Gut microbes shape microglia and cognitive function during malnutrition

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dc.contributor.authorBauer, Kylynda C.
dc.contributor.authorYork, Elisa M.
dc.contributor.authorCirstea, Mihai
dc.contributor.authorRadisavljevic, Nina
dc.contributor.authorPetersen, Charisse
dc.contributor.authorHuus, Kelsey E.
dc.contributor.authorBrown, Eric M.
dc.contributor.authorBozorgmehr, Tahereh
dc.contributor.authorBerdún Hernández, Rebeca
dc.contributor.authorBernier, Louis-Philippe
dc.contributor.authorLee, Amy H.Y.
dc.contributor.authorWoodward, Sarah E.
dc.contributor.authorKrekhno, Zakhar
dc.contributor.authorHan, Jun
dc.contributor.authorHancock, Robert E.W.
dc.contributor.authorAyala Jové, Ma. Victoria (Maria Victoria)
dc.contributor.authorMacVicar, Brian A.
dc.contributor.authorFinlay, Barton Brett
dc.date.accessioned2022-03-23T08:50:12Z
dc.date.available2022-03-23T08:50:12Z
dc.date.issued2022
dc.description.abstractFecal-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.ca_ES
dc.identifier.doihttps://doi.org/10.1002/glia.24139
dc.identifier.idgrec032692
dc.identifier.issn0894-1491
dc.identifier.issn1098-1136
dc.identifier.urihttp://hdl.handle.net/10459.1/73374
dc.language.isoengca_ES
dc.publisherWiley Periodicalsca_ES
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1002/glia.24139ca_ES
dc.relation.ispartofGlia, 2022, vol. 70, núm. 5, p. 820-841ca_ES
dc.rightscc-by (c)Authors, 2022ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBehaviorca_ES
dc.subjectGut-brain axisca_ES
dc.subjectMalnutritionca_ES
dc.subjectMicrobiomeca_ES
dc.subjectMicrogliaca_ES
dc.subjectNeurometabolismca_ES
dc.titleGut microbes shape microglia and cognitive function during malnutritionca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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