The role of Demodex brevis and Demodex folliculorum in pathogenesis of demodicosis patients and the evaluation of intestinal permeability with serum zonulin level

Introduction and Aim: Demodex spp. are among the most common ectoparasites found on human skin. Under conditions of immunosuppression, their numbers can increase significantly, leading to an inflammatory skin disorder known as demodicosis. In recent years, it has become evident that the pathogenesis of inflammatory skin diseases may involve not only local factors but also systemic mechanisms. Increased intestinal permeability has emerged as a notable factor in this context. Zonulin is a protein secreted by enterocytes that regulates tight junctions between intestinal epithelial cells. Elevated zonulin levels are considered an important biomarker indicating disruption of the intestinal barrier and increased permeability. Accordingly, this study aimed to investigate the relationship between the density of Demodex folliculorum and Demodex brevis and serum zonulin levels in individuals diagnosed with demodicosis, to evaluate the potential link between cutaneous inflammation and intestinal barrier dysfunction. Materials and Methods: A total of 44 patients diagnosed with demodicosis and 41 age- and sex-matched healthy controls, all of whom presented to the Dermatology Outpatient Clinic of Düzce University, were included in the study. Participants' demographic characteristics, lifestyle habits, and pet ownership were recorded. The presence of Demodex folliculorum and Demodex brevis was determined using the standardized skin surface biopsy (SSSB) technique. Serum zonulin levels were measured spectrophotometrically using the ELISA method. The relationship between zonulin levels and Demodex species density was analyzed, and intergroup comparisons were performed using the Student's t-test and Fisher's exact test. Results: Mean serum zonulin levels were 25.34 ± 5.82 ng/ml in the patient group and 20.48 ± 7.59 ng/ml in the control group, with the difference being statistically significant (p=0.001). The rate of D. brevis positivity in the patient group was 36.4%, consistent with previous literature. No significant difference iv was found between D. brevis positivity and zonulin levels (p=0.971). When stratified by sex, female patients had significantly higher zonulin levels (25.31 ± 5.53 ng/ml) compared to male patients (18.97 ± 7.86 ng/ml, p<0.001). Clinically, patients with seborrhea had higher zonulin levels than those without (28.82 ± 4.01 ng/ml vs. 24.45 ± 5.92 ng/ml; p=0.043). Similarly, patients with acne had significantly elevated zonulin levels (30.24 ± 4.47 ng/ml) compared to those without (24.41 ± 5.62 ng/ml; p=0.014). Furthermore, pet ownership was significantly more common in patients with acne (71.4%) than in those without (18.9%) (p=0.011). No significant association was observed between zonulin levels and skincare or makeup habits. Conclusion: This study demonstrated that serum zonulin levels were significantly higher in patients with demodicosis compared to healthy individuals, suggesting a potential increase in intestinal permeability, particularly among those presenting with complaints of acne and seborrhea. Conversely, zonulin levels did not appear to be directly associated with the presence of Demodex brevis. These findings indicate that intestinal permeability may be elevated in patients with demodicosis; however, further large-scale studies are warranted to substantiate this association more robustly. Keywords: Demodicosis, Demodex, zonulin, intestinal permeability, biomarker