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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).  Age-related spatio-temporal variations in the microbiota are best viewed within an ecological- evolutionary framework (see review by Costello et al., 2012). Diet is a major, controllable environmental factor influencing the composition of the host microbiome, with the high-fat, sugar-rich Western diet contributing to a Bacteroides-dominant microbiome and high-fiber diet to one dominated by Firmicutes with a strong correlation between long-term diet and enterotypes (Wu et al., 2011). In terms of ecological succession, the Bifidobacterium-dominated microbiota of the infant changes over time into the Bacteroidetes- and Firmicutes-dominated microbiota of the adult (Ottman et al., 2012), remaining fairly stable through adulthood in the absence of perturbations like long-term dietary changes or repeated antibiotic intervention. Pathogens may then be viewed as invasive species in the ecological sense, constantly testing the resilience of the native ecosystem, resulting in their elimination, low-level persistence (enabling future opportunism), or establishment causing disease.

Aging and the human gut microbiotaâ€”from correlation to causality