Heterochronic fecal microbiota transfer reverses hallmarks of the aging gut, brain, and eye.

Parker A, Romano S, Ansorge R, Aboelnoer A, Le Gall G, Savva G, Telatin A, Jones E, Baker D, Rudder S, Blackshaw LA, Jeffery G, Carding S. (2022)

Microbiome

Background:       Altered intestinal microbiota composition in later life is associated with inflammaging and increased susceptibility to ageassociated chronic diseases affecting various organs. Here we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging, in particular, inflammation affecting the brain and retina. 
Methods:            Using heterochronic microbiota transplantation we exchanged the intestinal microbiota of young (3 month), old (18 month), and aged (24 month) mice.  We used whole metagenomic shotgun sequencing and metabolomics, and developed a custom analysis workflow, to analyze changes in gut microbiota composition and metabolic potential.  Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays and immunohistochemistry. 
Results:              We show ageassociated central nervous system (CNS) inflammation, and loss a of key functional protein in the eye, which are coincident with increased intestinal barrier permeability, are accelerated upon transfer of aged donor microbiota into young mice but are reversed by transfer of young donor microbiota to aged mice. 
Conclusions:      These findings demonstrate that the gut microbiota can mediate detrimental changes in the gutbrain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammatory tissue decline in later life. 

Microbiome

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