INTRODUCTION:

Polycystic ovarian syndrome (PCOS) affects around 8–13% of reproductive-age women. As per WHO report up to 70% of women who are affected by the syndrome go undetected worldwide. PCOS is the most typical reason for anovulation and a major cause of infertility and is linked to a number of long-term health issues that impact both physical and emotional well-being¹. It is a common endocrine condition affects how the ovaries work and it’s characterized by a number of features. Small underdeveloped cysts may develop in the ovaries, affecting the menstrual cycle as some of the sacs are unable to release an egg, preventing ovulation. Another characteristic feature of PCOS is also characterized by an imbalance in sex hormones, so the ovaries produce excess androgens and release them into the body². Although androgens are natural constituents of a woman's body since they are turned into estrogen, high levels have been related to PCOS and other health problems. PCOS is a complex condition with no known cause or cure, and it is not thought to be hereditary; instead, it is commonly connected with high hormone levels such as insulin. Women with this illness commonly develop insulin resistance, which occurs when their bodies grow resistant to the effects of insulin, prompting the pancreas to produce more insulin³. This may contribute to a variety of serious health issues, including type 2 diabetes, obesity, and testosterone overproduction, which can interfere with ovulation. According to estimates, PCOS affects five to twenty percent of women of reproductive age around the world. Androgen excess in women with PCOS harms a variety of metabolic tissues, including adipose tissues, the liver, the pancreas, and the skeletal muscles⁴. Increased the level of androgens inhibits systemic metabolism through the brain, particularly increasing obesity and decreasing insulin sensitivity.The microbiome is the collection of microbes that naturally dwell inside our bodies, including bacteria, fungi, viruses, and their genes.The microbiota has a significant impact on many vital functions in the human body. It helps regulate the immune system, digest food, produce vitamins like B12 and K, metabolize xenobiotic compounds, and perform a variety of other functions⁵. This review provides an overview about probiotics and its role in the management of PCOD

Probiotics in PCOD:

Probiotics are living microorganisms, generally bacteria and yeasts, that have been scientifically shown to promote health when ingested in sufficient quantities. These microbes are commonly referred to as "good" or "friendly" bacteria because of their positive effects on gut health and overall well-being⁶. The importance of probiotics in the treatment of Polycystic Ovary Syndrome (PCOS) is an area of ongoing research, and the potential benefits are not yet fully established. Evidence reveals that almost 70% of the immune system is involved with the gastrointestinal (GI) tract to maintain its health and function through synergistic interactions with numerous bacteria colonies (flora) that exist in our GI tract⁷. Imbalances in this gut flora, such as a lack of good bacteria or a proliferation of harmful species, can have a negative impact on human health. Unbalanced gut flora can cause abdominal pain, bloating, gas, constipation, diarrhoea, and a weakened immune system⁸. The health of our gut flora is influenced by antibiotic medication, disease, poor diet, stress, and environmental pollutants. In the past, eating fermented foods on a daily basis helped to maintain healthy gut flora. Probiotic therapy is a novel approach to maintain normal body mass index (BMI), tolerance to insulin, levels of lipids, and other PCOS-related characteristics through several mechanisms⁹.

Gut Microbiota:

The term "gut microbiota" refers to the complex population of microorganisms found in the digestive tract, which includes bacteria, fungus, viruses, and other microbes. The gut microbiome is extremely important in various physiological functions and has a profound impact on overall health. There is evidence to suggest that individuals with PCOS may have alterations in their gut microbiota^10,11. An imbalance in gut microbiota, known as dysbiosis, has been connected with various metabolic disorders, including PCOS. Probiotics aim to restore or maintain a healthy balance of gut bacteria. These products can modulate the composition of the gut microbial population, improve leaky gut, reduce gastrointestinal permeability, and reduce the levels of intestinal lipopolysaccharideor endotoxin concentrations^12,13. The communication pathway between the gut microbiota and the brain, specifically involving signals in the hypothalamus is also recognized to have an essential role in hunger, body weight, and whole-body metabolism regulation. The gut microbiota has the ability to influence the neural system by generating and releasing neuroactive substances, especially neurotransmitters like melatonin, 5-hydroxytryptamine, norepinephrine, and hormones such as gamma-aminobutyric acid (GABA)¹⁴. They also produce metabolites such as monoamines, methionine, glutamate, and homocysteine, which have the ability to alter nervous system function and modulate behaviours. The gut microbiota generates neurotoxic substances like D-lactic acid, pro-inflammatory cytokines, homocysteine and ammonia. These substances have the potential to traverse the blood-brain barrier, entering the brain and influencing the gut-microbiota-brain axis through immune responses, neuroendocrine pathways, and direct nervous mechanisms^15,16.Recent research suggests that gut microbiota and probiotics may play an important role in addressing the complications of PCOD, such as inflammation, insulin resistance, and obesity.

