Genes Nutr (2011) 6:209–240 The microbial composition at different stages of life and its relation to health The intestinal microbiota of healthy adult individuals is relatively stable over time (Costello et al. 2009; Franks et al. 1998; Vanhoutte et al. 2004; Zoetendal et al. 1998). However, intra-individual ﬂuctuations occur due to envi- ronmental changes and pathological events. In addition, substantial changes in the composition of intestinal microbiota occur at both ends of life, in infants and elderly individuals (Tiihonen et al. 2010; Vael and Desager 2009). Since alterations in the microbial composition are recog- nised to be of inﬂuence on human health, the interest in the development and composition of the microbiota of infant and elderly humans has signiﬁcantly increased in the last years. It is widely accepted that microbial colonisation of the GI tract starts during and directly after birth when neonates are exposed to bacteria that are derived from the mother and the surrounding environment (Adlerberth and Wold 2009; Mackie et al. 1999). Yet, the human foetal environment is not completely microbiologically sterile and there are indications that non-pathological in utero exposure of the foetus to intestinal bacteria or bacterial DNA frequently occurs (Pettker et al. 2007; Satokari et al. 2009). In addition, the isolation of bacteria from the meconium (the ﬁrst stool of the neonate), umbilical cord blood and amniotic ﬂuid of healthy neonates has been reported (Jime´nez et al. 2005, 2008). Postnatal colonisation of the GI tract is highly var- iable amongst neonates and is inﬂuenced by several factors including mode of delivery, type of infant feeding, gesta- tional age, infant hospitalisation and antibiotic use (Penders et al. 2006). It is, however, still unclear how each of these factors exactly inﬂuences the infant microbial diversity and how this is related to health. A disturbed development of the infant microbiota has been associated with the development of disease later in life (Vael and Desager 2009). For example, associations have been made between dysbiosis in infants and the later development of childhood obesity (Collado et al. 2008b; Kallioma¨ki et al. 2008) and atopic and allergic diseases (Bjo¨ rkste´n et al. 2001; Kallioma¨ki et al. 2001; Penders et al. 2007; Sjo¨ gren et al. 2009; Wang et al. 2008). Several culture-independent studies have shown that there is a large inter-individual variability amongst infants in the development of the microbiota (Favier et al. 2002; Palmer et al. 2007; Penders et al. 2006; Roger et al. 2010). In addition, it has been demonstrated that the infant microbiota is highly dynamic and develops in a step-wise fashion with an increase in diversity over time (Palmer et al. 2007; Roger et al. 2010). An important stage in the colonisation of the GI tract of infants is the period in which the infants feed on the milk they receive either by 215 breastfeeding or by infant-formula feeding. During this period, the faecal microbiota of infants consists mainly of biﬁdobacteria (Roger and McCartney 2010; Roger et al. 2010). Some biﬁdobacteria are highly adapted to the digestion of the oligosaccharides present in human milk (Zivkovic et al. 2010). The infant intestinal microbiota contains a relatively low diversity in Biﬁdobacterium populations; B. breve, B. biﬁdum and B. longum subsp. infantis are the most common Biﬁdobacterium species (Roger et al. 2010). Compared with breast-fed infants, the intestinal microbiota of formula-fed infants is characterised by less diverse Biﬁdobacterium populations (Roger et al. 2010) and more complex communities of Clostridia, Enterobacteriaceae, Bacteroides and Enterococcus (Harmsen et al. 2000; Penders et al. 2006). The introduc- tion of solid food (weaning) marks an increase in microbial diversity and changes in the microbial composition towards an adult microbiota (Koenig et al. 2010). For example, dominant Biﬁdobacterium populations change; B. adole- scentis, B. catenulatum and B. longum subsp. longum are more abundantly present in the adult microbiota (Matsuki et al. 2004). The successive shifts of different microbial communities within the ﬁrst years of life ultimately result in the development of an adult-like microbiota. In the elderly (usually deﬁned as people over the age of 65), there are major physiological changes that have an impact on the composition and the functionality of the intestinal microbiota (Tiihonen et al. 2010; Woodmansey 2007). Many elderly humans suffer from decreased intes- tinal motility, which can result in prolonged intestinal transit time and faecal retention. Age-related changes, such as decreased senses for smell and taste, dental decay and swallowing difﬁculties can lead to narrowing of the nutritional intake and even malnutrition. In addition, the age-related gradual deterioration of the immune system (immunosenescence) is associated with changes in intesti- nal microbiota composition (Schiffrin et al. 2010). Furthermore, the increased use of laxatives, antibiotics and other medication in elderly individuals will affect intestinal microbiota composition. Culture-independent studies have demonstrated that the composition of the intestinal microbiota signiﬁcantly changes with age (Bartosch et al. 2004; Mariat et al. 2009; Mueller et al. 2006; Zwielehner et al. 2009). Recently, high-throughput methods have been applied to study the changes in the intestinal microbiota of elderly individuals. Biagi and colleagues have used the HITChip, a phylo- genetic microarray speciﬁcally designed to study the human GI tract microbiota, to compare the intestinal microbiota composition of young adults with that of elderly indivi- duals and centenarians. It was demonstrated that especially the microbiota of centenarians showed signiﬁcant differ- ences compared with microbiota composition of the other 123