Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia.
Bilophila
brain
cognition
hippocampus
microbiota
neuroimmune
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 09 2021
08 09 2021
Historique:
received:
21
01
2021
revised:
17
05
2021
accepted:
12
07
2021
pubmed:
7
8
2021
medline:
14
1
2022
entrez:
6
8
2021
Statut:
ppublish
Résumé
Many genetic and environmental factors increase susceptibility to cognitive impairment (CI), and the gut microbiome is increasingly implicated. However, the identity of gut microbes associated with CI risk, their effects on CI, and their mechanisms remain unclear. Here, we show that a carbohydrate-restricted (ketogenic) diet potentiates CI induced by intermittent hypoxia in mice and alters the gut microbiota. Depleting the microbiome reduces CI, whereas transplantation of the risk-associated microbiome or monocolonization with Bilophila wadsworthia confers CI in mice fed a standard diet. B. wadsworthia and the risk-associated microbiome disrupt hippocampal synaptic plasticity, neurogenesis, and gene expression. The CI is associated with microbiome-dependent increases in intestinal interferon-gamma (IFNg)-producing Th1 cells. Inhibiting Th1 cell development abrogates the adverse effects of both B. wadsworthia and environmental risk factors on CI. Together, these findings identify select gut bacteria that contribute to environmental risk for CI in mice by promoting inflammation and hippocampal dysfunction.
Identifiants
pubmed: 34358434
pii: S1931-3128(21)00337-1
doi: 10.1016/j.chom.2021.07.004
pmc: PMC8429275
mid: NIHMS1731552
pii:
doi:
Substances chimiques
IFNG protein, mouse
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1378-1392.e6Subventions
Organisme : NINDS NIH HHS
ID : F31 NS118966
Pays : United States
Organisme : NIMH NIH HHS
ID : F31 MH090749
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG064844
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS115537
Pays : United States
Organisme : NICHD NIH HHS
ID : F31 HD101270
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007185
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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