Gut microbiota develop towards an adult profile in a sex-specific manner during puberty

Katri Korpela, Sampo Kallio, Anne Salonen, Matti Hero, Anna Kaarina Kukkonen, Päivi J Miettinen, Erkki Savilahti, Ella Kohva, Laura Kariola, Maria Suutela, Annika Tarkkanen, Willem M de Vos, Taneli Raivio, Mikael Kuitunen, Katri Korpela, Sampo Kallio, Anne Salonen, Matti Hero, Anna Kaarina Kukkonen, Päivi J Miettinen, Erkki Savilahti, Ella Kohva, Laura Kariola, Maria Suutela, Annika Tarkkanen, Willem M de Vos, Taneli Raivio, Mikael Kuitunen

Abstract

Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006-Retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT00298337 . The adult-comparison cohort (HELMi) is NCT03996304.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Figure 1
Figure 1
(a) Microbiota similarity to that in adults in relation to pubertal timing (time to/from peak growth velocity) in girls. (b) Microbiota similarity to that in adults in relation to pubertal timing (time to/from peak growth velocity) in boys.
Figure 2
Figure 2
(a) Principal coordinates analysis of gut microbiota composition in girls compared with adults of the same sex. (b) Principal coordinates analysis of gut microbiota composition in boys compared with adults of the same sex.
Figure 3
Figure 3
(a) Abundance of Clostridiales in relation to pubertal timing (time to/from peak growth velocity) in girls. (b) Abundance of Bacteroidales in relation to pubertal timing (time to/from peak growth velocity) in girls. (c) Bacteroidales/Clostridiales ratio in relation to pubertal timing (time to/from peak growth velocity) in girls. (d) Abundance of Clostridiales in relation to pubertal timing (time to/from peak growth velocity) in boys. (e) Abundance of Bacteroidales in relation to pubertal timing (time to/from peak growth velocity) in boys. (f) Bacteroidales/Clostridiales ratio in relation to pubertal timing (time to/from peak growth velocity) in boys.
Figure 4
Figure 4
(a) Association between exposure to cephalosporin and pubertal timing (time to/from peak growth velocity) in girls. (b) Association between exposure to cephalosporin and pubertal timing (time to/from peak growth velocity) in boys. (c) Association between exposure to macrolide, and pubertal timing (time to/from peak growth velocity) in girls. (d) Association between exposure to macrolide, and pubertal timing (time to/from peak growth velocity) in boys.
Figure 5
Figure 5
(a) Multivariate model for pubertal timing in girls. (b) Multivariate model for pubertal timing in boys.

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