Format

Send to

Choose Destination
Ann Neurol. 2018 Jul;84(1):23-36. doi: 10.1002/ana.25250. Epub 2018 Jul 18.

Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

Author information

1
Department of Neurology, McGovern Medical School at University of Texas Health Science Center Houston, TX.
2
Department of Anesthesiology, University of Maryland, Baltimore, MD.
3
Department of Anesthesiology, Baylor College of Medicine, Houston, TX.
4
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX.
5
Dan L. Duncan Comprehensive Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
6
Department of Molecular and Cell Biology, Institute of Systems Genomics, University of Connecticut, Storrs, CT.

Abstract

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.

PMID:
29733457
PMCID:
PMC6119509
[Available on 2019-07-18]
DOI:
10.1002/ana.25250

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center