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Microbial shifts in the aging mouse gut.

Langille MG, Meehan CJ, Koenig JE, Dhanani AS, Rose RA, Howlett SE, Beiko RG - Microbiome (2014)

Bottom Line: 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.We observed a statistically significant relationship between age and the taxonomic composition of the corresponding 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia Canada ; Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia Canada.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Age (x-axis) and frailty index (y-axis) for the mice used in this study. Age correlated significantly with frailty index (Spearman correlation = 0.86, p = 1.064 × 10−5) and samples were derived from three age groupings: young (red), middle (blue), and old (green). Note that corresponding frailty scores were not performed for 4 of the 21 stool samples, so only 17 points are shown in the plot.
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Fig1: Age (x-axis) and frailty index (y-axis) for the mice used in this study. Age correlated significantly with frailty index (Spearman correlation = 0.86, p = 1.064 × 10−5) and samples were derived from three age groupings: young (red), middle (blue), and old (green). Note that corresponding frailty scores were not performed for 4 of the 21 stool samples, so only 17 points are shown in the plot.

Mentions: A total of 21 stool samples for metagenomic analysis were collected from ten different mice with varying ages and murine frailty index (FI) scores (Additional file 1). Age correlated with frailty (Spearman correlation = 0.86, p = 1.064 × 10−5), and fell into three natural groupings which we refer to as ‘young’ (age in days: mean 174 ± s.d. 15; FI: 0.024 ± 0.016; samples = 9; mice = 5), ‘middle’ (age in days: 589 ± 18; FI: 0.097 ± 0.030; samples = 6; mice = 2), and ‘old’ (age in days: 857 ± 16; FI: 0.302 ± 0.088, samples = 6; mice = 3) (Figure 1, Additional file 2). The strong correlation between FI and age reinforces that both are suitable measurements to compare with changes in the gut microbiome. Fares and Howlett showed that a 50% mortality rate occurs around 24 months in mice, which corresponds roughly to age 85 in humans [30]. Our study did not reveal a strong indication that either FI or age was a better predictor of microbiome shifts due to the sample size of the study and the lack of observed variation in FI with respect to age in this particular subset of mice.Figure 1


Microbial shifts in the aging mouse gut.

Langille MG, Meehan CJ, Koenig JE, Dhanani AS, Rose RA, Howlett SE, Beiko RG - Microbiome (2014)

Age (x-axis) and frailty index (y-axis) for the mice used in this study. Age correlated significantly with frailty index (Spearman correlation = 0.86, p = 1.064 × 10−5) and samples were derived from three age groupings: young (red), middle (blue), and old (green). Note that corresponding frailty scores were not performed for 4 of the 21 stool samples, so only 17 points are shown in the plot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4269096&req=5

Fig1: Age (x-axis) and frailty index (y-axis) for the mice used in this study. Age correlated significantly with frailty index (Spearman correlation = 0.86, p = 1.064 × 10−5) and samples were derived from three age groupings: young (red), middle (blue), and old (green). Note that corresponding frailty scores were not performed for 4 of the 21 stool samples, so only 17 points are shown in the plot.
Mentions: A total of 21 stool samples for metagenomic analysis were collected from ten different mice with varying ages and murine frailty index (FI) scores (Additional file 1). Age correlated with frailty (Spearman correlation = 0.86, p = 1.064 × 10−5), and fell into three natural groupings which we refer to as ‘young’ (age in days: mean 174 ± s.d. 15; FI: 0.024 ± 0.016; samples = 9; mice = 5), ‘middle’ (age in days: 589 ± 18; FI: 0.097 ± 0.030; samples = 6; mice = 2), and ‘old’ (age in days: 857 ± 16; FI: 0.302 ± 0.088, samples = 6; mice = 3) (Figure 1, Additional file 2). The strong correlation between FI and age reinforces that both are suitable measurements to compare with changes in the gut microbiome. Fares and Howlett showed that a 50% mortality rate occurs around 24 months in mice, which corresponds roughly to age 85 in humans [30]. Our study did not reveal a strong indication that either FI or age was a better predictor of microbiome shifts due to the sample size of the study and the lack of observed variation in FI with respect to age in this particular subset of mice.Figure 1

Bottom Line: 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.We observed a statistically significant relationship between age and the taxonomic composition of the corresponding 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia Canada ; Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia Canada.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus