Probiotics for Children with Asthma?

    probiotics microflora

    Leading to nearly one-half million deaths worldwide in 2019, asthma is a major non-communicable disease in all age groups. It is the most common chronic disease among children. Many factors have been linked to an increased risk of children developing asthma, although it is often difficult to find a single, direct cause.

    Gut and lung microbiota present as relevant influences. Increased prevalence of asthma has been linked to reduced exposure to substances that promote immune system maturation. Because the maturation of innate and acquired immunity occurs mainly at the gut level, gut microbes are thought to play an important role in what is termed the “hygiene hypothesis.”

    Recent research suggests a role for probiotics in rebalancing immune response, repairing dysbiosis, and mitigating airway inflammation in asthma.

    Asthma, in brief

    Asthma is a condition marked by chronic inflammation of the respiratory tract, reversible airflow limitation, and bronchial hyper-reactivity.

    Inflammation and narrowing of the small airways in the lungs cause asthma symptoms, which can be any combination of cough, wheeze, shortness of breath, and chest tightness. Asthma symptoms can be made worse by common triggers: viral infections (colds), dust, smoke, fumes, changes in the weather, grass and tree pollen, animal fur and feathers, strong soaps, and perfume.

    Factors linked to an increased risk of developing asthma include family incidence, having other allergic conditions, early life events (low birth weight, prematurity, exposure to tobacco smoke and other sources of air pollution, as well as viral respiratory infections), overweight and obesity, and exposure to a range of environmental allergens and irritants (house dust mites, molds, and occupational exposure to chemicals, fumes or dust.)

    Asthma cannot be cured, but good management with inhaled medications (bronchodilators and/or steroids) can control the disease. In addition, biologics, such as blocking mediators of inflammation, may be indicated for severe asthma. However, access to these treatments is often limited in many low- and low-middle-income countries.

    Rationale for probiotics in childhood asthma

    The aforementioned “hygiene hypothesis” emerged because of the observation that allergic diseases such as asthma were more prevalent in affluent populations than in people exposed to less hygienic settings. Natural environments enrich the human microbiome, promote immune balance, and protect from allergy and inflammatory disorders. A decline in biodiversity may disturb the immune response and microbial balance.

    Asthmatic children may present with dysbiosis of the intestinal and respiratory microbiome. Dysbiosis may promote the start of inflammatory pathways and pitch in bronchial obstruction and airway hyper-reactivity. Moreover, intestinal dysbiosis significantly affects asthma pathogenesis.

    Commonly used drugs such as antibiotics may imbalance gut and lung microbiota. The dysregulation of the gut-lung axis contributes to allergic disorders.

    Potential mechanisms of action by probiotics in asthma

    Oral probiotics may be beneficial through various actions

    • Fortifying intestinal barrier
    • Inhibiting the growth of pathogens
    • Activating mucosal and innate immunity
    • Activating anti-inflammatory processes

    Reviews and meta-analyses of probiotics in asthma 

    Systematic reviews and meta-analyses of probiotics in asthma and allergic diseases have been conducted with various conclusions. Some observed no benefit while others saw benefits with specific strains. Therefore, analyzing the data concerning a single probiotic strain is necessary. Each strain may exert specific activities depending on its unique characteristics.

    Individual studies with probiotics

    The following double-blinded, placebo-controlled studies reported on specific probiotic products.

    • Fermented milk containing Lacticaseibacillus casei:  a study in 187 asthmatic preschoolers for one-year showed no effect.
    • Lacticaseibacillus rhamnosus supplementation: a study in 131 at-risk infants for six months showed a reduced number of sensitizations both after six months and a further 6-month follow-up.
    • Lactobacillus gasseri supplementation: a study for eight weeks in 105 asthmatic children reported enhanced bronchial function and diminished asthma.
    • Limosilactobacillus reuteri supplementation: a study in 50 asthmatic children for two months showed dampened type-2 inflammation.
    • A probiotic mixture containing specific strains of Bifidobacterium longum,  Bifidobacterium infantis, and Bifidobacterium breve: a study in 40 children with seasonal allergic rhinitis and intermittent asthma for four weeks observed reduced respiratory symptoms and improved quality of life.
    • A multi-strain synbiotic containing Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus delbrueckii subsp. bulgaricus, and fructooligosaccharides: a study in 72 asthmatic children for 60 days reported reduced viral respiratory infections, but only during the first month.
    • A synbiotic compound containing Bifidobacterium infantis and fructooligosaccharides: a study in asthmatic children for six months reported a significant reduction in outpatient visits for asthma-related problems.
    • A probiotic mixture containing specific strains of Ligilactobacillus salivarius and Bifidobacterium breve: Probiotics in Pediatric Asthma Management (PROPAM):  study for 16 weeks in 446 children with asthma or wheezing reported that the probiotic mixture diminished the odds of having an acute respiratory episode to a third. The probiotic mixture reduced nearly a quarter of the likelihood of having two crises and halved the number of children with moderate to severe attacks.

    In summary, these studies show considerable evidence that probiotic supplementation reduced asthma severity in children with pre-existing asthma.

    Prevention has been less successful. A meta-analysis of 11 clinical trials concluded that probiotics supplementation in the first months after birth did not decrease the risk of asthma development in the first years of life in high-risk children.

    Some findings do support the possibility that prenatal probiotics supplementation may prevent allergies and asthma, mostly in children at high risk of allergy development. However, the grade of evidence is still slight, and further studies are needed.

    Takeaway

    Based on the existing literature, oral probiotics may be beneficial in children with asthma. However, the duration of treatments, entities evaluated, strains used, and characteristics of enrolled subjects varied across studies. The choice of probiotics (strain-specific) should be based on documented evidence.

