Network analysis of OTUs in boys resulted in 2 clearly distinct clusters of co-occurring bacteria, which showed a striking association with body composition (Fig. 2). One “fat” cluster represented OTUs associated with FMI z score, whereas the second “lean” cluster represented OTUs associated with FFMI and BMI z scores. One OTU (Greengenes ID: 591285) identified as Bifidobacterium longum was located between both clusters and correlated with both FMI and BMI z scores. In accordance with our Adonis and NMDS results, these same OTUs did not show any clustering by sex (Supplemental Figure 2, Supplemental Digital Content 4, http://links.lww.com/MPG/B216) or body composition for girls (Supplemental Figure 3, Supplemental Digital Content 5, http://links.lww.com/MPG/B217).
In summary, our results suggest that there is a sex-specific relationship between the faecal microbiota of 2- to 3-year-old well-nourished children and their body composition. Our initial analysis suggested that the fecal microbiota profiles of the entire cohort were significantly associated with FFMI and BMI z scores, but stratifying these data with respect to sex suggested these gross associations were principally driven by a male-specific association between fecal microbiota profile and FFMI z score. Moreover, our network analysis in boys further identified 2 specific clusters of bacteria that appear to be linked with either FFMI or FMI z scores. Further support for a sex-specific association between microbiota composition and growth is provided by reports of antibiotic exposure in early life being associated with increased childhood BMI in boys but not girls (37,38). In addition, treatment of mice with low-dose penicillin has been reported to increase weight and lean mass in male, but not female mice (39).
Sex-based differences in the gut microbiota have been reported in adults, with men shown to have significantly higher abundance of F prausnitzii compared to women (40). Among our cohort of young children, microbiota profiles were, however, not found to significantly differ by sex. Sexual dimorphism in body composition was seen in our cohort, with BMI z score associated with FFMI z score in boys and FMI z score in girls. Although FFMI and BMI z scores were not significantly different by sex, FMI z score was found to vary by sex with girls in our cohort having a higher mean FMI z score compared to boys. This could be a reflection of a limitation of this study in that fat-free mass and fat mass were estimated using the deuterium oxide dilution technique, whereas NHANES skinfold thickness data were used as the reference to create z scores, due to the lack of alternative more appropriate body composition references for 2- to 5-year-old children (20).
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