Metformin effects on zonulin level in polycystic ovarian women

Abstract

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. 

The Potential Relationship between Gastric and Small Intestinal-Derived Endotoxin on Serum Testosterone in Men

“…Additionally, the zonulin concentration values of 18 participants in this cohort were unintelligible, reducing the statistical power of this study. Considering that Metformin, a glucose-mediating medication used to manage type II diabetes, has been shown to augment intestinal microbial composition and T levels in women with PCOS, differences in the study population mean BMI (30.2 versus 25.6), and thereby glucose uptake and insulin-sensitivity (unmeasured in both studies), may further explain this discrepancy [66,67]. Supporting this notion of metabolic stress, namely inflammatory mechanical and metabolic stress-states occurring with high-intensity exercise and long periods of exercise, have been shown to increase intestinal permeability (as measured by zonulin) via alterations to intestinal microflora and reductions of gastrointestinal blood flow.…”