    Key References

    Ahanchian, Hamid et al. “A multi-strain Synbiotic may reduce viral respiratory infections in asthmatic children: a randomized controlled trial.” Electronic physician vol. 8,9 2833-2839. 20 Sep. 2016, doi:10.19082/2833

    Chen, Yue-Sheng et al. “Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis.” Pediatric pulmonology vol. 45,11 (2010): 1111-20. doi:10.1002/ppul.21296

    Chiu, Chiao-Juno, and Miao-Tzu Huang. “Asthma in the Precision Medicine Era: Biologics and Probiotics.” International journal of molecular sciences vol. 22,9 4528. 26 Apr. 2021, doi:10.3390/ijms22094528

    Ciprandi, Giorgio, and Maria Angela Tosca. “Probiotics in Children with Asthma.” Children (Basel, Switzerland) vol. 9,7 978. 29 Jun. 2022, doi:10.3390/children9070978

    Colquitt, Alexander S et al. “Do Probiotics in Pregnancy Reduce Allergies and Asthma in Infancy and Childhood? A Systematic Review.” Nutrients vol. 14,9 1852. 28 Apr. 2022, doi:10.3390/nu14091852

    Fiuza, Bianca Sampaio Dotto et al. “Understanding Asthma and Allergies by the Lens of Biodiversity and Epigenetic Changes.” Frontiers in immunology vol. 12 623737. 1 Mar. 2021, doi:10.3389/fimmu.2021.623737

    Giovannini, Marcello et al. “A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis.” Pediatric research vol. 62,2 (2007): 215-20. doi:10.1203/PDR.0b013e3180a76d94

    Hassanzad, Maryam et al. “Synbiotics and Treatment of Asthma: A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial.” Galen medical journal vol. 8 e1350. 28 Jun. 2019, doi:10.31661/gmj.v8i0.1350

    Hufnagl, Karin et al. “Dysbiosis of the gut and lung microbiome has a role in asthma.” Seminars in immunopathology vol. 42,1 (2020): 75-93. doi:10.1007/s00281-019-00775-y

    Kang, Y B et al. “Gut microbiota and allergy/asthma: From pathogenesis to new therapeutic strategies.” Allergologia et immunopathologia vol. 45,3 (2017): 305-309. doi:10.1016/j.aller.2016.08.004

    Maldonado Galdeano, Carolina et al. “Beneficial Effects of Probiotic Consumption on the Immune System.” Annals of nutrition & metabolism vol. 74,2 (2019): 115-124. doi:10.1159/000496426

    Miraglia Del Giudice, M et al. “Airways allergic inflammation and L. reuterii treatment in asthmatic children.” Journal of biological regulators and homeostatic agents vol. 26,1 Suppl (2012): S35-40.

    Miraglia Del Giudice, Michele et al. “Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma.” Italian journal of pediatrics vol. 43,1 25. 7 Mar. 2017, doi:10.1186/s13052-017-0340-5

    Pfefferle, Petra I et al. “The Hygiene Hypothesis – Learning From but Not Living in the Past.” Frontiers in immunology vol. 12 635935. 16 Mar. 2021, doi:10.3389/fimmu.2021.635935

    Platts-Mills, Thomas A E. “The allergy epidemics: 1870-2010.” The Journal of allergy and clinical immunology vol. 136,1 (2015): 3-13. doi:10.1016/j.jaci.2015.03.048

    Rose, M A et al. “Efficacy of probiotic Lactobacillus GG on allergic sensitization and asthma in infants at risk.” Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology vol. 40,9 (2010): 1398-405. doi:10.1111/j.1365-2222.2010.03560.x

    Strachan, D P. “Hay fever, hygiene, and household size.” BMJ (Clinical research ed.) vol. 299,6710 (1989): 1259-60. doi:10.1136/bmj.299.6710.1259

    von Mutius, Erika. “The “Hygiene Hypothesis” and the Lessons Learnt From Farm Studies.” Frontiers in immunology vol. 12 635522. 18 Mar. 2021, doi:10.3389/fimmu.2021.635522

    Wawryk-Gawda, Ewelina et al. “Postnatal probiotics administration does not prevent asthma in children, but using prebiotics or synbiotics may be the effective potential strategies to decrease the frequency of asthma in high-risk children – a meta-analysis of clinical trials.” Allergologia et immunopathologia vol. 49,4 4-14. 1 Jul. 2021, doi:10.15586/aei.v49i4.69

    Authorship

    Clare Fleishman, MS, RDN, bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media, and websites. In 2010, she launched www.ProbioticsNow.com to share the cascade of discoveries in the microbiome. Always amazed at this “forgotten organ” Fleishman also creates white papers, blogs, videos, and social media for the International Probiotics Association. In 2022, she published a book titled Fertility: Why Microbes, Weight & Nutrition Matter.

    The International Probiotics Association (IPA) is a global non-profit organization bringing together through its membership, the probiotic sector’s stakeholders including but not limited to academia, scientists, health care professionals, consumers, industry, and regulators. The IPA’s mission is to promote the safe and efficacious use of probiotics throughout the world. Holding NGO status before Codex Alimentarius, the IPA is also recognized as the unified “Global Voice of Probiotics” around the world.

    IPA disclaimer: Probiotics have different characteristics, qualities and actions that are unique to the specific strain or combinations. The label should identify the genus, species and strain for each microorganism in the product (i.e. Lactobacillus acidophilus IPA001). If a claim pertaining to individual strains or a blend of strains contained in the product is made, the manufacturer should maintain evidence that the amount(s) provided in the product is consistent with the scientific evidence in support of the claim.