Genes Nutr (2011) 6:209–240 maintenance and severity is possible and will have to be explored in the future. Microbial diversity and obesity Obesity is a complex disease characterised by excess body fat accumulation. It has been associated with phylum-level changes in the composition of the intestinal microbiota (Table 4). An increase in the relative abundance of Firmi- cutes and a reduction in the level of Bacteroidetes has been observed in both obese mice (ob/ob) (Ley et al. 2005) and humans (Ley et al. 2006). However, since the original publication, a series of studies have failed to conﬁrm the study of Ley and colleagues and shown variable results with respect to the compositional changes in the microbiota of obese humans (Collado et al. 2008b; Duncan et al. 2008; Kallioma¨ki et al. 2008; Nadal et al. 2009; Santacruz et al. 2009, 2010; Schwiertz et al. 2010; Zhang et al. 2009). Altogether these data suggest that instead of phylum-level changes, more subtle changes in the composition of the intestinal microbiota are associated with the development of obesity. Recently, Turnbaugh and colleagues have observed a reduced compositional microbial diversity in obese indi- viduals compared with lean individuals (Turnbaugh et al. 2009). It is evident that (excessive) food intake has an inﬂuence on body (over)weight. Recently, a direct link between intestinal microbiota composition and body weight has been suggested. One of the ﬁrst publications that provides evidence for this link is the publication by Ba¨ckhed and colleagues for which they colonised germ-free mice with the microbiota of conventionally raised mice (Ba¨ckhed et al. 2004). They observed an increase of body fat content of the colonised germ-free mice despite reduced food intake, which was suggested to be caused by the intro- duction of intestinal microbial communities. In a later study, it was demonstrated that the absence of intestinal microorganisms protected germ-free mice against the development of obesity after being fed a high-fat, sugar- rich diet (Ba¨ckhed et al. 2007). Furthermore, it was demonstrated that colonisation of germ-free mice with the microbiota of obese mice induced a signiﬁcant greater increase in body fat weight compared with germ-free mice colonised with the microbiota of lean mice (Turnbaugh et al. 2006). In addition, these experiments in germ-free mice have demonstrated that the intestinal microbiota is involved in the regulation of fat storage. It was shown that introduction of an intestinal microbiota resulted in an increase in metabolic rate, modulation of de novo lipo- genesis and an increase in the uptake of monosaccharides from the intestine (Ba¨ckhed et al. 2004). Based on these results, it has been hypothesised that obese individuals are more efﬁcient in converting food into usable energy and in 221 storing this energy in fat than lean individuals (Turnbaugh et al. 2006). As discussed above, the intestinal microbiota has a crucial role in the digestion of food, in particular the metabolism of polysaccharides and oligosaccharides and the production of SCFA that provide the host with addi- tional amounts of energy. Altered representation of bacte- rial genes and metabolic pathways, including those involved in nutrient harvest, were found to be related to obesity (Turnbaugh et al. 2009). The results from this study demonstrate that major insights in the differences between various physiological states of the host (in this case obese vs. lean) can be obtained by studying the functional microbial diversity in addition to phylogenetic diversity. In line with this conclusion is the observation that the amount of SCFA produced by the intestinal microbiota rather than the changes in the composition of the microbiota are important in the development of obesity (Schwiertz et al. 2010). As for IBD and IBS, which were discussed above, also for obesity the question remains whether dysbiosis of the intestinal microbiota is a direct cause for obesity or whe- ther it reﬂects a disturbed host environment. It needs to be established whether the changes in the intestinal microbial communities in obese individuals are not merely an adap- tation to a change in the host’s diet. Some of the studies that have shown an altered composition of the intestinal microbiota in obese individuals, have also incorporated analysis of the effect of diet change on the observed dys- biosis (Table 4) (Duncan et al. 2007, 2008; Ley et al. 2006; Nadal et al. 2009; Santacruz et al. 2009). Little is known, however, about the inﬂuence of dietary change on micro- biota composition in humans. A recent study demonstrated rapid and reversible changes in the relative abundance of speciﬁc dominant bacterial groups after dietary changes (Walker et al. 2011a). Most striking was the strong increase in the relative abundance of Ruminococcus bromii and Eubacterium rectale phylotypes as result of a diet rich in resistant starch. It was suggested that indigestible dietary polysaccharides can substantially change the composition of the intestinal microbiota, however, it is likely that this depends on the initial composition of the intestinal microbiota. Interestingly, R. bromii and E. rectale were identiﬁed as key degraders of starch in an in vitro model of the human colon, using 16S rRNA-based stable isotope probing (Kovatcheva–Datchary et al. 2009). Recent studies in mice show that the inﬂuence of the diet (high-fat vs. standard chow or low-fat) on the composition of the intestinal microbiota is independent of genetic disposition for obesity (Hildebrandt et al. 2009; Murphy et al. 2010). In addition to obesity, it has also been suggested that the intestinal microbiota is involved in obesity-associated metabolic disorders, such as type 2 diabetes metabolic endotoxemia, low-grade inﬂammation and adiposity (Cani 123