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Zinc and Bacillus clausii: a promising combination to improve immunity in children?

EFSM: 2022;2:220084DOI: 10.52778/efsm.22.0084Publication date: 10.04.2022
Dorothea M. Greifenberg and Marcos Perez III.

Dietary administration of zinc and use of probiotics can strengthen the immune system in humans, including children. This may lead to fewer and shorter respiratory tract infection episodes. Whether the combination of zinc and probiotics exerts synergistic effects remains to be tested.

Respiratory tract infections are common in childhood. While they are mostly mild, they not only cause suffering of the children but also impact the life of the parents, for instance by forcing them to stay home and miss work. On the other hand, exposure to viruses that are not considered life-threatening helps develop the immune system, thereby strengthening its ability to deal with more dangerous infectious agents in later life. Nonetheless, shortening and weakening periods of acute infection in children is desirable because it alleviates suffering of children and mitigates its impact on the life of the parents. This holds particularly true with interventions to shorten and weaken acute infections, such as those of the respiratory tract, that do not target the viruses but rather strengthen the pediatric immune system.

An expert panel of the European Food Safety Agency has stated that a cause-effect relationship exists between the dietary intake of zinc and normal function of the immune system [2]. It found that zinc deficiency renders people more susceptible to infections, while zinc supplementation has shown benefit for immune responses to bacterial and viral infections including effects in humans, including infants. The role of Zinc as an antiviral can be divided into two categories: 1. zinc supplementation to improve the antiviral response and systemic immunity in patients with zinc deficiency and 2. zinc treatment to specifically inhibit viral replication or infection-related symptoms [3].

Another general factor regulating immunity is the intestinal microbiome which has a complex and dynamic relationship with the immune system. The observed symbiotic dialogue plays an important role in the induction, education and function of the immune system [4]. Therefore, treatment with probiotics can improve the immune status as highlighted in a recent review [7]. For instance, the probiotic Bacillus clausii has shown antimicrobial and immunomodulatory properties in multiple studies [5]. These appear to occur primarily in the gut and secondarily affect the overall immune function. Two studies in children with respiratory tract infections highlight these effects.

An initial study treated 10 allergic children with frequent upper respiratory infections attending a nursery school (mean age 4.4 years) for 4 weeks with a B. clausii preparation and evaluated its effects on various cytokines recovered from nasal lavage [1]. Treatment with B. clausii induced a biologically relevant and statistically significant decrease of IL-4 levels, and a significant increase of IFN-γ, IL-12, TGF-β, and IL-10 levels. These data suggested that oral treatment with B. clausii may exert immunomodulating activity by affecting the cytokine pattern at the nasal level in allergic children with recurrent respiratory infections.

To test the clinical relevance of such findings, a later study randomized 80 children (mean age 4.3 years; 37 known to be atopic) to receive B. clausii for 3 months or to be in the control group in a single-blind design with an additional 3 months of follow-up [6]. During the treatment period, children receiving B. clausii had fewer respiratory infections with a shorter duration (Fig. 1). Similar data were observed in the follow-up period and in the group of children with allergies.

In conclusion, evidence shows that dietary intake of zinc and administration of probiotics such as B. clausii can strengthen the developing immune system to reduce and shorten acute infections. Whether their combination exerts synergistic effects remains to be studied.


  1. Ciprandi G, Tosca MA, Milanese M, Caligo G, Ricca V. Cytokines evaluation in nasal lavage of allergic children after Bacillus clausii administration: A pilot study. Pediatric Allergy and Immunology 2004;15:148–51.
  2. EFSA Panel on Dietetic Products N, Allergies. Scientific Opinion on the substantiation of health claims related to zinc and function of the immune system (ID 291, 1757), DNA synthesis and cell division (ID 292, 1759), protection of DNA, proteins and lipids from oxidative damage (ID 294, 1758), maintenance of bone (ID 295, 1756), cognitive function (ID 296), fertility and reproduction (ID 297, 300), reproductive development (ID 298), muscle function (ID 299), metabolism of fatty acids (ID 302), maintenance of joints (ID 305), function of the heart and blood vessels (ID 306), prostate function (ID 307), thyroid function (ID 308), acid-base metabolism (ID 360), vitamin A metabolism (ID 361) and maintenance of vision (ID 361) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 2009;7:1229.
  3. Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in antiviral immunity. Advances in Nutrition 2019;10(4):696–710,
  4. Belkaid Y, Harrison  OJ. Homeostatic immunity and the microbiota. Immunity 2017;46(4):562–576. doi: 10.1016/j.immuni.2017.04.008.
  5. Lopetuso LR, Scaldaferri F, Franceschi F, Gasbarrini A. Bacillus clausii and gut homeostasis: state of the art and future perspectives. Expert Review of Gastroenterology & Hepatology 2016;10:943–8.
  6. Marseglia GL, Tosca M, Cirillo I, Licari A, et al. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study. Therapeutics and Clinical Risk Management 2007;3:13–7.
  7. Wang X, Zhang P, Zhang X. Probiotics regulate gut microbiota: an effective method to improve immunity. Molecules 2021;26(19):6076.

Conflict of interest: D. M. Greifenberg and M. Perez III. are employees of Sanofi-Aventis.

Disclosures: Medical writing and publication funded by Sanofi-Aventis Deutschland GmbH.

Affiliation/Correspondence: Dorothea M. Greifenberg, PhD, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany and Marcos Perez III., MD, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, Frankfurt am Main, Germany
Submission date: 29.10.2021Acceptance date: 01.04.2022Publication date: 10.04.2022
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