Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis

Abstract

Although a few studies have investigated the intestinal microbiota of women with polycystic ovary syndrome (PCOS), the functional and metabolic mechanisms of the microbes associated with PCOS, as well as potential microbial biomarkers, have not yet been identified. To address this gap, we designed a two-phase experiment in which we performed shotgun metagenomic sequencing and monitored the metabolic parameters, gut-brain mediators, and sex hormones of PCOS patients. In the first stage, we identified an imbalance in the intestinal microbiota of the PCOS patients, observing that Faecalibacterium, Bifidobacterium, and Blautia were significantly more abundant in the control group, whereas Parabacteroides and Clostridium were enriched in the PCOS group. In the second stage, we monitored the impact of the probiotic Bifidobacterium lactis V9 on the intestinal microbiome, gut-brain mediators, and sex hormones of 14 PCOS patients. Notably, we observed that the levels of luteinizing hormone (LH) and LH/follicle-stimulating hormone (LH/FSH) decreased significantly in 9 volunteers, whereas the levels of sex hormones and intestinal short-chain fatty acids (SCFAs) increased markedly. In contrast, the changes in the indices mentioned above were indistinct in the remaining 5 volunteers. The results of an analysis of the number of viable Bifidobacterium lactis V9 cells in the two groups were highly consistent with the clinical and SCFA results. Therefore, effective host gut colonization of the probiotic Bifidobacterium lactis V9 was crucial for its ability to function as a probiotic. Finally, we propose a potential mechanism describing how probiotics regulate the levels of sex hormones by manipulating the intestinal microbiome in PCOS patients. IMPORTANCE Polycystic ovary syndrome (PCOS) is a common metabolic disorder among women of reproductive age worldwide. Through a two-phase clinical experiment, we first revealed an imbalance in the intestinal microbiome of PCOS patients. By binning and annotating shotgun metagenomic sequences into metagenomic species (MGS), 61 MGSs were identified as potential PCOS-related microbial biomarkers. In the second stage, we monitored the impact of the probiotic Bifidobacterium lactis V9 on the intestinal microbiota, metabolic parameters, gut-brain mediators, and sex hormones of PCOS patients. Notably, we observed that the PCOS-related clinical indices and the intestinal microbiotas of the participating patients exhibited an inconsistent response to the intake of the B. lactis V9 probiotic. Therefore, effective host gut colonization of the probiotic was crucial for its ability to function as a probiotic. Finally, we propose a potential mechanism by which B. lactis V9 regulates the levels of sex hormones by manipulating the intestinal microbiome in PCOS patients.

Probiotics Dietary Supplementation for Modulating Endocrine and Fertility Microbiota Dysbiosis

“…All studies showed a significant improvement in the clinical status of the patient groups that received specific strains of Lactobacillus [21,23,31,32]. In the case of PCOS patients, one study administered Bifidobacterium lactis V9 to 14 patients and showed positive modulation capacities of sex hormone levels [33]. Moreover, the controlled administration of probiotics during pregnancy, microbiota disorders allowed us to select only two clinical studies, but the sample size was insufficient to conclude specific modulation capacities [18,34].…”

“…We further reviewed, extracted and highlighted the relevant information from the selected studies. Therefore, the study carried out by Zhang et al [33] in PCOS patients revealed the relevance of determining the individual physiological status before administering the probiotics to be tested. Data determinations on microbiota compositional variability, key metabolites (SCFA, TC), gut-brain mediators (Ghrelin, PYY) and sex hormones levels were decisive for the outcome comparisons.…”

“…Moreover, Valcarce et al [40] studied in animal models the effects of Lactobacillus rhamnosus CECT8361 and Bifidobacterium longum CECT7347 on sperm quality finding an improvement of the parameters, these probiotics were selected because of its antioxidant and anti-inflammatory activities [40,76]. On the other hand, probiotics of the genus Bifidobacterium have been used for the treatment of PCOS, specifically the strain Bifidobacterium lactis V9, previously tested by Zhang et al [33] and selected for exhibiting excellent probiotic characteristics.…”

Naringenin, a Flavonoid, Modulates Gut Microbiome and Ameliorates Hormone Levels to Improve Polycystic Ovary Syndrome in Letrozole-induced Rats 

“…Studies showed that the gut microbiota can induce or regulate insulin resistance and chronic in ammation, and can also regulate sex hormone levels [7][8][9]. Meanwhile, with the deepening of research, accumulating evidence showed that intestinal ora is closely related to the occurrence and development of PCOS [1,8,10]. Such as, transplanting feces of PCOS patients into mice can cause PCOS phenotype in mice [10], both PCOS patients and animal models, PCOS-induced changes in the gut microbiota alpha and beta diversity can occur to a certain extent [3].…”

“…Meanwhile, with the deepening of research, accumulating evidence showed that intestinal ora is closely related to the occurrence and development of PCOS [1,8,10]. Such as, transplanting feces of PCOS patients into mice can cause PCOS phenotype in mice [10], both PCOS patients and animal models, PCOS-induced changes in the gut microbiota alpha and beta diversity can occur to a certain extent [3]. In addition, the clinical manifestations of PCOS were signi cantly reduced in obese women treated with low-fat diet [11], and emerging evidence showed that the composition of the intestinal ora may affect women's metabolic homeostasis and reproductive tness [12].…”