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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The Characterization of Novel Tissue Microbiota Using an Optimized 16S Metagenomic Sequencing Pipeline
Jérôme Lluch,Florence Servant,Sandrine Païssé,Carine Valle,Sophie Valière,Claire Kuchly,Gaelle Vilchez,Cécile Donnadieu,Michael Courtney,Rémy Burcelin,Jacques Amar,Olivier Bouchez,Benjamin Lelouvier +12 more
TL;DR: This optimized 16S metagenomic sequencing pipeline will allow the scientific community to catalogue the bacterial DNA profiles of different tissues and will provide a database to analyse host/bacterial interactions in relation to homeostasis and disease.
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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease.
TL;DR: This review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.
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Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?
TL;DR: How to bridge transcriptional states to specific functions so the authors can develop therapies to mediate negative effects of altered microglia-astrocyte interactions is discussed.
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Gut Microbiota, Nitric Oxide, and Microglia as Prerequisites for Neurodegenerative Disorders
TL;DR: Pharmacological interventions and lifestyle modifications to rectify aberrant NO signaling in AD include NOS inhibitors, NMDA receptor antagonists, potassium channel modulators, probiotics, diet, and exercise.
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The role of gut microbiota in pathogenesis of Alzheimer's disease.
TL;DR: Three different linkages between the present gut microbiome hypothesis and the other major theories for the pathogenesis of AD are described as follows: bacterial metabolites and amyloids can trigger central nervous system inflammation and cerebrovascular degeneration; impaired gut microbiome flora inhibits the autophagy‐mediated protein clearance process; and gut microbiomes can change the neurotransmitter levels in the brain through the vagal afferent fibres.
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The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis
Patrick M. Smith,Michael R. Howitt,Nicolai Panikov,Monia Michaud,Carey Ann Gallini,Mohammad Bohlooly-Y,Jonathan N. Glickman,Wendy S. Garrett +7 more
TL;DR: This study determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice, revealing that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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