Abstract

The intestinal microbiome plays a central role in human health and disease. While its composition is relatively stable throughout adulthood, the microbial balance starts to decrease in later life stages. Thus, in order to maintain a good quality of life, including the prevention of age-associated diseases in the elderly, it is important to understand the dynamics of the intestinal microbiome. In this study, stool samples of 278 participants were sequenced by whole metagenome shotgun sequencing and their taxonomic and functional profiles characterized. The two age groups, below65 and above65, could be separated based on taxonomic and associated functional features using Multivariate Association of Linear Models. In a second approach, through machine learning, biomarkers connecting the intestinal microbiome with age were identified. These results reflect the importance to select age-matched study groups for unbiased metagenomic data analysis and the possibility to generate robust data by applying independent algorithms for data analysis. Furthermore, since the intestinal microbiome can be modulated by antibiotics and probiotics, the data of this study may have implications on preventive strategies of age-associated degradation processes and diseases by microbiome-altering interventions.

Highlights

  • Genetic diversity between humans does arise from allele frequency differences of shared human genes, and from the vast number of genetic and metabolic diversity in intestinal microbial communities

  • 23 ± 9.9 (SD) million non-human high-quality reads per sample remained for further processing

  • Both approaches showed that the class Betaproteobacteria as well as its order Burkholderiales and the family Sutterellaceae including the species Suturella wadsworthensis had a higher relative abundance in the below65 age group, whereas the class Gammaproteobacteria and its family Enterobacteriaceae had a higher relative abundance in the above65 age group compared to the respective other group

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Summary

Introduction

Genetic diversity between humans does arise from allele frequency differences of shared human genes, and from the vast number of genetic and metabolic diversity in intestinal microbial communities. The human intestinal microbiome is a complex system consisting of trillions of microorganisms that contribute to numerous functions of the host. Fermentation of indigestible food components, stimulation and regulation of the immune system, strengthening of the intestinal barrier and protection against pathogens [1] are some of the key functions of the intestinal microbiome. Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique Federale de Lausanne), Lausanne, Switzerland (CF10000044 – EPFL SCR0237812), https://www. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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