Aging and the human gut microbiota—from correlation to causality

The human gastrointestinal (GI) tract harbors the largest number and concentration of microbes found in the human body. Perturbations in the gut microbial ecosystem have also been associated with conditions as diverse as chronic GI diseases (e.g., Crohn's disease, ulcerative colitis), metabolic disorders (e.g., diabetes types 1 and 2, obesity) and antibiotic use (for a review see Sekirov et al., 2010). Metagenomic culture-independent methods have enabled the unraveling of the complexity of the gut microbiota (Rajilic-Stojanovic et al., 2009). Given the considerable inter-individual diversity in the actual composition of the microbiota, significant collaborative attempts have been made to systematize the available knowledge (Arumugam et al., 2011; Human Microbiome Project Consortium, 2012) and identify “core” microbiota that are conserved among humans to facilitate meaningful comparisons (Huse et al., 2012). Changes in the microbial composition also take place with age, with a high degree of variability at the two extremes of infancy and old age, punctuated by comparative stability during adulthood (for reviews, see Woodmansey, 2007; O'Toole and Claesson, 2010). Given that increases in life expectancy will likely result in an increase in the elderly population worldwide, analysis of the contribution of the microbiota to healthy aging assumes greater significance (for a recent review, see Tiihonen et al., 2010).