Yes / Background: The changes that occur in the microbiome of aging individuals are unclear, especially in light of the
imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these
results may be confounded by other variables that often change with age such as diet and place of residence. To
test these associations in a more controlled model system, we examined the relationship between age, frailty, and
the gut microbiome of female C57BL/6 J mice.
Results: The frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a
near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic
composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family,
which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and
older mice.
The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded
functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis,
and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting,
was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which
can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide
utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on
gut homeostasis.
Conclusion: We have identified taxonomic and functional patterns that correlate with age and frailty in the mouse
microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent
manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty.
Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors. / This work was supported by the Canadian Institutes of Health Research (CIHR) through an Emerging Team Grant to RGB, CIHR Operating Grants to Langille et al. Microbiome 2014, 2:50 Page 10 of 12 http://www.microbiomejournal.com/content/2/1/50 SEH (MOP 126018) and RAR (MOP 93718), and a CIHR Fellowship to MGIL. Infrastructure was supported by the Canada Foundation for Innovation through a grant to RGB. RGB also acknowledges the support of the Canada Research Chairs program.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/17290 |
| Date | 24 September 2019 |
| Creators | Langille, M.G.I., Meehan, Conor J., Koenig, J.E., Dhanani, A.S., Rose, R.A., Howlett, S.E., Beiko, R.G. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © 2014 Langille et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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