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

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://clinicaltrials.gov/show/NCT00298337. The adult-comparison cohort (HELMi) is NCT03996304.

Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome but Affects Amino Acid Metabolism in Sera of Obese Girls With Polycystic Ovary Syndrome

“…Others have posited a role of Ruminococcacea in the regulation of bioavailable sexhormones. (Korpela et al, 2021) These studies suggest that Ruminococcacea is involved in the metabolic and hormonal interplay in obesity and PCOS but it is specific role and contribution in the pathophysiologic mechanism is an area for further investigation.…”

“…( Eyupoglu et al, 2019 ) Recent studies also suggest exogenous hormone treatment of PCOS may involve gut microbiome-host interactions. Shifts in the gut microbial communities occur in girls during puberty aligning more closely to adult microbiome profiles, particularly in the relative distribution of estrogen-metabolizing microbial communities ( Korpela et al, 2021 ). Inverse shifts in the relative abundance of gut microbial communities have also been demonstrated in women post-menopause, which lends credence to the notion that sex-hormones may underlie shifts in the gut microbiome.…”

Spotlight on the Gut Microbiome in Menopause: Current Insights

“… 16 , 17 A shift towards sexual dimorphism of the gut microbiome may occur during puberty and adolescence, since teenage male-female dizygotic twin pairs have greater microbiome dissimilarity than same gendered dizygotic twin pairs, a pattern not observed in infancy, 18 and the gut microbiome in girls was shown to shift toward an adult-like state during pubertal progression. 19 Post-pubertal sexual dimorphism of the gut microbiome is supported by animal studies: weanling male and female mice are indistinguishable in their gut microbiome composition, but sex differences emerge at puberty and are most apparent in adult mice. 20 , 21 This evidence strongly implicates sex hormones in shaping gut microbiome structure during puberty and onward.…”

Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial

“…Fecal DNA is extracted by repeated bead beating from ca. 125 mg of fecal material [33] and processed for sequencing of the hypervariable V3-V4 region of the 16S rRNA gene using primers 341F 5′-CCT ACG GGNGGC WGC AG-3′ and 785R 5'-GAC TAC HVGGG TAT CTA ATC C-3′ [15,34] and barcoding primers from Kozich et al [35] as explained in detail elsewhere [36]. The pooled libraries are sequenced with Illumina MiSeq platform using a MiSeq v3 reagent kit (MS-102-3003) with 5% PhiX as spike-in (Illumina).…”