ABSTRACT
PIETER VAN DEN ABBEELE, WILLY VERSTRAETE, SAHAR EL AIDY, ANNELIES GEIRNAERT, AND TOM VAN DE WIELE
11.1 INTRODUCTION
Over the last decades, specific mechanisms of how the human gut microbiome determines human health or disease states have been elucidated (Round and Mazmanian, 2009). It has become clear that the dynamic interaction with these intestinal microbes can be divided in different stages over the human lifespan (Fig. 1). Drastic changes occur during the first years of life as the newborn gut progresses from a sterile environment to a densely populated microbial habitat. This gut ecosystem exerts restrictive selection on its microbial inhabitants as only microbes that are capable of establishing a mutualistic relation with the host are maintained (Backhed et al., 2005; Ley et al., 2008). In human infancy and early childhood, the complex microbial ecosystem is formed through the successive establishment of different bacterial groups; aerotolerant bacteria establish first,
followed by more and more strict anaerobes, as observed in ex-germfree reductionist animal models (Adlerberth and Wold, 2009). As a result, the infant gastrointestinal microbiota is quite variable in its composition and relatively unstable over time. On average, 3 years after birth the microbial community consists of a mixture of microbes that is largely similar to that found in the adult intestine (Yatsunenko et al., 2012). At that time, the complex microbiota is predominantly colonized by obligate anaerobes to provide a strong barrier against the establishment and proliferation of new bacterial groups, in a phenomena known as colonization resistance (Vollaard and Clasener, 1994). The colonizing microbes can rapidly shape themselves in response to changes in host environment. Likewise, when the host environment changes, the immune system and metabolic profile must adjust to these fluctuations in order to keep a mutualistic relationship with its microbiota. Although individual-specific and relatively stable in younger healthy adults, the microbiota in elderly displays greater interindividual variation (Claesson et al., 2011). Such high variation correlates with immunosenescence, which characterizes the ageing process (Claesson et al., 2012). Moreover, once its symbiotic coexistence is disrupted during acute (e.g. invasion of pathogens or antibiotic treatment) or chronic conditions (e.g. inflammatory bowel diseases and obesity), the microbial community may become a major threat to the host.
