Serum zonulin level is not elevated in patients with polycystic ovary syndrome without metabolic syndrome

Çetin, Zeynep; Kösem, Arzu; Canbaz, Bülent; Baser, Ozden Ozdemir; Çatak, Merve; Turhan, Turan; Berker, Dilek

doi:10.1007/s00404-019-05345-z

Cited by 9 publications

(11 citation statements)

References 16 publications

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“…However, the first group of those of initial (HOMA-IR <2) exhibited no changes in zonulin value as there is no difference in gut permeability and microbiota composition before and after treatment, as non-insulin resistance associated with no alteration in intestinal permeability. This agrees to a certain degree with Cetin's study conclusion, who included non-obese, normal HOMA-IR PCOS patients in his study and suggested that insulin resistance is not triggered if there is integrity in the gut permeability [34]. It seems that this study is the first study to show the effect of metformin on zonulin in PCOS patients.…”

Section: Resultssupporting

confidence: 91%

Metformin effects on zonulin level in polycystic ovarian women

Ibrahim

Ahmeid

2020

ADMET DMPK

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Zonulin protein is a haptoglobin precursor and functions to modulate the permeability of tight junctions between enterocytes. Local inflammation or systemic inflammation can trigger zonulin expression. While the increased zonulin level causes an increase of intestinal permeability and entrance of foreign antigens, the latter can increase insulin resistance and inflammation. Polycystic ovarian syndrome affects women during their reproductive age characterized by hyperinsulinemia and/or hyperandrogenemia and associated with infertility problems. Changes in gut permeability such as irritable bowel syndrome are often found in PCOS patients. While metformin increases insulin mediates glucose uptake and, acts as an insulin-sensitizing drug used to treat PCOS patients is recently discovered to reshape intestinal bacteria and hence may affect intestinal action. This study was designed to find any association between zonulin level and other parameters in PCOS patients and to find metformin treatment effects on zonulin in PCOS patients. Thirty-one newly diagnosed PCOS women agree to take metformin 850 mg twice daily for three months and, and to give fasting serum samples to measure zonulin, FSH, LH, total testosterone, free testosterone, SHBG, fasting insulin, and fasting serum glucose before and after treatment. The free testosterone and zonulin are determined by the ELISA technique while the other parameters are determined by the Cobas technique. According to patients’ Homeostatic Model Assessment (HOMA-IR), the Patients were divided into two sub-groups: the first group consisting of those with initial HOMA-IR less than two and the second group was those of an initial HOMA-IR of between two to four. Whereas the first group showed no significant response to treatment, the second group showed a better response to metformin treatment, as demonstrated by their LH, total testosterone, free testosterone, fasting insulin, zonulin, and glucose levels. These parameters markedly improved after metformin treatment with p-values of 0.08, 0.09, 0.07. 0.04, 0.01 and 0.06, respectively.

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Section: Resultssupporting

confidence: 91%

Metformin effects on zonulin level in polycystic ovarian women

Ibrahim

Ahmeid

2020

ADMET DMPK

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“…There are contradictory reports on the link between gut barrier markers and PCOS. While Zhang et al (2015) [79] and Lindheim et al (2017) [4] reported that zonulin and LBP were increased in PCOS patients, Zeynep et al (2019) [80] reported the opposite. In comparison to these reports, our L group did not show any significant changes in claudin-2 and occludin expression.…”

Section: Discussionmentioning

confidence: 98%

Effects of Soy Isoflavones, Resistant Starch and Antibiotics on Polycystic Ovary Syndrome (PCOS)-Like Features in Letrozole-Treated Rats

