Causal relationship between the composition of the Gut Microbiota and central precocious puberty: a two-sample Mendelian randomization study.

BACKGROUND

Previous observational research has demonstrated a possible association between the gut microbiota (GM) and central precocious puberty (CPP). Nevertheless, whether there is a causal relationship between the GM and CPP is uncertain due to the possibility of confounding factors influencing the result.

METHODS

We collected summary data from genome-wide association studies of the GM (MiBioGen, n = 18,340) and CPP (FinnGen Consortium, 185 case groups and 395,289 controls). Most of the participants were of European origin. Mendelian randomization analysis was utilized to investigate the causal relationship between the GM and CPP using the inverse-variance weighted average technique, the weighted median, and Mendelian randomization Egger. The reliability of the results was evaluated using the leave-one-out test and sensitivity analyses, including heterogeneity and horizontal pleiotropy testing.

RESULTS

According to the inverse-variance weighted average technique, there was a substantial correlation between CPP and the composition of the GM. Specifically, the relative abundance of the genus Bacteroides (OR 0.222, 95% CI 0.06-0.822, P = 0.024) and Alistipes (OR 0.197, 95% CI 0.056-0.697, P = 0.012), and others, showed significant associations. Furthermore, associations with the phylum Euryarchaeota, the orders Gastranaerophilales, and Rhodospirillales, the families Bacteroidaceae, and Desulfovibrionaceae were also observed. Sensitivity analyses and the leave-one-out test generated positive results for the genus Alistipes, implying that this genus is reliable and reduces the risk of CPP.

CONCLUSIONS

The composition of the GM may have a causal effect on CPP. The present finding that Alistipes may be protective against CPP is expected to offer novel insights into the management of CPP.