Introduction: The human fecal microbiota is known to shift in composition during adolescence, but whether fecal microbiota is associated with timing of sexual maturation is unknown. In mice, the change in the composition of fecal microbiota during puberty appears to be sex-specific and associate with changes in testosterone. We investigated the association between intestinal microbiota and pubertal timing in adolescents.
Subjects and Methods: The study is an allergy-prevention-trial cohort including 415 participants with high risk for allergy. The subjects randomly received a mixture of four probiotics with prebiotic, or placebo, for the first six months of life. The treatment did not affect growth.
At the 13-year-follow-up, participants provided a fecal sample, and their growth data were analysed. Microbiota composition of the fecal samples was analysed by 16S rRNA amplicon sequencing. Samples with less than 900 reads were excluded.
We modelled height progression with a polynomial function and produced individual growth velocity curves for each participant. We identified age at peak height velocity (APHV), a marker of puberty timing, using the derivative of the growth velocity curve. We calculated time from peak height velocity (TPHV), a marker of pubertal maturation by subtracting age at fecal sampling from age at peak height velocity. We used P<0.001 as a cut-off point, and limited the analysis on bacterial genera. The statistical analysis was carried out with R using the mare-package. The analysis was adjusted for relevant confounders.
Results: Sufficient growth data for assessment of puberty timing was available from 35% of the 415 participants (60% females, 40% males). One girl and 16 boys were prepubertal (self-reported Tanner staging). Among boys, TPHV was negatively correlated with relative abundance of Burkholderia (β = -1.549). Ignoring the samples with zero-observations, TPHV was negatively correlated with the abundance of Actinomyces (β = -1.091). Among girls, TPHV was positively correlated with the abundance of Gemella (β = 0.573) and negatively with Barnesiella (β = -0.145) and Oscillospira (β = -0.493). Ignoring samples with the zero-observations, TPHV was also positively correlated with the abundance of Anaerospora (β = 0.350) and Solobacterium (β = 0.337) and negatively with the abundance of Megamonas (β = -1.789).
Results for APHV were very similar to those with TPHV.
Conclusion: We conclude that the timing of human puberty is correlated with fecal microbiome in a sex-specific manner.
Raivio and Kuitunen contributed equally to this work.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology