Genes Nutr (2011) 6:209–240 Modulation of the intestinal microbiota Since it is known that the intestinal microbiota plays an important role in human health and disease, manipulation of these microorganisms by antibiotics, probiotics, pre- biotics and synbiotics are attractive approaches to improve and maintain health (Gareau et al. 2010; Preidis and Versalovic 2009). Antibiotics are widely used as antimicrobial agents to treat bacterial infections caused by pathogenic micro- organisms. In general, however, antibiotics (even narrow- spectrum antibiotics) do not only affect pathogens, but also commensal intestinal microbial communities. This can result in dysbiosis of the intestinal microbiota, subse- quently leading to intestinal problems, such as antibiotic- associated diarrhoea (AAD) (McFarland 1998). The anti- biotic-induced disturbances in microbiota composition can be temporary, returning to its original composition within 2 months, but recently also medium and long-term distur- bances in (speciﬁc) microbial communities have been described (Dethlefsen et al. 2008; Jernberg et al. 2007, 2010; Koning et al. 2010). An additional problem of the widespread antibiotic use, is the increased prevalence of antibiotic resistance resulting from the transfer of antibiotic resistance genes amongst microorganisms (Jernberg et al. 2010). The intestinal microbiota can be modulated in a more biological manner by the use of probiotics. According to the deﬁnition formulated by the World Health Organisation (WHO) probiotics are ‘live microorganisms which, when administered in adequate amounts, confer a health beneﬁt on the host’ (FAO/WHO 2002). Moreover, prebiotics are used to manipulate the microbiota composition in the GI tract. The deﬁnition of prebiotics is even more generic than the one of probiotics: ‘non-digestible food ingredients that, when consumed in sufﬁcient amounts, selectively stimulate the growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health beneﬁts to the host’ (Roberfroid et al. 2010). Mixtures of both probiotics and prebiotics are referred to as synbiotics. The ﬁnal part of this review will focus on probiotics as a way to modulate the intestinal microbiota. The opportuni- ties for probiotic intervention in maintaining and restoring health are increasingly being acknowledged, and the ﬁeld of probiotic research has grown signiﬁcantly during the past few years (Gareau et al. 2010; Ng et al. 2009; Rijkers et al. 2010). An introduction to probiotics In line with the very generic deﬁnition of probiotics, many different microorganisms have been studied for their 227 potential use as a probiotic, in relation with a wide range of biological or clinical effects. Most of the microorganisms that have been studied are naturally present in the human GI tract. At this moment, the most commonly used pro- biotic microorganisms belong mainly to the bacterial genera Lactobacillus and Biﬁdobacterium (Boesten and De Vos 2008; Kleerebezem and Vaughan 2009). These two genera contain a large number of species and strains of which many are being used as probiotic strains. In addition to these genera, the probiotic market contains members from some additional lactic acid bacterial genera, such as Streptococcus and Enterococcus, and members from the genera Bacillus and Propionibacterium. Furthermore, some gram-negative bacteria (e.g. E. coli Nissle 1917) and yeast (e.g. Saccharomyces) are being used as probiotic micro- organisms (Gareau et al. 2010; Holzapfel et al. 1998; Iannitti and Palmieri 2010). Numerous health-beneﬁcial effects have been attributed to probiotic microorganisms (Iannitti and Palmieri 2010; Ng et al. 2009). In general, these health beneﬁts can be categorised into three levels of probiotic action (Rijkers et al. 2010). First of all, probiotic microorganisms can act directly within the GI tract (level 1), for example by direct interaction with the intestinal microbiota or by enzymatic activities. Secondly, they can interact directly with the intestinal mucus layer and epithelium (level 2), thereby inﬂuencing the intestinal barrier function and the mucosal immune system. Thirdly, probiotics can have effects out- side the GI tract (level 3), for example on the systemic immune system and other organs, such as the liver and the brain. Although in vivo data are emerging, most of the mechanistic studies with probiotic microorganisms have been performed in vitro, ex vivo or with the aid of animal models. The in vitro activity of a given probiotic does not necessarily correlate with the efﬁcacy of the intended clinical in vivo. In addition, it is important to note that each probiotic strain has its own speciﬁc properties. The health beneﬁts that can be attributed to one probiotic strain cannot be extrapolated to other probiotic strains or mixtures of strains. Even closely related microbial strains of the same species may have different physiological effects (Medina et al. 2007; Meijerink et al. 2010; Lo´pez et al. 2010; Snel et al. 2010; Van Hemert et al. 2010; Vissers et al. 2010, 2011). Nowadays, multistrain or multispecies probiotic mix- tures, which contain more than one probiotic strain, are becoming increasingly popular (Chapman et al. 2011; Timmerman et al. 2004). Compared with single strain probiotics, probiotic mixtures have the possible advantage that the properties of single strains may have additive or even synergistic effects when put in a mixture together with other probiotics strains, which can result in higher efﬁcacy. Another potential advantage of probiotic mixtures 123