dc.subject.department | Division of Medical Sciences | |
| dc.subject.department | School of Medical Sciences | |
| dc.title | Gut microbes shape microglia and cognitive function during malnutrition | en_US |
| dc.type | Article | en_US |