Hwang HJ, et al. Nutr Res Pract. 2019 Apr;13(2):105-114. https://doi.org/10.4162/nrp.2019.13.2.105

The link between gut microbiota and precocious puberty has garnered increasing attention; however, the underlying mechanisms remain poorly understood, and most existing studies are cross-sectional, making it difficult to capture the longitudinal changes in gut microbiota throughout precocious puberty. Here, female rats were fed high-fat diets supplemented with antibiotics to establish a model of precocious puberty with gut microbiota perturbation. Gut microbiota dynamics were characterized based on stool samples collected at postnatal day (PND) 21, 25, 29, and 33. Serum metabolomic profiles on PND 33 were analyzed to investigate the potential mechanisms by which gut microbiota may influence precocious puberty. We found that alterations in gut microbiota alleviated high-fat diet-induced precocious puberty. Temporal changes in gut microbiota that potentially regulate precocious puberty were identified, with specific contributions from Lactobacillus intestinalis , Romboutsia , Lactobacillus , and others. Additionally, the modified gut microbiota ameliorated the dysregulation of steroid hormones, bile acids, and lipid molecules at PND 33. Notably, lysoPE 16:0, 23-nordeoxycholic acid, and psoralidin were not only influenced by the gut microbiota but also closely associated with indicators of pubertal development. This study highlights key gut microbiota and metabolites that may inform future mechanistic studies and intervention strategies for managing precocious puberty. IMPORTANCE: Previous studies have highlighted the link between gut microbiota and precocious puberty. Our research further explored this connection, demonstrating that microbial shifts modulated the onset and progression of precocious puberty, characterized by increased hypothalamic sirtuin-1 gene expression and decreased kisspeptin-1 and gonadotropin-releasing hormone gene expressions. At the same time, we explored the longitudinal trajectories of the gut microbiota and identified the key microbes involved in regulating precocious puberty, including Romboutsia , Lactobacillus , and others. In addition, an integrated analysis of the microbiome and metabolome revealed specific bacteria and metabolites that contribute to the onset of puberty. These findings offer valuable insights into the mechanisms driving precocious puberty and may inform future research and potential therapeutic interventions.

As the predominant constituents of the vaginal microbiome in healthy women, Lactobacillus species are considered essential in maintaining a homeostatic vaginal microbiome. Specific Lactobacillus species can produce beneficial metabolites to support their persistence within the host environment and inhibit Candida albicans colonization. Due to the extensive diversity of Lactobacillus species and their metabolites, comprehensively investigating all possible interactions remains challenging. This study employed an integrative approach combining genome-scale metabolic modeling, metagenomic sequencing, and in vitro validation to explore Lactobacillus and C. albicans interactions. Pairwise simulations of 159 Lactobacillus strains with C. albicans revealed that most strains exhibit inhibitory effects, altering fungal amino acid and carbohydrate metabolism. Key inhibitory metabolites identified included formate, L-lactate, and L-malate. Metagenomic analysis of vaginal swabs from 20 vulvovaginal candidiasis (VVC) patients and 20 healthy women showed a correlation between Lactobacillus species abundance and reduced C. albicans colonization. In vitro experiments confirmed the inhibitory effects of these metabolites and the selected Lactobacillus strains on C. albicans growth, thereby validating our computational predictions. These findings provide insights into the metabolic interactions within the vaginal microbiome and pave the way for targeted microbial or metabolite-based therapeutic strategies to manage VVC. IMPORTANCE: Vulvovaginal candidiasis is a prevalent fungal infection with significant implications for women’s health, caused primarily by Candida albicans . Although the protective role of a Lactobacillus -dominated vaginal microbiome is well established, the metabolic mechanisms underlying the interactions between Lactobacillus species and C. albicans remain inadequately understood. Specifically, the Lactobacillus species that effectively inhibit C. albicans and the metabolic pathways involved warrant further investigation. This study offers novel insights into the metabolic mechanisms underlying Lactobacillus antagonism against C. albicans . By identifying critical metabolic pathways and inhibitory metabolites, this study enhances our understanding of vaginal microbiome dynamics and host-microbe interactions. The findings suggest that key Lactobacillus strains and their metabolites could significantly reduce harmful levels of C. albicans , paving the way for future therapeutic strategies that leverage these microbial characteristics to promote vaginal health.

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.