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. 2016 Jan 29;8(1):8.
doi: 10.1186/s13073-016-0262-7.

Signatures of early frailty in the gut microbiota

Matthew A Jackson, Ian B Jeffery  1 , Michelle Beaumont  2 , Jordana T Bell  3 , Andrew G Clark  4 , Ruth E Ley  5 , Paul W O'Toole  6 , Tim D Spector  7 , Claire J Steves  8
Affiliations

Signatures of early frailty in the gut microbiota

Matthew A Jackson et al. Genome Med. .

Erratum in

  • Erratum to: signatures of early frailty in the gut microbiota.
    Jackson MA, Jeffery IB, Beaumont M, Bell JT, Clark AG, Ley RE, O'Toole PW, Spector TD, Steves CJ. Jackson MA, et al. Genome Med. 2016 Feb 17;8(1):21. doi: 10.1186/s13073-016-0275-2. Genome Med. 2016. PMID: 26888550 Free PMC article. No abstract available.

Abstract

Background: Frailty is arguably the biggest problem associated with population ageing, and associates with gut microbiome composition in elderly and care-dependent individuals. Here we characterize frailty associations with the gut microbiota in a younger community dwelling population, to identify targets for intervention to encourage healthy ageing.

Method: We analysed 16S rRNA gene sequence data derived from faecal samples obtained from 728 female twins. Frailty was quantified using a frailty index (FI). Mixed effects models were used to identify associations with diversity, operational taxonomic units (OTUs) and taxa. OTU associations were replicated in the Eldermet cohort. Phenotypes were correlated with modules of OTUs collapsed by co-occurrence.

Results: Frailty negatively associated with alpha diversity of the gut microbiota. Models considering a number of covariates identified 637 OTUs associated with FI. Twenty-two OTU associations were significant independent of alpha diversity. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. A Faecalibacterium prausnitzii OTU was less abundant in frailer individuals, and retained significance in discordant twin analysis. Sixty OTU associations were replicated in the Eldermet cohort. OTU co-occurrence modules had mutually exclusive associations between frailty and alpha diversity.

Conclusions: There was a striking negative association between frailty and gut microbiota diversity, underpinned by specific taxonomic associations. Whether these relationships are causal or consequential is unknown. Nevertheless, they represent targets for diagnostic surveillance, or for intervention studies to improve vitality in ageing.

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Figures

Fig. 1
Fig. 1
OTU abundances significantly different between twin pairs discordant for frailty. Pairwise plots of abundance between twin pairs discordant for frailty are shown for OTUs that were significant at P <0.05 after Bonferonni adjustment considering both MZ and DZ pairs. Paired Wilcoxon rank-signed tests were used to compare abundances for the 22 significantly associated OTUs associated with FI after alpha adjustment. Three were significantly different; the Dorea OTU was significantly increased in frailer twins (P <10−4), whilst the F. prausnitzii and Lachnospiraceae OTUs were significantly lower (P = 0.001 and P <10−3, respectively). Note there are overlapping data points where multiple twins had zero counts (log abundance −6) for OTUs
Fig. 2
Fig. 2
Species abundance associates with FI. Shown are the unadjusted relative abundances versus FI for all species traits that were significantly associated with FI in mixed effects models, and had complete species name assignment. Below, similar plots for their parent genera. *Represents taxa whose association remained FDR significant after adjustment for alpha diversity. Q-values and coefficients shown are without alpha adjustment. Trends are highlighted by linear regression lines shown in red with 95 % confidence intervals shaded in grey. OTUs contained within these taxonomies retained significance within non-parametric analyses
Fig. 3
Fig. 3
Correlation of frailty, diversity and model covariates with modules of OTUs collapsed by co-occurrence. OTUs collapsed by co-occurrence into 21 modules labelled by colour (grey containing unassigned OTUs). The heatmap displays the correlation between the module eigenvector (ME, representing the combined module abundance as taken from the first PC of the module’s OTUs across all samples) and each variable. Modules and variables are hierarchically clustered using Euclidean distances. Student asymptotic P values for significant correlations (P <0.05) are shown. The most common taxonomic assignment within a module is shown next to its colour label
See this image and copyright information in PMC

References

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