Can probiotics reverse early ovarian decline? A new study in mice suggests they might restore hormonal balance and microbial health after chemotherapy-induced damage.
Study: Probiotics may improve vaginal microbiota, metabolic disorders and ovarian function-related markers by modulating gut microbiota in POI mice. Image credit: ALIOUI MA/Shutterstock.com
A study conducted by Nanjing Medical University researchers revealed that probiotics can potentially improve ovarian functions and gut and vaginal microbiota compositions in mice with premature ovarian insufficiency, a condition characterized by early deterioration of ovarian function. The study was published in BMC Microbiology.
Background
Premature ovarian insufficiency (POI) is a condition of premature menopause, causing deterioration of ovarian functions before the age of 40 years. The condition is characterized by abnormal menstruation and hormonal imbalance.
Women with POI experience a range of short-term and long-term health complications, which collectively affect their mental health and overall quality of life. Apart from increasing the risk of osteoporosis, cardiovascular disease, and cognitive impairment, POI can potentially affect fertility.
Existing evidence on the pathophysiology of POI indicates that the condition can lead to changes in gut and vaginal microbiota compositions, and that these changes are associated with hormonal imbalance observed in women with POI.
Given the potential link between microbial composition and POI pathophysiology, researchers at the Nanjing Medical University, China, conducted this study in a chemotherapy-induced mouse model of POI to investigate the effect of probiotics on the composition of gut and vaginal microbiota, markers of ovarian function, and markers of lipid metabolism.
Probiotics are a class of microorganisms that promote the growth of beneficial bacterial populations and suppress the growth of harmful bacteria. This leads to improvements in gut microbiota and a range of physiological processes in the host’s body.
The study
The researchers generated a mouse model of POI by injecting cyclophosphamide, a chemotherapeutic drug that damages ovarian follicles. They randomly divided these mice into the POI and probiotic-treated POI groups and used healthy mice as controls.
The mice in the treatment group received a mixture of 12 probiotics for 28 consecutive days, while the control and the POI group mice received normal saline for the same duration.
Blood samples collected from the mice following treatment completion were analyzed for anti-Müllerian hormone (a crucial hormone for reproductive development) and sex hormone levels, the number of follicles, and serum levels of total cholesterol and triglycerides. The gut and vaginal microbiota compositions were analyzed using fecal and vaginal samples, respectively.
Key findings
The analysis of mice with POI revealed significantly lower levels of anti-Müllerian hormone and growing ovarian follicles and significantly higher levels of atretic follicles (degenerated ovarian follicles) than healthy mice. The POI mice also exhibited impairments in gut and vaginal microbiota.
Regarding the effect of the study intervention, the study reported that 28-day probiotic treatment caused non-significant (P > 0.05) but trending improvements in ovarian function markers, including anti-Müllerian hormone and estradiol levels, in mice with POI. The treated mice also exhibited a slight increase in growing follicle numbers and a notable, though not statistically significant, decrease in degenerated follicle numbers compared to untreated mice with POI.
The probiotic treatment caused a slight reduction in serum levels of total cholesterol and triglycerides, with a statistically significant decrease observed in triglycerides, indicating possible metabolic improvements in POI mice.
Regarding microbial compositions, the study found that the probiotic treatment significantly altered the gut microbiota, leading to restoration of microbial compositions to levels that trended towards those of healthy mice.
While alpha diversity measure of gut and vaginal microbiota did not differ significantly amoung groups (P > 0.05), beta diversity and microbial composition showed notable shifts with probiotic treatment.
Probiotic treatment also increased the abundance of beneficial bacteria in the vagina, particularly Rodentibacter, with bacterial populations even exceeding those in the control group; however, the health implications of this increase require further study.
Study significance
The study highlights that probiotics may help mitigate ovarian dysfunction, improve lipid metabolism, and restore vaginal microbiota homeostasis in POI mice by modulating gut microbiota composition.
Existing evidence regarding reproductive endocrine diseases suggests a link between gut and vaginal microbiota disruption, which in turn is associated with the progression and outcome of diverse reproductive endocrine disorders, including polycystic ovary syndrome and endometriosis. The gut microbiota plays a vital role in shaping various physiological functions, including immune, neurological, metabolic, and endocrine functions. Recent evidence indicates that both gut and vaginal microbiotas are involved in the regulation of sex hormones and female reproductive system.
Scientific literature also documents that gut microbiota alterations can remotely affect vaginal immunity through the modulation of circulating immune cells. Gut microbiota-derived metabolites, such as short-chain fatty acids, can reach the vagina through circulation and modulate the vaginal microenvironment.
Given the study findings, the researchers suggest that probiotics could offer a promising avenue for future therapeutic development. However, they emphasize that clinical trials in humans are needed to confirm these effects. The current results are based on a preclinical mouse model, and direct clinical application in women with POI is not yet supported by sufficient evidence.
Probiotics may help alleviate clinical symptoms, such as atrophic vaginal inflammation and metabolic syndrome, and improve long-term quality of life in women living with POI.
Future studies should focus on exploring specific mechanisms involved in probiotic-mediated regulation of microbial composition and improvement of ovarian functions to clinically establish the therapeutic potential of probiotics in patients with chemotherapy-induced ovarian insufficiency. The researchers noted that clinical studies in human populations are currently underway.
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