Abstract
Premenstrual syndrome (PMS) is characterized by periodic physical and psychological symptoms during the menstrual cycle of women of reproductive age. This study aimed to investigate the effects of Lactobacillus helveticus HY7801 (HY7801) on PMS-related hormonal and inflammatory responses, with a specific focus on its influence on the composition of the gut microbiota and the functional role of HY7801-derived extracellular vesicles (EVs). Data from a metoclopramide (MCP)-induced hyperprolactinemia mouse model showed that oral administration of HY7801 reduced serum levels of prolactin and pro-inflammatory cytokines significantly, while restoring hormone imbalances caused by MCP. HY7801 also altered the composition of the gut microbiota by decreasing the relative abundance of Desulfovibrionaceae, Staphylococcaceae, and Bacteroidaceae, which are bacterial families associated with mental health disorders. The abundance of these taxa correlated positively with prolactin and cytokine levels. Furthermore, HY7801-derived EVs were identified as functional bioactive components that exert cytoprotective effects and suppress prolactin secretion significantly in estradiol-stimulated GH3 cells. These findings indicate that HY7801 alleviates PMS symptoms, not only by modulating gut microbiota but also through direct cellular mechanisms mediated by its EVs. Taken together, these dual mechanisms suggest that HY7801 and its secreted components represent a promising approach to management of PMS symptoms.