Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues.

The objective of the present study was to review the existing data on the association between Zn status and characteristics of gut microbiota in various organisms and the potential role of Zn-induced microbiota in modulating systemic effects. The existing data demonstrate a tight relationship between Zn metabolism and gut microbiota as demonstrated in Zn deficiency, supplementation, and toxicity studies. Generally, Zn was found to be a significant factor for gut bacteria biodiversity. The effects of physiological and nutritional Zn doses also result in improved gut wall integrity, thus contributing to reduced translocation of bacteria and gut microbiome metabolites into the systemic circulation. In contrast, Zn overexposure induced substantial alterations in gut microbiota. In parallel with intestinal effects, systemic effects of Zn-induced gut microbiota modulation may include systemic inflammation and acute pancreatitis, autism spectrum disorder and attention deficit hyperactivity disorder, as well as fetal alcohol syndrome and obesity. In view of both Zn and gut microbiota, as well as their interaction in the regulation of the physiological functions of the host organism, addressing these targets through the use of Zn-enriched probiotics may be considered an effective strategy for health management.

Serum, Whole Blood, Hair, and Mucosal Essential Trace Element and Mineral Levels in Children with Verified Chronic Rhinosinusitis Undergoing Functional Endoscopic Sinus Surgery.

The objective of the present study was to assess hair, serum, whole blood, and excised tissue essential element content in children with chronic rhinosinusitis (CRS). Eighty-eight children with chronic rhinosinusitis and 66 healthy controls were enrolled in the present study. Evaluation of endoscopic Lund-Kennedy and computed tomography Lund-Mackay scores, as well as tissue sampling, was performed only in children with chronic rhinosinusitis. Assessment of Sino-Nasal Outcome Test-20 (SNOT-20) scores was performed in both cases and controls. Hair, whole blood, blood serum, and excised mucosal tissue (only in patients) analysis was performed using inductively coupled argon plasma mass-spectrometry. The obtained data demonstrate that whole blood Ca, Mg, Se, and Zn, as well as hair Ca, Cu, Mg, and Zn levels in the examined patients were significantly lower as compared with the control values. Only serum Zn concentration in children with CRS exceeded the respective control values, whereas serum Cu levels only tended to decrease in CRS. In turn, hair Fe content in children with CRS exceeded that in healthy controls. Regression analysis demonstrate that hair Ca levels, as well as whole blood Ca, Se, and Zn concentrations, were considered as negative predictors, whereas increased hair iron level was significantly directly associated with CRS. Significant associations between hair, serum, whole blood, and tissue element levels and Lund-Kennedy and Lund-Mackay scores were also revealed. Generally, the obtained data demonstrate that chronic rhinosinusitis is associated with impaired essential metal levels in pediatric patients with chronic rhinosinusitis. The observed alterations may contribute to CRS pathogenesis through modulation of mucociliary clearance, immunity, inflammatory response, and redox environment.

A follow-up study of mucociliary clearance and trace element and mineral status in children with chronic rhinosinusitis before and three months after endoscopic sinus surgery.

BACKGROUND: The existing data demonstrate the potential role of trace elements in nasal mucociliary clearance, although the association between trace element and mineral status and ciliary function in children with chronic rhinosinusitis is insufficiently studied. Therefore, the objective of the present study is evaluation of trace element and mineral status and mucociliary function in pediatric CRS patients before and after functional endoscopic sinus surgery. METHODS: The present study involved 30 children with chronic rhinosinusitis without nasal polyps. During this follow-up the patients were examined preoperatively (point 0), underwent functional endoscopic sinus surgery, and were repeatedly examined at three months postoperatively (point 1). At both points the patients were subjected to quality-of-life assessment using SNOT-20 questionnaire; endoscopic and computer tomography examination of the nasal sinuses; evaluation of ciliary function and mucosal cytology using high-speed videomicroscopy; assessment of blood count and inflammatory markers; as well as analysis of trace element and mineral levels in whole blood, serum, and hair using inductively-coupled plasma mass-spectrometry. RESULTS: The obtained data demonstrate that endoscopic sinus surgery significantly improved sinonasal pathology in children with chronic rhinosinusitis, as evidenced by significantly reduced Lund-Mackay, Lund-Kennedy, and SNOT-20 scores. At the same time, no significant improvement of ciliary functions or mucosal cytology was observed postoperatively. Trace element status assessment demonstrated that postoperative serum Zn, whole blood Mg and Cu were significantly lower as compared to preoperative values. In contrast, serum Mn and Cr, as well as whole blood Cr and hair Se were characterized by a significant increase at three months postoperatively. Multiple linear regression analysis demonstrated that serum Zn is significantly associated with the number of ciliated cells and cell viability, whereas serum Mn and whole blood Cu concentrations are inversely associated with cell viability and ciliary length, respectively. Hair Se was found to be associated with the number of neutrophils in the mucosa biopsy. CONCLUSION: Redistribution of trace elements and minerals may at least partially mediate prolonged recovery of mucosal ciliary function in children with chronic rhinosinusitis in three months after functional sinus surgery, although the particular mechanisms of these alterations in trace element levels are to be discovered.

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for COronaVIrus Disease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

Zinc and respiratory tract infections: Perspectives for COVID­19 (Review).

In view of the emerging COVID­19 pandemic caused by SARS­CoV­2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID­19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS­CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin­converting enzyme 2 (ACE2), known to be the receptor for SARS­CoV­2. Improved antiviral immunity by zinc may also occur through up­regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti­inflammatory activity by inhibiting NF­κB signaling and modulation of regulatory T­cell functions that may limit the cytokine storm in COVID­19. Improved Zn status may also reduce the risk of bacterial co­infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID­19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID­19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator­induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.

Mucociliary transport as a link between chronic rhinosinusitis and trace element dysbalance.

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.