Cindy Boer

The Gut Microbiome of Childen and Adults | 219 5.1 our cohorts replicated the previously reported negative association between α-diversity and BMI[40]. Additionally, BMI was also associated with community composition (Bray- Curtis) in both RS and GenR cohorts, as reported for the LLD and FGFP cohorts. Also, Alistipes and Barnesiella were reported as negatively associated with BMI in all four of these cohorts. Interestingly, the lower Firmicutes abundance observed in the GenR and COPSAC children cohorts compared to RS, LLD and FGFP adult cohorts suggests an age- specific phenomenon is responsible for this difference. However, understanding these differences merit further investigation. Thus, as both our RS and GenR datasets contain many characteristics that are similar to previously published large cohort studies, we conclude that our datasets allow valid investigations into the composition and variation of the gut microbiota across child and adult subjects. Comparing the gut microbiome composition between children and adults in a combined dataset of 3,083 children and adults showed significant clustering of the cohorts based on overall composition (PCoA beta diversity) and significant different α-diversities. The lower diversity in GenR suggested a lack of ‘maturation’ of the gut microbiome in children. However, we did not observe a significant age-related change in alpha diversitywithin each cohort separately. This might be due to the narrow age-range in both cohorts (9.8±0.32 in GenR, 56.8±5.9 in RS, Table 2 ). At genus level, the relative abundances of genus Bacteroides were higher in GenR than in RS. Members of the genus Bacteroides are specialized at utilizing both plant and host-derived polysaccharides[49-52]. As compared to other genera, Bacteroides have a large number of genes special- ized to metabolize various glycans. They also have environmental sensors that control their expression upon exposure to glycans. The predicted metagenomics data showed indeed higher abundances of glycan degradation pathways in children’s gut microbi- ome than in adults. In contrast, the relative abundances of the genus Blautia were high- er in RS than in GenR. Blautia digest complex carbohydrates like whole-grains[53] and its abundance has been shown to be reduced in patients with colorectal cancer[54] and in children with type 1 diabetes[55]. Its abundance has also been reported to be in- versely related to bone mineral density in human[56]. In fact, the relative abundance of Blautia and Bacteroides, has been implicated as a determinant of the so-called ‘healthy microbiome’ due to differences in the metabolic functions of these genera[54,55,57,58]. With respect to metabolic functions, we identified many predicted carbohydrate pathways that were significantly enriched in adult versus child metagenome datasets, with many of these carbohydrate pathways involving the metabolism of simple sug- ars such as fructose and mannose. However, whether these differences in microbiota profiles can be explained by possible differences in energy demand and metabolic pro- gramming between adults and children remains to be proven. Other interesting differ-