Inflammation and Insulin Resistance:

Chronic low-grade inflammation playsan important role in the development and progression of Polycystic Ovary Syndrome (PCOS). Inflammation directly and indirectly affects insulin sensitivity causes the development of hormonal imbalances and metabolic disturbances. One of the primary features of PCOS is insulin resistance, which is intimately related to persistent low-grade inflammation^17,18. Increased insulin resistance may result from compromised insulin signalling, which is facilitated by inflammation. One typical hallmark of PCOS is impaired insulin sensitivity, also known as diminished responsiveness to insulin, which is closely associated with persistent low-grade inflammation. It might be a factor in decreased insulin signalling, which would raise insulin resistance. Inflammation may have a role in hyperandrogenism, which results in an imbalance in the synthesis and control of hormones¹⁹.Inflammation may also play a role in disruptions to the normal ovarian function, contributing to irregular menstrual cycles and anovulation in women with PCOS.Oxidative stress arises from an imbalance in the generation of reactive oxygen species (free radicals) and the body's capacity to detoxify them. Oxidative stress leads to complications of PCOD including metabolic abnormalities leads to obesity, dyslipidaemia, and increased risk of type 2 diabetes^20,21.

Probiotics may have anti-inflammatory effects and could potentially contribute to reducing insulin resistance, a common feature in PCOS. By reducing inflammation, probiotics may contribute to increased insulin sensitivity and other metabolic parameters associated with PCOS^22,23. Literature suggests that the use of certain probiotic strains can augment insulin sensitivity. Some probiotic strains like Lactobacillus acidophilus, Bifidobacterium species, Lactobacillus plantarum, Propionibacterium freudenreichii and Akkermansia Muciniphila Generate bioactive substances, such as short-chain fatty acids (SCFAs)²⁴. Acetate, lactate, butyric acid and propionic acids are the prevalent short-chain fatty acids which have anti-inflammatory properties. These compounds can help regulate the immune system and reduce inflammation in the body Moreover, the effects of SCFAs can be strain specific, and the specific health effects may depend on factors such as the dosage, the individual's health status, and the overall composition of the gut microbiota. Some probiotic strains have demonstrated anti-inflammatory activities via decreasing pro-inflammatory cytokine production and increases the secretion of anti-inflammatory compounds^25,26.

Obesity and Weight management:

