Differential Alterations of Gut Microbiota in Girls with Isolated Obesity, Isolated Precocious Puberty, and Their Comorbidity

Abstract Background Childhood obesity and precocious puberty (PP) are escalating public health concerns with a significant comorbidity. Emerging evidence implicates gut microbiota dysbiosis in both conditions, yet microbial associations with their co-occurrence remain unexplored. Methods A total of 68 girls (18 normal, 25 PP-only, 18 obesity-only, and 7 obesity-PP comorbidity) were enrolled. 16S rRNA sequencing was applied to determine gut microbiota of girls. Microbial diversity, composition, and differential abundant taxa were analyzed. Results While overall microbial diversity and community structure were similar across groups, obesity-only subjects exhibited significantly increased microbial richness (Chao1 index, P<0.01 vs. all groups), characterized by a higher Firmicutes/Bacteroidota ratio (P<0.001 vs. normal/PP), increased Proteobacteria (P<0.001 vs. normal), and enrichment of genera including Blautia, Faecalibacterium, Roseburia, Anaerostipes, Haemophilus, and Lachnospiraceae_NK4A136_group (P<0.05 vs. other groups). PP-only subjects showed reduced Verrucomicrobiota (P<0.001 vs. normal/obesity) and elevated Escherichia_Shigella (P<0.05 vs. normal). Most strikingly, the obesity-PP comorbid group exhibited a unique gut microbiota profile characterized by a dramatic depletion of Firmicutes compared to the obesity-only group (P<0.001) and a remarkable nearly 100-fold increase in Verrucomicrobiota abundance (P<0.001 vs. other groups), suggesting a distinct microbial ecotype potentially contributing to the pathophysiology of this comorbidity. Conclusion This study delineated unique gut microbiota alterations associated with isolated obesity, isolated PP, and their comorbidity in girls. The distinct dysbiotic pattern in comorbid obesity-PP suggested complex microbiota-host interactions, providing a new microbiological perspective for understanding the mechanism of comorbidity between obesity and precocious puberty.