Objective Central precocious puberty (CPP) is a common pediatric endocrine disorder and a significant global public health concern. Emerging evidence suggests an association between bile acids (BAs) and CPP, although their regulatory roles and underlying mechanisms remain poorly understood. Methods We conducted untargeted metabolomics and targeted BA analysis on serum samples from female rats with high-fat diet-induced CPP to identify metabolites potentially involved in regulating puberty through modulation of Sirt1 and Kiss1 expression in the hypothalamus. Identified BAs were then administered via gavage to female rats with CPP to assess their effects. To explore the mechanisms by which these BAs affect the development of CPP, gut microbiota and their metabolites were analyzed using 16S rRNA sequencing and untargeted metabolomics. Results Our findings revealed significant reductions in glycodeoxycholic acid (GDCA) and glycoursodeoxycholic acid (GUDCA) levels in female rats with CPP. GDCA treatment delayed the onset of puberty, accompanied by alterations in the gut microbiota functions and metabolic pathways related to oxidative stress (OS) and fatty acid metabolism. Mediation analysis suggested that OS-related metabolites, including gamma-glutamylcysteine and malonic acid, which increased with the abundance of Lachnospiraceae UCG-001, facilitated the reduction of Sirt1 expression. Additionally, pregnenolone appeared to suppress the beneficial effect of Parasutterella in enhancing Sirt1 expression. Conclusion This study demonstrates that GDCA exhibits a potential therapeutic effect on CPP through a unique mechanism that involves gut microbiota modulation, alterations in serum metabolites, and changes in the expression of key regulatory factors Sirt1.

Precocious puberty (PP) is the second most common pediatric endocrine disorder globally and poses a growing public health concern, particularly among girls. While the exact biological mechanisms underlying PP remain unclear, unhealthy dietary patterns, particularly the consumption of a high-fat diet (HFD), are recognized as significant modifiable risk factors. The gut microbiota (GM) is an environmental factor that is disrupted by HFD and may modulate the onset and progression of PP. This review explored the intricate relationship between HFD, GM, and PP, and elucidated the potential mechanisms by which HFD may promote PP development by summarizing evidence from preclinical to clinical research, focusing on the role of GM and its derived metabolites, including short-chain fatty acids, bile acids, lipopolysaccharides, and neurotransmitters. Mechanistic exploration provides novel insights for developing microbiota-targeted therapeutic strategies, such as dietary and lifestyle interventions, fecal microbiota transplantation, probiotics, and traditional Chinese medicine, paving the way for promising approaches to prevent and manage PP.

Introduction: Structural variations (SVs)—large, functionally consequential genomic alterations—serve as high-resolution markers for strain-level differentiation in the human microbiome, yet their relevance to vertical transmission of the maternal microbiota and early-life colonization remains unclear. Methods: Using metagenomic data from a 98-pair longitudinal mother-infant cohort and a 25-pair multi-niche cohort, we profiled microbial taxa, functions, and SVs, characterized variable SVs (vSVs), deletion SVs (dSVs), and transmitted SVs (tSVs), and evaluated the potential influence of delivery mode, feeding regimen, and maternal ecological niches. Results: We identified 5,578 SVs across 51 reference strains, with infants showing increasing SV diversity during the first year of life, and observed significantly greater SV similarity within mother-infant pairs than unrelated pairs. Abundance-based analysis identified 90 microbial species shared between mothers and infants. However, when incorporating SV-based tracking, only 14 strains showed patterns consistent with sustained maternal contribution across time points. Furthermore, exploratory subgroup analyses suggested that both delivery mode and feeding regimen may influence the vertical transmission patterns of maternal microbial strains and transmitted SVs. Functionally, tSVs were enriched in pathways linked to carbohydrate, amino acid, and lipid metabolism, as well as transport and environmental adaptation modules such as T4SS. Multi-niche analysis further suggested that the maternal gut showed the strongest inferred signal of SV-supported strain sharing with both the infant gut and oral microbiota. Discussion: Together, these findings suggest that microbial SVs can serve as complementary markers for investigating maternal contribution and vertical transmission-related strain-level patterns in early-life microbiome development, providing new insights into microbial inheritance and early-life health trajectories.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition arising from interactions between genetic and environmental factors. The interplay between the microbiota-gut-brain axis and epigenetics has been implicated in ASD, but the extent of their impact remains unclear. We hypothesized that parental gut microbiota dysbiosis shapes cross-generationally shared DNA methylation patterns and ASD-like phenotypes in offspring. Antibiotic-treated adult mice were colonized with fecal microbiota from children with ASD or typically developing (TD) controls, then bred. Colonization with ASD-associated microbiota did not alter parental behavior but induced ASD-like behavioral changes in offspring, accompanied by colonic inflammation and neuronal loss in the hippocampus and striatum. Targeted bisulfite sequencing revealed that ASD-associated microbiota reshaped methylation at ASD-related CpG sites in parental brain, blood, and colon, with a subset of these alterations also observed in offspring tissue. Integrative analyses revealed sex-specific networks linking gut microbes, DNA methylation, gene expression, metabolites, and behavior. These findings support a model in which parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation changes linked to ASD-like phenotypes in offspring. Together, these results provide novel microbial and epigenetic insights into ASD-related risk and offering a plausible mechanistic explanation for the clinical phenomenon in which unaffected parents give rise to children with ASD.

Approximately 85–90% patients with small for gestational age (SGA) experience catch-up growth (CUG) by the age of 2, with their height reaching ͨ