Some studies suggest that individuals with PCOS may have alterations in the regulation of appetite and may experience increased feelings of hunger and food intake. This can lead to higher calorie intake and contribute to obesity. PCOS is often associated with challenges in weight management. Insulin resistance, leptin resistance and ghrelin Imbalance are the major mechanisms by which PCOS may contribute to increased feelings of hunger and alterations in appetite, ultimately leading to obesity, is complex and involves various hormonal and metabolic factors. Leptin and ghrelin are the hormone helps regulate appetite and energy balance^27,28. In PCOS, individuals may develop leptin and ghrelin resistance. This means that despite having elevated levels of leptin (indicating sufficient fat stores) and ghrelin, the brain doesn't receive the signal to reduce appetite and increase energy expenditure results in obesity. Some studies suggest that probiotics may play a role in weight management and could potentially contribute to modulate appetite hormones. Gut microbiota can influence hormones related to appetite regulation. Probiotics may play a role in modulating hunger (ghrelin) and satietyhormones (leptin)^29,30. It plays a role in fermenting dietary fibers and generating short-chain fatty acids (SCFAs). SCFAs can influence energy metabolism and appetite. Probiotics may contribute to a healthier gut environment, promoting the production of beneficial SCFAs and influencing energy balance. Some probiotics have the ability to metabolize dietary components, including certain types of fibers. This can lead to the production of metabolites that may influence metabolic processes and potentially impact body weight³¹. PCOS elevates the risk of other problems such as cardiac disorders, type 2 diabetes, metabolic syndrome, depression, and anxiety. The most important step to manage this condition is lose at least 5% of body weight; therefore, having regular physical activity and fat free and zero-sugar meals are suggested to every woman having PCOS. Furthermore, taking alternative and complementary healthcare approaches with other therapies have an advantage to reduce the symptoms. Medical professionals often prescribe insulin sensitizers, ovulation inducers, oral contraceptives and antiandrogen drugs^32,33. Currently, there is no medicine authorized by the U.S. Food and Drug Administration (USFDA) specifically approved for PCOS, and all prescribed medications are utilized in an off-label manner. Aside from the critical need for advancement in the discovery and manufacturing of novel chemical compounds and new drug discoveries, drug repurposing strategies could lead to the identification of newer drugs. These therapies include drug targeting diabetes such as pioglitazone, empagliflozin, sitagliptinand liraglutide as well as HMG (3-hydroxy-3-methyl-3-glutaryl-) coenzyme A reductase inhibitorssuch as atorvastatin, rosuvastatin and simvastatin and mucolytic drugs such as N-acetyl cysteine^34,35

CONCLUSION:

The PCOS is a complex condition that can have a significant impact on a woman's health and quality of life. Probiotics are beneficial bacteria that can help to rebalance the gut microbiome and reduce inflammation throughout the body. By improving digestion and supporting the immune system, probiotics may be able to alleviate some of the symptoms associated with PCOS, such as irregular periods, acne, and weight gain. Literature confirms that, PCOS may begin in the earliest phases of development and manifest clinically later stages of adolescence; microbiome screening and initial probiotic administration in early childhood and adolescents may be beneficial for managing PCOS symptoms. In conclusion, while there is potential for probiotics to play a role in PCOS management, more research is needed to establish specific recommendations regarding strains, dosages, and long-term effects. Probiotics should not be considered a standalone treatment for PCOS, and their use should be part of a comprehensive approach that includes lifestyle modifications, dietary changes, and, if necessary, medical interventions.

Figure: Role of probiotic supplements in the management of Poly Cystic Ovary Syndrome

Abbreviation:

PCOD: Poly Cystic Ovary Disease

PCOS: Poly Cystic Ovary Syndrome

USFDA: U.S. Food and Drug Administration

SCFAS: Short-Chain Fatty Acids

GABA: Gamma-Aminobutyric Acid

BMI: Body Mass Index

ACKNOWLEDGMENT:

Nil

Funding Statement:

This study received no external fundings.

Institutional Review Board Statement:

Not applicable

CONFLICTS OF INTEREST:

The authors declare no conflicts of interest

REFERENCES:

1. Witchel SF, Oberfield SE, Peña AS. Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment with Emphasis on Adolescent Girls. J Endocr Soc. 2019; Jun 14; 3(8): 1545-1573. doi: 10.1210/js.2019-00078.

2. Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016; Oct; 37(5): 467-520. doi: 10.1210/er.2015-1104.

3. Singh S, Pal N, Shubham S, Sarma DK, Verma V, Marotta F, Kumar M. Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. J Clin Med. 2023; Feb 11; 12(4): 1454. doi: 10.3390/jcm12041454.

4. Dennett CC, Simon J. The role of polycystic ovary syndrome in reproductive and metabolic health: overview and approaches for treatment. Diabetes Spectr. 2015; May; 28(2): 116-20. doi: 10.2337/diaspect.28.2.116.

5. Davis CD. The Gut Microbiome and Its Role in Obesity. Nutr Today. 2016; Jul-Aug; 51(4): 167-174. doi: 10.1097/NT.0000000000000167.

