Symptom-linked disruption of the vaginal Lactobacillus-IL-2/IFN-γ axis in genitourinary syndrome of menopause related symptoms.

Genitourinary syndrome of menopause (GSM) is a common disease; however, the underlying mechanisms are unclear. This study aimed to identify the vaginal cytokine and microbiome signatures associated with symptom severity and explore the immune-microbial interactions underlying GSM. Vaginal fluid samples were collected from 66 women (42 controls and 24 patients with GSM). Cytokine levels were measured using a 25-cytokine multiplex assay. Microbiome profiles were obtained by 16S ribosomal RNA sequencing of the same samples; 61 samples passed quality control (37 controls, 24 patients). Most cytokines were downregulated in patients compared with controls, with interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 showing the greatest reductions. Cytokine levels were negatively correlated with symptom severity, independent of menopausal status. Among post-menopausal women, IL-2 and IFN-γ levels were significantly lower in those with severe symptoms. Microbiome analysis revealed reduced alpha diversity and depletion of the Lactobacillus species, especially L. crispatus and L. iners, with increased levels of intestinal bacteria such as Enterococcus and Bacteroides. Correlation analysis demonstrated a strong positive association between L. crispatus and IL-2 (r = 0.56, p < 0.05) and a weaker trend with IFN-γ. Vaginal cytokine and microbiome profiles were altered in proportion to symptom severity, rather than menopausal status. The IL-2-Lactobacillus crispatus axis appears to help maintain the mucosal immune balance, suggesting its potential diagnostic and therapeutic value for restoring immune-microbial homeostasis in patients with vaginal atrophy.