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Gut microbes shape microglia and cognitive function during malnutrition.
Bauer, Kylynda C; York, Elisa M; Cirstea, Mihai S; Radisavljevic, Nina; Petersen, Charisse; Huus, Kelsey E; Brown, Eric M; Bozorgmehr, Tahereh; Berdún, Rebeca; Bernier, Louis-Philippe; Lee, Amy H Y; Woodward, Sarah E; Krekhno, Zakhar; Han, Jun; Hancock, Robert E W; Ayala, Victoria; MacVicar, Brian A; Finlay, Barton Brett.
Affiliation
  • Bauer KC; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • York EM; Microbiology and Immunology Department, University of British Columbia, Vancouver, Canada.
  • Cirstea MS; Psychiatry Department, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.
  • Radisavljevic N; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • Petersen C; Microbiology and Immunology Department, University of British Columbia, Vancouver, Canada.
  • Huus KE; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • Brown EM; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, Canada.
  • Bozorgmehr T; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • Berdún R; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • Bernier LP; Microbiology and Immunology Department, University of British Columbia, Vancouver, Canada.
  • Lee AHY; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • Woodward SE; Microbiology and Immunology Department, University of British Columbia, Vancouver, Canada.
  • Krekhno Z; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
  • Han J; Institut de Recerca Biomèdica de Lleida (IRB-Lleida), Lleida, Spain.
  • Hancock REW; Department of Experimental Medicine, Universitat de Lleida (UdL), Lleida, Spain.
  • Ayala V; Psychiatry Department, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.
  • MacVicar BA; Microbiology and Immunology Department, University of British Columbia, Vancouver, Canada.
  • Finlay BB; Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
Glia ; 70(5): 820-841, 2022 05.
Article in En | MEDLINE | ID: mdl-35019164
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.
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Malnutrition / Gastrointestinal Microbiome Type of study: Prognostic_studies Aspects: Determinantes_sociais_saude Limits: Animals Language: En Journal: Glia Year: 2022 Document type: Article
Fulltext
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XML
PubMed Links
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Malnutrition / Gastrointestinal Microbiome Type of study: Prognostic_studies Aspects: Determinantes_sociais_saude Limits: Animals Language: En Journal: Glia Year: 2022 Document type: Article