6. Amara AA, Shibl A. Role of Probiotics in health improvement, infection control and disease treatment and management. Saudi Pharm J. 2015; Apr; 23(2): 107-14. doi: 10.1016/j.jsps.2013.07.001.

7. Angoorani P, Ejtahed HS, EttehadMarvasti F, Taghavi M, Mohammadpour Ahranjani B, Hasani-Ranjbar S, Larijani B. The effects of probiotics, prebiotics, and synbiotics on polycystic ovarian syndrome: an overview of systematic reviews. Front Med (Lausanne). 2023; Jun 9; 10: 1141355. doi: 10.3389/fmed.2023.1141355.

8. Zhang YJ, Li S, Gan RY, Zhou T, Xu DP, Li HB. Impacts of gut bacteria on human health and diseases. Int J Mol Sci. 2015; Apr 2; 16(4): 7493-519. doi: 10.3390/ijms16047493.

9. Bell V, Ferrao J, Pimentel L, Pintado M, Fernandes T. One Health, Fermented Foods, and Gut Microbiota. Foods. 2018; Dec 3; 7(12): 195. doi: 10.3390/foods7120195.

10. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017; May 16; 474(11): 1823-1836. doi: 10.1042/BCJ20160510.

11. Veena Kirthika S, Jibi Paul, Senthil Selvam. P, Sathya Priya. V. Effect of Aerobic exercise and life style intervention among young women with Polycystic Ovary Syndrome. Research J. Pharm. and Tech. 2019; 12(9): 4269-4273. doi: 10.5958/0974-360X.2019.00734.0

12. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013; Jan; 6(1): 39-51. doi: 10.1177/1756283X12459294.

13. Mancin Stefano, Mazzoleni Beatrice. Probiotics as adjuvant therapy in the treatment of Allergic Rhinitis. Research Journal of Pharmacy and Technology. 2023; 16(5): 2393-8. doi: 10.52711/0974-360X.2023.00394

14. Chen Y, Xu J, Chen Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients. 2021; Jun 19; 13(6): 2099. doi: 10.3390/nu13062099.

15. Averina OV, Zorkina YA, Yunes RA, Kovtun AS, Ushakova VM, Morozova AY, Kostyuk GP, Danilenko VN, Chekhonin VP. Bacterial Metabolites of Human Gut Microbiota Correlating with Depression. Int J Mol Sci. 2020; Dec 3; 21(23): 9234. doi: 10.3390/ijms21239234.

16. Putri Ramadhani, Suharjono, IswinarnoDosoSaputro, Ria Fitrah Arfiani, UlfaSyafli Nosa. Scoping Review: Effects of Probiotics against The Immune System in Burn patients. Research Journal of Pharmacy and Technology 2023; 16(1): 345-3. doi: 10.52711/0974-360X.2023.00061

17. Orisaka M, Mizutani T, Miyazaki Y, Shirafuji A, Tamamura C, Fujita M, Tsuyoshi H, Yoshida Y. Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging. Front Endocrinol (Lausanne). 2023; Dec 13; 14: 1324429. doi: 10.3389/fendo.2023.1324429.

18. Iif Hanifa Nurrosyidah, Ni Made Mertaniasih, IsnaeniIsnaeni. Antibacterial Activity of Probiotics Cell-Free Fermentation Filtrate from Passiflora edulis Sims. againts Pathogen bacteria. Research Journal of Pharmacy and Technology 2022; 15(12): 5767-3. doi: 10.52711/0974-360X.2022.00973

19. González F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012; Mar 10; 77(4): 300-5. doi: 10.1016/j.steroids.2011.12.003.

20. Zeber-Lubecka N, Ciebiera M, Hennig EE. Polycystic Ovary Syndrome and Oxidative Stress-From Bench to Bedside. Int J Mol Sci. 2023; Sep 15; 24(18): 14126. doi: 10.3390/ijms241814126.

21. Calcaterra V, Rossi V, Massini G, Casini F, Zuccotti G, Fabiano V. Probiotics and Polycystic Ovary Syndrome: A Perspective for Management in Adolescents with Obesity. Nutrients. 2023; Jul 14; 15(14): 3144. doi: 10.3390/nu15143144.

