BACKGROUND: ß-glucans isolated from natural sources have demonstrated pluripotent immunomodulatory potential, making them a promising supportive treatment for the management of recurrent respiratory infections (RRIs) in children. This study aimed to evaluate the effects of a pleuran-based supplement (ß-glucan isolated from Pleurotus ostreatus in combination with vitamin D and zinc) on mucosal immunity -through modulating salivary secretory immunoglobulin A (sIgA) levels -in children with RRIs. METHODS: This monocentric, prospective, open-label pilot study investigated the effect of an orally administered pleuran/vitamin D/zinc supplement (1-2 chewable tablets daily depending on body weight) on the dynamics of sIgA secretion measured in saliva samples collected at three timepoints: at baseline and after 4-6 and 8-10 days. RESULTS: This study included 49 children aged 6-11 years (mean age: 8.2 ± 1.6 years) with a history of one or more of the following conditions in the inclusion criteria: RRIs, allergy, and asthma. After 8-10 days with daily administration of the chewable pleuran/vitamin D/zinc supplement, children exhibited a statistically significant increase in salivary sIgA concentrations compared with baseline (227 ± 211 µg/mL; P = 0.045). No adverse events were observed during the course of the study in relation to the administration of pleuran-based supplement. CONCLUSIONS: We demonstrated the beneficial effects of the short-term administration of a pleuran-based chewable supplement on mucosal immunity through increasing salivatory sIgA levels. This study confirms the favourable safety profile of this pleuran/vitamin D/zinc combination, which could be beneficial for children with acute or recurrent respiratory infections, including children with allergies and/or asthma. Moreover, the significant increases in salivary sIgA concentrations that were observed after a few days of supplementation support the use of pleuran in not only the prevention but also the treatment of acute respiratory infections.

Clinic of Paediatric Respiratory Diseases and Tuberculosis National Institute of Paediatric Tuberculosis and Respiratory Diseases Dolny Smokovec Jessenius Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia

Department of Clinical Pharmacy and Pharmacology University of Groningen Groningen The Netherlands

Department of Microbial Genetics Institute of Molecular Biology Slovak Academy of Sciences Bratislava Slovakia

Department of Microbiology Faculty of Medicine Slovak Medical University Bratislava Slovakia

Department of Microbiology Immunology and Transplantation KU Leuven Catholic University of Leuven Leuven Belgium

Department of Pathological Physiology Jessenius Faculty of Medicine Comenius University in Bratislava University Teaching Hospital Martin Slovakia

Department of Pediatrics and Adolescent Medicine Jessenius Faculty of Medicine Comenius University in Bratislava University Teaching Hospital in Martin Martin Slovakia

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Institute of Clinical Immunology and Medical Genetics Jessenius Faculty of Medicine in Martin Comenius University in Bratislava University Hospital Martin Martin Slovakia

See more in PubMed

Chiappini E., Santamaria F., Marseglia G.L., et al. Prevention of recurrent respiratory infections : inter-society consensus. Ital. J. Pediatr. 2021;47:211. PubMed PMC

De Martino M., Ballotti S. The child with recurrent respiratory infections: normal or not? Pediatr. Allergy Immunol. 2007;18:13–18. PubMed

Cardinale F., La Torre F., Tricarico L.G., et al. Why do some children get sick with recurrent respiratory infections? Curr. Pediatr. Res. 2024;20:2003–2015. PubMed

Grammatico-Guillon L., Shea K., Jafarzadeh S.R., et al. Antibiotic prescribing in outpatient children: a cohort from a clinical data warehouse. Clin. Pediatr. (Phila.). 2019;58:681–690. PubMed

Kausar M.A., Rabie A.M., Azam F., et al. The role of Aedes aegypti in inducing/aggravating IgE-mediated allergic airway disease: extensive computational studies for identification of allergenic proteins. J. Biomol. Struct. Dyn. 2024;42:2738–2745. PubMed

Koenen M.H., van Montfrans J.M., Sanders E.A.M., et al. Immunoglobulin a deficiency in children, an undervalued clinical issue. Clin. Immunol. 2019 PubMed

Huus K.E., Petersen C., Finlay B.B. Diversity and dynamism of IgA-microbiota interactions. Nat. Rev. Immunol. 2021;21:514–525. PubMed

van Steenwijk H.P., Bast A., de Boer A. Immunomodulating effects of fungal beta-glucans: from traditional use to medicine. Nutrients. 2021;13:1333. PubMed PMC

Zhong X., Wang G., Li F., et al. Immunomodulatory effect and biological significance of β-glucans. Pharmaceutics. 2023;15:1615. PubMed PMC

Novak M., Vetvicka V. Beta-glucans, history, and the present: immunomodulatory aspects and mechanisms of action. J. Immunotoxicol. 2008;5:47–57. PubMed

