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Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome
Author(s) -
Spychala Monica S.,
Venna Venugopal Reddy,
Jandzinski Michal,
Doran Sarah J.,
Durgan David J.,
Ganesh Bhanu Priya,
Ajami Nadim J.,
Putluri Nagireddy,
Graf Joerg,
Bryan Robert M.,
McCullough Louise D.
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25250
Subject(s) - dysbiosis , gut flora , firmicutes , stroke (engine) , inflammation , feces , young adult , medicine , immunology , pathogenesis , microbiome , physiology , biology , bioinformatics , microbiology and biotechnology , mechanical engineering , 16s ribosomal rna , bacteria , engineering , genetics
Objective Chronic systemic inflammation contributes to the pathogenesis of many age‐related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age‐related inflammation. Methods Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (middle cerebral artery occlusion; MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S ribosomal RNA analysis of bacterial content. Results We found that the microbiota is altered after experimental stroke in young mice and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9‐fold ( p < 0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6‐fold increase in F:B ratio, p < 0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (∼9‐fold decrease in F:B ratio, p < 0.001) increased survival and improved recovery following MCAO. Interpretation Aged biome increased the levels of systemic proinflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age‐related diseases. Ann Neurol 2018;83:23–36