Heterochronic Fecal Microbiota Transfer Reverses Hallmarks of the Aging Murine Gut, Eye and Brain

Abstract

Altered intestinal microbiota composition in later life is associated with inflammaging and increased susceptibility to age–associated chronic diseases affecting various organs. Here we tested the hypothesis that manipulating the intestinal microbiota influences the development of comorbidities associated with aging, in particular, inflammation affecting intestinal epithelial barrier integrity, the retina, and the brain. Using heterochronic microbiota transplantation to exchange the intestinal microbiota of young (3 month), old (18 month), and aged (24 month) mice, we show that age–associated increases in intestinal barrier permeability, central nervous system (CNS) inflammation, and loss a of key functional retinal protein, are reversed by transfer of young donor microbiota to aged mice, but are accelerated upon transfer of aged donor microbiota into young mice. These findings demonstrate that the aged microbiota composition mediates detrimental changes in the gut–CNS axis, and suggest that microbial modulation may be of therapeutic benefit in later life.