Young Versus Aged Microbiota Transplants to Germ-Free Mice: Increased Short-Chain Fatty Acids and Improved Cognitive Performance

Authors

Juneyoung Lee
Venugopal R Venna
David J Durgan
Huanan Shi
Jacob Hudobenko
Nagireddy Putluri
Joseph Petrosino
Louise D McCullough
Robert M Bryan

Publication Date

11-9-2020

Journal

Gut Microbes

DOI

10.1080/19490976.2020.1814107

PMID

32897773

PMCID

PMC7757789

PubMedCentral® Posted Date

9-8-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Aging, Animals, Bacteria, Brain, Cognition, Cognitive Dysfunction, Cytokines, Depression, Fatty Acids, Volatile, Fecal Microbiota Transplantation, Feces, Gastrointestinal Microbiome, Germ-Free Life, Leukocytes, Male, Memory, Mice, Mice, Inbred C57BL, T-Lymphocyte Subsets, Aging, gut microbiome, short-chain fatty acids, acetate, propionate, butyrate, inflammation, germ-free mice, cognitive decline

Abstract

Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline. Fecal transplant gavages (FTGs) from aged (18–20 months) or young (2–3 months) male C57BL/6 mice into germ-free male C57BL/6 mice (N = 11 per group) were initiated at ~3 months of age. Fecal samples were collected and behavioral testing was performed over the study period. Bacterial community structures and relative abundances were measured in fecal samples by sequencing the bacterial 16S ribosomal RNA gene. Mice with aged and young microbiomes showed clear differences in bacterial β diversity at 30, 60, and 90 d (P = .001 for each) after FTGs. The fecal SCFAs, acetate, propionate, and butyrate (microbiome effect, P < .01 for each) were decreased in mice with an aged microbiome. Mice with an aged microbiome demonstrated depressive-like behavior, impaired short-term memory, and impaired spatial memory over the 3 months following the initial FTG as assessed by the tail suspension (P = .008), the novel object recognition (P < .001), and the Barnes Maze (P = .030) tests, respectively. We conclude that an aged microbiome alone is sufficient to decrease SCFAs in the host and to produce cognitive decline.

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