Study on gut microbiota and metabolomics in postmenopausal women Original paper

What was studied?

This research investigated the interplay between gut microbiota composition, fecal metabolites, and clinical symptoms in perimenopausal women, with a particular focus on the influence of follicle-stimulating hormone (FSH) levels. Using 16S rRNA gene sequencing and untargeted metabolomic profiling, the study analyzed stool samples from 44 women experiencing perimenopausal symptoms to determine differences in microbial diversity, specific microbial taxa, and metabolic pathways associated with varying FSH levels. The research aimed to elucidate how fluctuations in reproductive hormones, particularly FSH, are linked with changes in the gut microbiome and metabolic signatures, and how these biological variations correspond to clinical manifestations such as hot flashes, bone pain, and mental disturbances.

Who was studied?

The study cohort comprised 44 outpatient perimenopausal women, divided into two groups based on FSH levels: Group 1 (G1, n=16) had FSH <40 iu l (indicative of declining ovarian reserve), and group 2 (g2, n=28) had fsh>40 IU/L (indicative of premature ovarian failure). Demographic and hormonal profiles were similar between groups except for differences in FSH, LH, E2, and progesterone levels. Symptoms were categorized and quantified using the K-score. The G1 group experienced more mental disorders (anxiety, insomnia, depression), while the G2 group had a higher prevalence of hot flashes and bone pain. Age, testosterone, and prolactin did not differ significantly between the groups, minimizing confounding effects from these variables.

Most important findings

The study found no significant difference in overall microbial diversity (alpha or beta diversity) between the two FSH-defined groups. However, there were notable shifts in the relative abundance of specific bacterial taxa. At the genus level, Faecalibacterium, Subdoligranulum, Agathobacter, and Roseburia were more abundant in G1, while Bacteroides, Escherichia-Shigella, Bifidobacterium, and Blautia were more abundant in G2. Importantly, Bacteroides implicated in bone health was higher in G2, which also had a greater prevalence of bone pain. Bifidobacterium, associated with mitigating mental disorders, was also elevated in G2, where mental symptoms were less common. Spearman correlation analyses revealed that FSH was negatively correlated with Subdoligranulum and Agathobacter, while estradiol was positively correlated with Faecalibacterium and unclassified Lachnospiraceae. Metabolomic analysis revealed significant upregulation of metabolites involved in tyrosine metabolism, alpha-linolenic acid metabolism, and other lipid pathways in G2, which aligns with emerging evidence linking lipid metabolism disorders to postmenopausal osteoporosis. Several metabolites showed strong correlations with specific bacterial genera, highlighting potential microbiome-metabolite axes relevant to symptomatology.

Key implications

This study adds to the growing evidence linking perimenopausal hormonal changes, particularly elevated FSH, with specific alterations in the gut microbiome and fecal metabolome. The observed associations between certain bacterial taxa (e.g., Bacteroides, Bifidobacterium, Faecalibacterium, Blautia) and clinical symptoms suggest that the gut microbiota may modulate the risk or severity of common perimenopausal manifestations such as bone pain, hot flashes, and mental disorders. The enrichment of lipid and amino acid metabolism pathways in women with higher FSH and more pronounced bone pain supports the potential utility of microbiome and metabolome profiling in risk stratification and therapeutic targeting. While the study is limited by its small sample size, the findings indicate that microbiome signatures could serve as biomarkers for symptom phenotyping and inspire novel interventions, such as targeted probiotics or dietary modifications, to improve quality of life in perimenopausal women.