Probiotics plus Prebiotics Improves PCOS Weight Loss

Effects of synbiotic supplementation and lifestyle modifications on women with polycystic ovary syndrome

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Background

The Dysbiosis of Gut Microbiota (DOGMA) theory states that poor diet can alter bowel bacterial flora leading to an increase in gut mucosal permeability and therefore circulating levels of lipopolysaccharides (LPS) in women with PCOS.

It also states this increase in LPS activates the immune system, causing insulin resistance, compensatory hyperinsulinemia and increased androgen production by the ovaries.

Previous studies show endotoxemia (endotoxins) is caused by elevated levels of LPS and LPS binding proteins which interestingly correlates with testosterone levels and hirsutism. 

Two meta-analysis of probiotics and synbiotic (probiotic plus prebiotic) studies, in women with PCOS, showed a decrease in blood sugar and fasting insulin levels, improved insulin sensitivity, reduction in triglycerides and also testosterone without any change in weight.

However whether or not the addition of probiotics / synbiotics to lifestyle modification, can intensify the effect on weight loss and testosterone levels, in women with PCOS is currently unknown.

Aim

To evaluate the effects of lifestyle modifications and synbiotic supplementation on PCOS.

Methodology

In this randomized double-blinded, placebo-controlled trial a total of 65 women with PCOS (Rotterdam criteria) and BMI>25 was recruited by the Reproductive Endocrinology & Infertility Clinical Services (Poznan University of Medical Sciences).

Women with congenital adrenal hyperplasia, hyperprolactinemia, thyroid disease, Cushing disease and diabetes mellitus were automatically excluded from the study to minimise bias. Similarly, none of the participants had used any type of hormonal therapy, antibiotics, laxatives, weight loss supplements, probiotics or synbiotics two months prior to beginning this study.

The women were then randomized into two groups (Synbiotic or Placebo) with both investigators and women blinded to their assigned group. 

The Synbiotic group (n= 30) were allocated 4 capsules a day, for a study period of 3 months. The capsules contained probiotics: Bifidobacterium lactis (W51, W52), Lactobacillus acidophilus (W22), Lactobacillus paracasei (W20), Lactobacillus plantarum (W21, Lactobacillus salivarius (W24), Lactobacillus lactis (W19) and prebiotics: fructooligosaccharides and inulin. Alternatively, the Placebo control group (n = 35) were allocated 4 capsules a day, containing a placebo, for their 3 month period.

Lifestyle modification consisted of a monitored diet and exercise program. More specifically restriction of caloric intake (1400 – 1800kcal/day), individual food advice by a dietician, no alcohol and 30-40 minutes of walking a day.

Participants were assessed twice, initially at the start of the study and then at the end of the study. Clinical assessments included BMI, body fat, hirsutism, acne score, ovarian volume, glucose and insulin levels, total testosterone, LH, FSH, SHBG, 17-hydroxyprogesterone, DHEAS, total cholesterol and triglycerides.

Results

Of the initial 65 women, 39 completed the study (Symbiotic = 20, Placebo = 19) of which 33 had hyperandrogenism. Baseline characteristics comparing the 2 groups identified no statistically significant differences between them however total testosterone and DHEAS was slightly higher in the control group.

Following treatment 38 of the 39 women achieved the primary outcome of weight loss. In the Placebo group, significant decreases were seen in BMI (-5%), body fat (-2.7%), waist (-6.3cm), hip (-11.5cm) and thigh (-3.8cm) circumferences.

Similarly, in the Synbiotic group, significant decreases were also seen in BMI (-8%), body fat (-3.9%), waist (-10.7cm), hip (-10.2cm) and thigh (-4.3cm) circumferences. Of note, the decrease in waist circumference was significantly greater compared to the placebo control group.

In addition, a significant decrease in total testosterone levels occurred in 53% and 90% of women in both the Placebo and Synbiotic groups respectively. This caused an overall decrease in testosterone levels, of 6% in the Placebo group and 32% in the Synbiotic group, which was significantly greater (P=0.016). A trend towards decreased hirsutism and improved insulin sensitivity was noted however it was not statistically significant in this study size.

Lastly, in the Synbiotic group a 23% decrease in triglycerides was seen, compared to only -15% in the Placebo group, with DHEAS significantly increased (14%) by the addition of synbiotics.

Limitations

1. High drop out rate reduced final group sizes limiting the potential for further statistically significant outcomes.
2. Short study duration may not have shown the full effect of Synbiotics especially on hirsutism or lipid profile.

Funding

No external funding was declared for this study.

Similar studies

Banaszewska B, et al. (2020). Elevation of markers of endotoxemia in women with polycystic ovary syndrome. https://doi.org/10.1093/humrep/deaa194

Hadi A, et al. (2020). Effect of probiotics and synbiotics on selected anthropometric and biochemical measures in women with polycystic ovary syndrome: a systematic review and meta-analysis. https://doi.org/10.1038/s41430-019-0434-9

Liao D, et al. (2018). Meta-analysis of the effects of probiotic supplementation on glycemia, lipidic profiles, weight loss and C-reactive protein in women with polycystic ovarian syndrome. https://doi.org/10.23736/s0026-4806.18.05728-2

Torres P J, et al. (2018). Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism. https://doi.org/10.1210/jc.2017-02153

Lindheim L, et al. (2017). Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study. https://doi.org/10.1371/journal.pone.0168390

Liu R, et al. (2017). Dysbiosis of Gut Microbiota Associated with Clinical Parameters in Polycystic Ovary Syndrome. https://dx.doi.org/10.3389/fmicb.2017.00324

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