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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis.
TL;DR: The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease, where the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.
Journal ArticleDOI
Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry
Kiran V. Sandhu,Eoin Sherwin,Harriët Schellekens,Catherine Stanton,Timothy G. Dinan,John F. Cryan +5 more
TL;DR: The microbiota is poised to play a key role in nutritional interventions for maintaining brain health and diet composition and nutritional status has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions.
Journal ArticleDOI
Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis
Luisa Möhle,Daniele Mattei,Markus M. Heimesaat,Stefan Bereswill,André Fischer,Marie E. Alutis,Timothy French,Dolores Hambardzumyan,Dolores Hambardzumyan,Polly Matzinger,Ildiko Rita Dunay,Susanne A. Wolf +11 more
TL;DR: It is proposed that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6C(hi) monocytes.
Journal ArticleDOI
CNS inflammation and neurodegeneration.
Tanuja Chitnis,Howard L. Weiner +1 more
TL;DR: This Review focuses on the mechanisms by which inflammation, mediated either by the peripheral immune response or by endogenous CNS immune mechanisms, can affect CNS neurodegeneration.
Journal ArticleDOI
Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.
Kathryn M. Lenz,Lars H. Nelson +1 more
TL;DR: This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglial cells during development are distinct from microglian cells later in life.
References
More filters
Journal ArticleDOI
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Journal ArticleDOI
The gut microbiota shapes intestinal immune responses during health and disease
TL;DR: Findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut are discussed, and the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms is raised.
Journal ArticleDOI
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Florent Ginhoux,Florent Ginhoux,Melanie Greter,Marylene Leboeuf,Sayan Nandi,Peter See,Solen Gokhan,Mark F. Mehler,Simon J. Conway,Lai Guan Ng,E. Richard Stanley,Igor M. Samokhvalov,Miriam Merad +12 more
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
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.
Journal ArticleDOI
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eran Eden,Roy Navon,Roy Navon,Israel Steinfeld,Israel Steinfeld,Doron Lipson,Zohar Yakhini,Zohar Yakhini +7 more
TL;DR: GOrilla is a web-based application that identifies enriched GO terms in ranked lists of genes, without requiring the user to provide explicit target and background sets, and its unique features and advantages over other threshold free enrichment tools include rigorous statistics, fast running time and an effective graphical representation.
Related Papers (5)
The gut microbiota influences blood-brain barrier permeability in mice
Viorica Braniste,Maha Al-Asmakh,Czeslawa Kowal,Farhana Anuar,Afrouz Abbaspour,Miklós Tóth,Agata Korecka,Nadja Bakocevic,Lai Guan Ng,Parag Kundu,Balázs Gulyás,Balázs Gulyás,Christer Halldin,Christer Halldin,Kjell Hultenby,Harriet Nilsson,Hans Hebert,Bruce T. Volpe,Betty Diamond,Sven Pettersson,Sven Pettersson +20 more
Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease
Timothy R. Sampson,Justine W. Debelius,Taren Thron,Stefan Janssen,Gauri G. Shastri,Zehra Esra Ilhan,Collin Challis,Catherine E. Schretter,Sandra Rocha,Viviana Gradinaru,Marie-Françoise Chesselet,Ali Keshavarzian,Kathleen M. Shannon,Rosa Krajmalnik-Brown,Pernilla Wittung-Stafshede,Rob Knight,Sarkis K. Mazmanian +16 more