<i>Limosilactobacillus reuteri</i> NCU-37 alleviates leuprorelin-induced perimenopausal syndrome in infertile women by modulating the gut microbiota: a randomized controlled trial

Leuprorelin-induced perimenopausal syndrome (LIPS) represents a common challenge faced by infertile women undergoing assisted reproductive procedures, characterized primarily by hot flashes, night sweats, and mood swings. Currently, there is a shortage of safe approaches that can effectively alleviate these symptoms without compromising the therapeutic outcomes of pregnancy. In this study, 100 infertile women with LIPS (placebo group, MP group; probiotic group, ML group) and 50 healthy women were enrolled to evaluate the therapeutic effects of <i>Limosilactobacillus reuteri</i> NCU-37 on LIPS. The results showed that, compared to the MP group, NCU-37 significantly reduced the Modified Kupperman Index (MKI) scores (MP <i>vs.</i> ML = 15.00 <i>vs.</i> 8.00, <i>p</i> < 0.01), Hamilton Anxiety Scale (HAMA) scores (11.50 <i>vs.</i> 7.00, <i>p</i> < 0.01), Hamilton Depression Scale (HAMD) scores (9.00 <i>vs.</i> 7.00, <i>p</i> < 0.01), and Athens Insomnia Scale (AIS) scores (7.50 <i>vs.</i> 5.00, <i>p</i> < 0.05). Additionally, NCU-37 significantly increased serum hormone levels, including anti-Müllerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), compared to the placebo group (<i>p</i> < 0.05). These results indicate that NCU-37 effectively improves perimenopausal symptoms, mood disorders, and hormone levels. Meanwhile, NCU-37 altered the composition and diversity of the gut microbiota in LIPS patients, resulting in a significant increase in beneficial bacteria (<i>Blautia</i>) and a reduction in pathogenic bacteria (<i>Bacteroides</i>). Interestingly, NCU-37 increased the pregnancy rate in LIPS patients. In conclusion, this study demonstrates for the first time that the probiotic NCU-37 alleviates LIPS by improving perimenopausal symptoms, mood disorders, hormone levels, and the gut microbiota, thereby providing data to support its clinical application.