Host microbiota constantly control maturation and function of microglia in the CNS
Daniel Erny,Anna Lena Hrabě de Angelis,Diego Jaitin,Peter Wieghofer,Ori Staszewski,Eyal David,Hadas Keren-Shaul,Tanel Mahlakõiv,Kristin Jakobshagen,Thorsten Buch,Vera Schwierzeck,Olaf Utermöhlen,Eunyoung Chun,Wendy S. Garrett,Kathy D. McCoy,Andreas Diefenbach,Peter Staeheli,Bärbel Stecher,Ido Amit,Marco Prinz +19 more
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TLDR
It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.Abstract:
As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.read more
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Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model.
Yang Shi,Melissa Manis,Justin M. Long,Kairuo Wang,Patrick Sullivan,Javier Remolina Serrano,Rosa Hoyle,David M. Holtzman +7 more
TL;DR: It is found that microglia, instead of tau-induced direct neurotoxicity, are the driving force of neurodegeneration in a tauopathy mouse model and apoE strongly regulates neurodegenersation in the setting of tAUopathy predominantly by modulating microglial function.
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Host-microbiota interactions in immune-mediated diseases.
TL;DR: The mechanisms through which the microbiota contributes to the predisposition, initiation and perpetuation of immune-mediated diseases, and the therapeutic avenues that either target the microbiota, the barrier surfaces or the host immune system to restore tolerance and homeostasis are discussed.
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Fecal Microbiota Transplantation in Neurological Disorders.
Karuna E. W. Vendrik,Rogier E. Ooijevaar,Rogier E. Ooijevaar,Pieter R. C. de Jong,Jon D. Laman,Bob W. van Oosten,Jacobus J. van Hilten,Quinten R Ducarmon,Josbert J. Keller,E.J. Kuijper,Maria Fiorella Contarino +10 more
TL;DR: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders, however, available evidence is still scanty and some contrasting results were observed.
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Author Correction: Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Hannah Iaccarino,Annabelle C. Singer,Anthony J Martorell,Anthony J Martorell,Andrii Rudenko,Andrii Rudenko,Andrii Rudenko,Fan Gao,Fan Gao,Tyler Z. Gillingham,Tyler Z. Gillingham,Hansruedi Mathys,Hansruedi Mathys,Jinsoo Seo,Jinsoo Seo,Oleg Kritskiy,Oleg Kritskiy,Fatema Abdurrob,Fatema Abdurrob,Chinnakkaruppan Adaikkan,Chinnakkaruppan Adaikkan,Rebecca G. Canter,Rebecca G. Canter,Richard Rueda,Richard Rueda,Emery N. Brown,Edward S. Boyden,Edward S. Boyden,Li-Huei Tsai,Li-Huei Tsai,Li-Huei Tsai +30 more
TL;DR: Reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer’s disease uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
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Sex differences in the gut microbiome-brain axis across the lifespan.
TL;DR: The sexually dimorphic development, maturation and maintenance of the gut microbiome–brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan are discussed.
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