22. Le Barz M, Anhê FF, Varin TV, Desjardins Y, Levy E, Roy D, Urdaci MC, Marette A. Probiotics as Complementary Treatment for Metabolic Disorders. Diabetes Metab J. 2015; Aug; 39(4): 291-303. doi: 10.4093/dmj.2015.39.4.291.

23. Wissam Zam, Reine Dawod. Overview of the Probiotics’ role in Gastrointestinal disorders. Research J. Pharm. and Tech. 2020; 13(11): 5557-5561. doi: 10.5958/0974-360X.2020.00970.1

24. Tedelind S, Westberg F, Kjerrulf M, Vidal A. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World J Gastroenterol. 2007; May 28; 13(20): 2826-32. doi: 10.3748/wjg.v13.i20.2826.

25. Annette Babu, Ravichandran Veerasamy, Shalini Sivadasan. Metformin- A Drug of Plant Origin. Research J. Pharm. and Tech 2018; 11(6): 2701-2708. doi: 10.5958/0974-360X.2018.00499.7

26. Markowiak-Kopeć P, Śliżewska K. The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome. Nutrients. 2020; Apr 16; 12(4): 1107. doi: 10.3390/nu12041107.

27. Barber TM, Hanson P, Weickert MO, Franks S. Obesity and Polycystic Ovary Syndrome: Implications for Pathogenesis and Novel Management Strategies. Clin Med Insights Reprod Health. 2019; Sep 9; 13: 1179558119874042. doi: 10.1177/1179558119874042.

28. K.V. Swathi. Probiotics –A Human Friendly Bacteria. Research J. Pharm. and Tech. 2016; 9(8): 1260-1262. doi: 10.5958/0974-360X.2016.00239.0

29. Jalilian N, Haghnazari L, Rasolinia S. Leptin and body mass index in polycystic ovary syndrome. Indian J Endocrinol Metab. 2016; May-Jun; 20(3): 324-8. doi: 10.4103/2230-8210.180005.

30. Abhirup Dey, Mangala Lakshmi Ragavan, Sanjeeb Kumar Mandal, Nilanjana Das. Isolation, Identification and In vitro Characterisation of Probiotic Yeast Strains. Research J. Pharm. and Tech. 2017; 10(3): 726-732. doi: 10.5958/0974-360X.2017.00136.6

31. Den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D. J., and Bakker, B. M. (2013). The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research, 54(9), 2325–2340. https://doi.org/10.1194/jlr.R036012.

32. James, M., Varghese, T. P., Sharma, R., and Chand, S. (2020). Association Between Metabolic Syndrome and Diabetes Mellitus According to International Diabetic Federation and National Cholesterol Education Program Adult Treatment Panel III Criteria: a Cross-sectional Study. Journal of diabetes and metabolic disorders, 19(1), 437–443. https://doi.org/10.1007/s40200-020-00523-2

33. Md Kamal Hossain, Kamrun Nahar, Parisa Shokryazdan, Norhani Abdullah, Kaiser Hamid, Mohammed Faseleh Jahromi. Probiotic Potential of Lactic Acid Bacteria Isolated from Cheese, Yogurt and Poultry Faeces. Research J. Pharm. and Tech. 2017; 10(9): 2991-2998. doi: 10.5958/0974-360X.2017.00530.3.

34. Wittich, C. M., Burkle, C. M., and Lanier, W. L. (2012). Ten common questions (and their answers) about off-label drug use. Mayo Clinic proceedings, 87(10), 982–990. https://doi.org/10.1016/j.mayocp.2012.04.017

35. Wissam Zam, Reine Dawod. Overview of the Probiotics’ role in Gastrointestinal disorders. Research J. Pharm. and Tech. 2020; 13(11): 5557-5561. doi: 10.5958/0974-360X.2020.00970.1

Received on 14.12.2023 Revised on 04.04.2024

Accepted on 18.06.2024 Published on 24.12.2024

Available online from December 27, 2024

Research J. Pharmacy and Technology. 2024;17(12):6015-6019.

DOI: 10.52711/0974-360X.2024.00913