Exploring the impact of nanomembrane-based low volume plasma exchange on gut barrier integrity in metabolic syndrome: a prospective study
Authors: Slavic V. 
Published: February 2025

A comprehensive understanding of the human intestine and its structural-functional unit, the “gut barrier,” implies an intricate cross-talk between epithelial cells and the underlying immune system to coordinate the surveillance of intestinal luminal contents. Disruption of this barrier leads to an increased passage of antigens and macromolecules from the external environment into the host, triggering local or systemic inflammation and immune activation, commonly referred to as “leaky gut.” In recent times, increased intestinal permeability has been recognized as a key factor or pivotal pathogenic component in chronic inflammatory diseases, including metabolic disorders. Metabolic syndrome (MetSy) encompasses a cluster of metabolic disorders associated with an elevated risk of cardiovascular diseases, despite lifestyle modifications and medications. Zonulin, among the non-invasive markers of intestinal permeability, stands out due to its sensitivity. Nanomembrane-based low-volume plasma exchange (LVPE) is an innovative approach to blood purification designed to remove toxic and inflammatory blood components. This safe and minimally invasive procedure involves a device that pumps and filters the patient’s blood through nanopores in a multi-membrane layout. Objective. This study aims to investigate the impact of nanomembrane-based LVPE on the intestinal barrier in individuals with MetSy, elucidating its potential therapeutic role in chronic inflammatory diseases. Materials and methods. In this prospective study, 48 outpatient participants (31.3 % female, 68.7 % male) with an average age of 50 years underwent four cycles of nanomembrane-based LVPE, conducted every other day. Each cycle involved the removal of 30 % of circulating plasma, replaced with a saline solution. Serum samples were collected before the first and after the fourth LVPE cycle, measuring markers including Zonulin, C-reactive protein (CRP), high-sensitive CRP, Interleukin-6 (IL6), vitamin D3, and cardiometabolic parameters. Additionally, these markers were measured in plasma samples obtained after each LVPE cycle. Results. After four cycles of LVPE, there was a significant decrease in the concentrations of vitamin D3 (p < 0.001), CRP (p < 0.02), glucose (p < 0.0001), total cholesterol (p < 0.0001), triglycerides (p < 0.011), and HDL-C (p < 0.006). Before the first cycle, Zonulin was significantly associated with HDL-C (β = 1.406; p = 0.002), LDL-C (β = -1.263; p = 0.012), and hsCRP (β = 0.302; p = 0.046). After the fourth cycle, significant associations were obtained for HbA1c (β = 0.342; p = 0.025) and total cholesterol (β=0.570; p=0.001). Conclusion. Our study advocates for the use of nanomembrane-based LVPE as a targeted method to enhance gut barrier permeability in individuals with MetSy. Through four LVPE cycles, our research validates the efficacy of this approach in correcting carbohydrate and lipid metabolism. Notably, our investigation reveals LVPE’s potential immunomodulatory effect on inflammatory pathways.