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Mid-Life Microbiota Crises: Middle Age is Associated with Pervasive Neuroimmune Alterations that are Reversed by Targeting the Gut Microbiome

Boehme M, van de Wouw M, Bastiaanssen TFS, Olavarría-Ramírez L, Lyons K, Fouhy F, Golubeva AV, Moloney GM, Minuto C, Sandhu KV, Scott KA, Clarke G, Stanton C, Dinan TG, Schellekens H, Cryan JF (2019) Mol Psychiatry.  2019 May 16.  doi: 10.1038/s41380-019-0425-1. [Epub ahead of print] 

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Abstract:

Male middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function.

However, the mechanisms underpinning such changes are unclear. The 
gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6Chi monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C+) was observed.

Taken together, these data highlight a potential pathway by which 
targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.

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