Abstract

The microbiota of the aged is variously described as being more or less diverse than that of younger cohorts, but the comparison groups used and the definitions of the aged population differ between experiments. The differences are often described by null hypothesis statistical tests, which are notoriously irreproducible when dealing with large multivariate samples. We collected and examined the gut microbiota of a cross-sectional cohort of more than 1,000 very healthy Chinese individuals who spanned ages from 3 to over 100 years. The analysis of 16S rRNA gene sequencing results used a compositional data analysis paradigm coupled with measures of effect size, where ordination, differential abundance, and correlation can be explored and analyzed in a unified and reproducible framework. Our analysis showed several surprising results compared to other cohorts. First, the overall microbiota composition of the healthy aged group was similar to that of people decades younger. Second, the major differences between groups in the gut microbiota profiles were found before age 20. Third, the gut microbiota differed little between individuals from the ages of 30 to >100. Fourth, the gut microbiota of males appeared to be more variable than that of females. Taken together, the present findings suggest that the microbiota of the healthy aged in this cross-sectional study differ little from that of the healthy young in the same population, although the minor variations that do exist depend upon the comparison cohort. IMPORTANCE We report the large-scale use of compositional data analysis to establish a baseline microbiota composition in an extremely healthy cohort of the Chinese population. This baseline will serve for comparison for future cohorts with chronic or acute disease. In addition to the expected difference in the microbiota of children and adults, we found that the microbiota of the elderly in this population was similar in almost all respects to that of healthy people in the same population who are scores of years younger. We speculate that this similarity is a consequence of an active healthy lifestyle and diet, although cause and effect cannot be ascribed in this (or any other) cross-sectional design. One surprising result was that the gut microbiota of persons in their 20s was distinct from those of other age cohorts, and this result was replicated, suggesting that it is a reproducible finding and distinct from those of other populations.

Highlights

  • The microbiota of the aged is variously described as being more or less diverse than that of younger cohorts, but the comparison groups used and the definitions of the aged population differ between experiments

  • The recent consensus is that, in aggregate, the diversity of the gut microbiota declines with age [10], whether this is associated with healthy aging is controversial and the delineation of what is normal in different cohorts are still not clear

  • While our cross-sectional cohort precludes the assignment of cause and effect, our results suggest that diet and lifestyle choices consistent with healthy aging even into the 10th decade of life include a healthy and diverse microbiota

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Summary

Introduction

The microbiota of the aged is variously described as being more or less diverse than that of younger cohorts, but the comparison groups used and the definitions of the aged population differ between experiments. IMPORTANCE We report the large-scale use of compositional data analysis to establish a baseline microbiota composition in an extremely healthy cohort of the Chinese population. The search for healthy aging has been resurrected by the ability to identify a plethora of microbes at various body sites, the gut, and to show that they influence and are influenced by health there and at distant sites [2, 3] This has led to investigations into the development of the gut microbiota throughout life, with some studies reporting a gradual change over time [4] based upon relatively small sample sizes [5,6,7]. We gained access to a large number of fecal samples from a variety of communities across the age continuum in China and used a compositionally coherent approach to examine the variance of the OTUs across all samples with age as a continuous variable for exploratory data analysis and compositional association and as a discrete variable for differential abundance analysis

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