Patidar A., Mahanty T., Raybarman C., et al. Barley beta-Glucan and Zymosan induce dectin-1 and Toll-like receptor 2 co-localization and anti-leishmanial immune response in Leishmania donovani-infected BALB/c mice. Scand. J. Immunol. 2020;92:e12952. PubMed

Su C.H., Lu M.K., Lu T.J., et al. A (1→6)-branched (1→4)-β-d-glucan from Grifola frondosa inhibits lipopolysaccharide-induced cytokine production in RAW264.7 macrophages by binding to TLR2 rather than dectin-1 or CR3 receptors. J. Nat. Prod. 2020;83:231–242. PubMed

Bindu S., Dandapat S., Manikandan R., et al. Prophylactic and therapeutic insights into trained immunity: a renewed concept of innate immune memory. Hum. Vaccin. Immunother. 2022;18 PubMed PMC

Ochando J., Mulder W.J.M., Madsen J.C., et al. Trained immunity - basic concepts and contributions to immunopathology. Nat. Rev. Nephrol. 2023;19:23–37. PubMed PMC

De Marco Castro E., Calder P.C., Roche H.M. β-1,3/1,6-glucans and immunity: state of the art and future directions. Mol. Nutr. Food Res. 2021;65 PubMed PMC

Murphy E.J., Rezoagli E., Major I., Rowan N.J. Laffey JG. β-glucan metabolic and immunomodulatory properties and potential for clinical application. J. Fungi. 2020;6:356. PubMed PMC

Wzorek-Łyczko K., Woźniak W., Piwowarczyk A., Kuchar E. The anti-infective effect of β-glucans in children. Int. J. Vitam. Nutr. Res. 2024;94:296–307. PubMed

Jesenak M., Majtan J., Rennerova Z., et al. Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Int. Immunopharmacol. 2013;15:395–399. PubMed

Rennerova Z., Picó Sirvent L., Carvajal Roca E., et al. Beta- (1,3/1,6)-d-glucan from Pleurotus ostreatus in the prevention of recurrent respiratory tract infections: an international, multicentre, open-label, prospective study. Front. Pediatr. 2022;10 PubMed PMC

Jesenak M., Hrubisko M., Majtan J., et al. Anti-allergic effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Phytother. Res. 2014;28:471–474. PubMed

Jesenak M., Hrubisko M., Chudek J., et al. EAACI Meeting 2023. Vol. 78. Allergy; 2023. Beneficial effect of β-glucan from Pleurotus ostreatus on clinical course and frequency of respiratory infections in children with persistent bronchial asthma –A double-blind placebo-controlled multicentre study (IMCCA study) p. 201.

Karacsonyi S., Kuniak L. Polysaccharides of Pleurotus ostreatus: isolation and structure of pleuran, an alkali-insoluble β-d-glucan. Carbohydr. Polym. 1994;24:107–111.

Drummond P.D., Hewson-Bower B. Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections. J. Psychosom. Res. 1997;43:271–278. PubMed

Timm T.G., Costa T.M., Alberton M.D., et al. Mushroom β-glucans: application and innovation for food industry and immunotherapy. Appl. Microbiol. Biotechnol. 2023;107:5035–5049. PubMed

Hassan A., Sada K.K., Ketheeswaran S., et al. Role of zinc in mucosal health and disease: a review of physiological, biochemical, and molecular processes. Cureus. 2020;12:e8197. PubMed PMC

Fakhoury H.M.A., Kvietys P.R., Kattan W., et al. Vitamin D and intestinal homeostasis: barrier, microbiota, and immune modulation. J. Steroid Biochem. Mol. Biol. 2020;200 PubMed

Richter J., Svozil V., Král V., et al. β-glucan affects mucosal immunity in children with chronic respiratory problems under physical stress: clinical trials. Ann. Transl. Med. 2015;3:52. PubMed PMC

Fuller R., Moore M.V., Lewith G., et al. Yeast-derived β-1,3/1,6 glucan, upper respiratory tract infection and innate immunity in older adults. Nutrition. 2017;39-40:30–35. PubMed

Lehne G., Haneberg B., Gaustad P., et al. Oral administration of a new soluble branched beta-1,3-d-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteers. Clin. Exp. Immunol. 2006;143:65–69. PubMed PMC

McFarlin B.K., Carpenter K.C., Davidson T., McFarlin M.A. Baker's yeast beta glucan supplementation increases salivary IgA and decreases cold/flu symptomatic days after intense exercise. J. Diet. Suppl. 2013;10:171–183. PubMed PMC

Muhammed H. Effect of vitamin D supplement on gingivitis and salivary parameters in patients with vitamin D deficiency. Al-Mustansiriyah J Sci. 2018;17:8.

Scott J., Kazman J., Palmer J., et al. Effects of vitamin D supplementation on salivary immune responses during Marine Corps basic training. Scand. J. Med. Sci. Sports. 2019;29:1322–1330. PubMed

Schlesinger L., Arevalo M., Arredondo S., et al. Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants. Am. J. Clin. Nutr. 1992;563:491–498. PubMed