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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Microbiota modulation as preventative and therapeutic approach in Alzheimer's disease.
Laura Bonfili,Valentina Cecarini,Olee Gogoi,Chunmei Gong,Massimiliano Cuccioloni,Mauro Angeletti,Giacomo Rossi,Anna Maria Eleuteri +7 more
TL;DR: The role of gut microbiota in AD is dissected and recent advances in the development of new multitarget strategies for microbiota modulation to be used as possible preventative and therapeutic approaches in AD are highlighted.
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Can the gut be the missing piece in uncovering PD pathogenesis
Guillaume Chapelet,Laurène Leclair-Visonneau,Thomas Clairembault,Michel Neunlist,Pascal Derkinderen +4 more
TL;DR: Clinical and pathological evidence suggesting that the gut-brain axis is dysfunctional in PD is presented by discussing the possible role of gut microbiota, inflammation and permeability in the development of the disease.
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Microbial Immuno-Communication in Neurodegenerative Diseases.
Bevan S. Main,Myles R. Minter +1 more
TL;DR: Insight is provided into the regulation of neuro-inflammatory processes by the host microbiome in the context of neurodegenerative disease and the potential importance of the blood- brain barrier and blood-cerebrospinal fluid-brain barrier, functioning as “immune barriers,” to communicate host immune status to the brain is highlighted.
Journal ArticleDOI
The gut, its microbiome, and the brain: connections and communications
TL;DR: The existence of a microbiota-gut-brain "connectome" has become apparent and the interaction between the microbiota, the bowel, and the brain now appears to be neither a top-down nor a bottom-up process as mentioned in this paper.
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Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders.
TL;DR: Light is shed on the advent of myeloablation and how it allowed deciphering the ontology of microglia and its maintenance during adulthood and the different strategies used to perform myeloABlation are compared.
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Journal ArticleDOI
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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