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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

Taxonomic composition for the nine most abundant families determined using identified 16S sequences, across all 21 samples ordered by increasing age; increasing frailty in each group is ordered from left to right. For visual clarity, only the nine most abundant families are shown in the plot. Taxonomic ranks are indicated as follows: ‘k’, kingdom (or domain); ‘p’, phylum; ‘c’, class; ‘o’, order; ‘f’, family. The unspecified ‘f__’ represents those OTUs that do not have a specific family name but are known to be within the order Clostridiales.
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Fig3: Taxonomic composition for the nine most abundant families determined using identified 16S sequences, across all 21 samples ordered by increasing age; increasing frailty in each group is ordered from left to right. For visual clarity, only the nine most abundant families are shown in the plot. Taxonomic ranks are indicated as follows: ‘k’, kingdom (or domain); ‘p’, phylum; ‘c’, class; ‘o’, order; ‘f’, family. The unspecified ‘f__’ represents those OTUs that do not have a specific family name but are known to be within the order Clostridiales.

Mentions: Taxonomic differences were compared across the different age groups to determine if particular taxa are associated with the gut microbiomes of aging and frail mice. The Rikenellaceae family, which contains the Alistipes genus and has previously been linked to microbiomes from elderly people [22], was the most significantly overrepresented family within the middle and old groups in comparison to young mice when using 16S data (Kruskal-Wallis H test, Benjamini-Hochberg FDR multiple test correction p = 0.007) (Figure 3; Additional files 6 and 7). To ensure that this taxonomic link between frailer mice and people was not an artifact of using the 16S rRNA gene as a marker, an independent analysis using protein markers (PhyloSift) and phylogenetic placement (Pplacer) was conducted. The latter method has the advantage of identifying the phylogenetic context of sequenced reads but does not provide statistical significance testing. However, the results from this method did provide additional support that the Alistipes were more abundant within the old and middle mouse groups (Figure 4). The PhyloSift approach indicated that the old mice have lower abundances of organisms from the Lachnospiraceae family, a group often associated with the production of beneficial SCFAs [37], even though the 16S-based method did not show a significant difference (p = 0.7) between the age groups. This contrasting result suggests that the type of phylogenetic marker used for taxonomic assessment can give conflicting results for some taxon families. Lastly, the PhyloSift approach indicated that some members of the Bacteroidaceae family were abundant in the old and middle groups, while fewer were abundant in the young group, which did agree with the 16S results (old: 9.2% ± 7.9%; middle: 10.3% ± 1.3%; young: 3.9% ± 1.4%, p = 0.06).Figure 3


Microbial shifts in the aging mouse gut.

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

Taxonomic composition for the nine most abundant families determined using identified 16S sequences, across all 21 samples ordered by increasing age; increasing frailty in each group is ordered from left to right. For visual clarity, only the nine most abundant families are shown in the plot. Taxonomic ranks are indicated as follows: ‘k’, kingdom (or domain); ‘p’, phylum; ‘c’, class; ‘o’, order; ‘f’, family. The unspecified ‘f__’ represents those OTUs that do not have a specific family name but are known to be within the order Clostridiales.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Taxonomic composition for the nine most abundant families determined using identified 16S sequences, across all 21 samples ordered by increasing age; increasing frailty in each group is ordered from left to right. For visual clarity, only the nine most abundant families are shown in the plot. Taxonomic ranks are indicated as follows: ‘k’, kingdom (or domain); ‘p’, phylum; ‘c’, class; ‘o’, order; ‘f’, family. The unspecified ‘f__’ represents those OTUs that do not have a specific family name but are known to be within the order Clostridiales.
Mentions: Taxonomic differences were compared across the different age groups to determine if particular taxa are associated with the gut microbiomes of aging and frail mice. The Rikenellaceae family, which contains the Alistipes genus and has previously been linked to microbiomes from elderly people [22], was the most significantly overrepresented family within the middle and old groups in comparison to young mice when using 16S data (Kruskal-Wallis H test, Benjamini-Hochberg FDR multiple test correction p = 0.007) (Figure 3; Additional files 6 and 7). To ensure that this taxonomic link between frailer mice and people was not an artifact of using the 16S rRNA gene as a marker, an independent analysis using protein markers (PhyloSift) and phylogenetic placement (Pplacer) was conducted. The latter method has the advantage of identifying the phylogenetic context of sequenced reads but does not provide statistical significance testing. However, the results from this method did provide additional support that the Alistipes were more abundant within the old and middle mouse groups (Figure 4). The PhyloSift approach indicated that the old mice have lower abundances of organisms from the Lachnospiraceae family, a group often associated with the production of beneficial SCFAs [37], even though the 16S-based method did not show a significant difference (p = 0.7) between the age groups. This contrasting result suggests that the type of phylogenetic marker used for taxonomic assessment can give conflicting results for some taxon families. Lastly, the PhyloSift approach indicated that some members of the Bacteroidaceae family were abundant in the old and middle groups, while fewer were abundant in the young group, which did agree with the 16S results (old: 9.2% ± 7.9%; middle: 10.3% ± 1.3%; young: 3.9% ± 1.4%, p = 0.06).Figure 3

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