et al. 2021

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Recently, various dietary interventions have been used extensively as a novel therapy against PCOS. In the present study, we show that soy isoflavone metabolites and resistant starch, together with gut microbiota modulations, were successful in decreasing the severity of PCOS-like reproductive features while increasing the expression of gut barrier markers and butyric acid in the gut. In the letrozole-induced PCOS model rats, the intake of both 0.05% soy isoflavones and 11% resistant starch, even with letrozole treatment, reduced the severity of menstrual irregularity and polycystic ovaries with a high concentration of soy isoflavones and equol in plasma. Antibiotic cocktail treatment suppressed soy isoflavone metabolism in the gut and showed no considerable effects on reducing the PCOS-like symptoms. The mRNA expression level of occludin significantly increased with soy isoflavone and resistant starch combined treatment. Bacterial genera such as Blautia, Dorea and Clostridium were positively correlated with menstrual irregularity under resistant starch intake. Moreover, the concentration of butyric acid was elevated by resistant starch intake. In conclusion, we propose that both dietary interventions and gut microbiota modulations could be effectively used in reducing the severity of PCOS reproductive features.

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“…In line with the present results, in one study, no differences in the levels of serum zonulin were reported in women with PCOS without metabolic syndrome, compared with controls. 35 In contrast, Zhang et al reported elevated levels of serum zonulin in women with PCOS compared with healthy Open access controls. 36 Of note, there were significant differences in the metabolic profiles of women with PCOS compared with the controls in their study, whereas in the present study metabolic profiles were comparable in the study groups.…”

Section: Discussionmentioning

confidence: 92%

“…Insulin resistance is a common feature in women with PCOS. 40 Few studies have examined the association of serum zonulin levels with insulin resistance, but the results have been conflicting; both no correlation 35 and a positive correlation 12 36 have been reported. In the present study, serum zonulin levels were correlated with HOMA-IR values in both women with PCOS and in controls after adjustment for BMI.…”

Section: Discussionmentioning

confidence: 99%

Markers of gastrointestinal permeability and dysbiosis in premenopausal women with PCOS: a case–control study

et al. 2021

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ObjectivesAltered intestinal permeability and gut barrier dysfunction have been suggested to play a role in the pathogenetic mechanism of polycystic ovary syndrome (PCOS), the most common endocrine and metabolic condition in reproductive-aged women. However, data on intestinal permeability and dysbiosis of the gut microbiota in PCOS is still limited, with conflicting results. To this end, the concentrations of gastrointestinal permeability and gut dysbiosis markers were analysed in women with PCOS.DesignCase–control study.SettingGeneral community.Participants104 women with PCOS and 203 body mass index (BMI) matched control women at age 46.Primary and secondary outcome measuresSerum levels of zonulin, fatty acid-binding protein 2 (FABP2), urinary levels of indican, and hormonal and metabolic parameters.ResultsSerum levels of zonulin (128.0±17.0 vs 130.9±14.0 ng/mL, p=0.13) and FABP2 (1.5±0.9 vs 1.5±0.7 ng/mL, p=0.63) and urinary levels of indican (9.5±5.5 vs 8.4±4.2 mg/dL, p=0.07) were comparable in women with PCOS and controls in the whole study population. Likewise, when the study population was divided into different BMI groups as normal weight, overweight and obese, the levels of the above markers were comparable between the study groups. After BMI adjustment, zonulin levels correlated with the levels of high-sensitivity C reactive protein and homoeostasis model assessment of insulin resistance (p<0.05) both in women with PCOS and controls.ConclusionsIntestinal permeability markers zonulin and FABP2, and the dysbiosis marker indican do not seem to be altered in women with PCOS at age 46 compared with BMI-matched controls. Serum zonulin levels correlated with BMI, insulin resistance and inflammatory marker levels, but did not segregate women with PCOS and controls. This suggests that metabolic factors, but not PCOS per se, is the driving force of dysbiosis in premenopausal women with PCOS.

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Serum zonulin level is not elevated in patients with polycystic ovary syndrome without metabolic syndrome

Cited by 9 publications

References 16 publications

Metformin effects on zonulin level in polycystic ovarian women

Metformin effects on zonulin level in polycystic ovarian women

Effects of Soy Isoflavones, Resistant Starch and Antibiotics on Polycystic Ovary Syndrome (PCOS)-Like Features in Letrozole-Treated Rats

Markers of gastrointestinal permeability and dysbiosis in premenopausal women with PCOS: a case–control study

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