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–Host Transgenomic Metabolism, Bioactive Molecules from the Inside
TL;DR: Drug discovery targeting the gut microbiota as well as the characterization of microbiota-derived metabolites can represent innovative medicinal chemistry possibilities toward the identification of novel drug candidates, targets, and more in general innovative ways for the treatment of unmet medical needs.
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Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trial
TL;DR: It is demonstrated that colon-delivered SCFAs modulate hypothalamic-pituitary-adrenal axis reactivity to psychosocial stress, thereby supporting their hypothesized role in microbiota-gut-brain communication.
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Got worms? Perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection.
Lauren Williamson,Erin A. McKenney,Zoie E. Holzknecht,Christine Belliveau,John F. Rawls,Susan Poulton,William Parker,Staci D. Bilbo +7 more
TL;DR: It is demonstrated that helminth colonization of pregnant dams attenuated the exaggerated brain cytokine response of their offspring to bacterial infection, and that combined with post-weaning colonization of offspring with helminths completely prevented enduring microglial sensitization and cognitive dysfunction in adulthood.
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Of Microbes and Minds: A Narrative Review on the Second Brain Aging.
Riccardo Calvani,Anna Picca,Maria Rita Lo Monaco,Francesco Landi,Roberto Bernabei,Emanuele Marzetti +5 more
TL;DR: Although the most provoking data emerged from animal studies and despite the huge debate around the possible epiphenomenal nature of those findings, the gut microbiota–brain axis remains a fascinating target to be exploited to attenuate some of the most burdensome consequences of aging.
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Gut Microbiome Alterations Precede Cerebral Amyloidosis and Microglial Pathology in a Mouse Model of Alzheimer's Disease.
Yijing Chen,Lihua Fang,Shuo Chen,Haokui Zhou,Yingying Fan,Li Lin,Jing Li,Jinying Xu,Yuewen Chen,Yuewen Chen,Yingfei Ma,Yu Chen,Yu Chen +12 more
TL;DR: Gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation, and the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD.
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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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