Spring Fever Probiotics and Allergy Online
Spring Fever Probiotics and Allergy Online
Spring Fever Probiotics and Allergy Online
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Introduction
Allergies, although more frequently reported in childhood, affect all age groups and
impair the quality of life of 30-40% of people. Exposure to an allergen may give
rise to a hypersensitivity reaction caused by an immunological response to a specific
antigen acting on innate immune cells; repeated contact with an allergen triggers
the activation of mast cells and basophils and the release of allergic mediators.1
Consequent symptoms range from sneezing and itchy rashes to severe shortness
of breath and anaphylaxis. Alternatives to pharmacological treatment of allergic
The influence of oral diseases and for symptom reduction are desirable.1
probiotic administration
in allergy disease In the context of allergic disease, the gut microbiota modulates the immune system
limitation is now being via the production of molecules with immunomodulatory and anti-inflammatory
emphasised more functions that are capable of affecting immune cells. Gut dysbiosis, characterised by
regularly changes in the quantitative and qualitative composition of microbiota, may lead to
altered host-microbial interaction that can contribute to a disease state.1,2
by an unrestricted educational
grant from Cipla. The content
of the report is independent of
the sponsor.
Probiotics are one of many strategies that may have an effect on dysbiosis, altering the
perturbed intestinal microbiota with specific mechanisms of action that have not been
completely elucidated (Table 1). The influence of oral probiotic administration in allergy
disease limitation is now being emphasised more regularly.1-3
• Colonise and normalise perturbed intestinal microbial communities in both children and adults
• Competitively exclude pathogens
• Bacteriocin production
• Modulate enzymatic activities related to metabolisation of carcinogens and other toxic substances
• Produce volatile fatty acids – short-chain fatty acids and branched-chain fatty acids
• Increase intestinal cell adhesion and mucin production
• Modulate activity of gut-associated lymphoid tissue and the immune system.
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Spring fever: probiotics and allergy
The number of mast cells and the amount dermatitis (AD). Studies have mostly been
of mast cell-derived mediators such as on the administration of Lactobacillus and
histamine, the key mediator in allergy, are Bifidobacterium species in children with
increased at sites of allergic inflammation. atopy and many of these species have shown
The released mediators induce mucus and beneficial effects, including a reduction in
electrolyte secretion, smooth-muscle contrac- hyperreactivity and inflammation caused by
tion, nerve-cell activation and other symp- allergens and a decrease in cytokine release.
toms common in allergic reactions. Certain In the studies that have reported beneficial
probiotic bacteria might diminish mast cell results in children, these effects were found
allergy-related activation by downregulation to make allergy symptoms less aggressive,
of the expression of high-affinity IgE and thereby reducing morbidity.1
histamine receptor genes, and by inducing a
pro-inflammatory response.5 Lactobacillus reduces proinflammatory
responses by regulating nuclear factor kappa
Different studies examining the influence of B signalling and promoting the maturation of
Many studies probiotics on allergic diseases are equivocal dendritic cells that release IL-10, thus trigger-
have shown that and, as such, few practical recommenda- ing the differentiation and survival of regula-
probiotic intake tions guiding the use of probiotics in allergic tory T (Treg) cells. The regulation of Treg
diseases have been established. The different cells in intestinal immunity at a steady state is
at a minimum
effects of the same probiotic bacteria on dif- essential for sustaining tolerogenic response
of 1×109 cfu per ferent patients seemingly reinforce the idea by adaptive immunity.1,6
day in food and that the efficacy of probiotics is dependent
food supplements on the microbial species or strain, its derived Microarray analysis has been used to inves-
can support metabolites and by-products, and the gut tigate the effects of Lactobacillus rhamnosus
maturation and microbiota eubiosis of the patient. Many GG (LGG) on human mast cell gene expres-
modulation of studies have shown that probiotic intake at sion. LGG was observed to suppress genes
the immune a minimum of 1×109 colony forming units that encode allergy-related high-affinity IgE
(cfu) per day in food and food supplements receptor subunits α and γ (FCER1A and
system; the
can support maturation and modulation FCER1G, respectively) and the histamine H4
most promising of the immune system; the most promising receptor, the expression of genes involved
probiotics are probiotics are those belonging to the genera in mast cell immune system regulation, and
those belonging Lactobacillus and Bifidobacterium.1,2 several genes that encode proteins with a
to the genera pro-inflammatory impact such as IL-8 and
Lactobacillus and The most studied allergies on which pro- tumour necrosis factor (TNF)-α. LGG also
Bifidobacterium biotics have been shown to have a benefi- upregulates genes that encode proteins with
cial effect are rhinitis, asthma and atopic anti-inflammatory functions, such as IL-10.5
www.denovomedica.com
OCTOBER 2021 I 3
Spring fever: probiotics and allergy
ILC: innate lymphoid cells; PAMP: pathogen-associated molecular pattern molecules; Th: T helper cell; Treg: regulatory T cell; TSLP: thymic stromal lymphopoietin.
Figure 2. Immune tolerance (A) and breakdown of tolerance (B) to ingested antigens
https://www.emjreviews.com/allergy-immunology/symposium/human-milk-oligosaccharides-new-ways-to-shape-the-gut-
microbiome-in-cows-milk-protein-allergy/
Children with Typical IgE-mediated CMA symptoms extended hygiene hypothesis considers a lack
include urticaria, angioedema, vomiting, of microbial exposure during infancy to
CMA in the first
diarrhoea, and anaphylaxis. The majority of potentially be one of the factors contributing
year of life have affected children have one or more symptoms to CMA.6,7
an increased risk involving one or more organ systems, usually
of subsequently the gastrointestinal tract and/or skin. Many Allergen avoidance is not ideal in this set-
being affected infants develop symptoms in two or more ting because dairy products constitute a
by other atopic organ systems.6,7 high-quality source of calcium, potassium,
diseases; the protein, and vitamins B and D; avoidance of
extended hygiene Children with CMA in the first year of these foods can increase the risk of morbid-
life have an increased risk of subsequently ity, including bone fracture, osteoporosis and
hypothesis
being affected by other atopic diseases; the nutrient deficiencies.6,7
considers a lack
of microbial
exposure during The gut microbiota of children with CMA versus non-CMA
infancy to Compared to that of healthy children, the A different gut microbiota study of CMA
potentially be gut microbiota of children with CMA shows infants found dysbiosis characterised by
one of the factors enrichment in the relative abundance of fami- a prevalence of Haemophilus, Klebsiella,
contributing to lies Trichocomaceae and Ruminococcaceae as Prevotella, Actinobacillus and Streptococcus.
CMA well as genera Bacteroides and Alistipes, while Interestingly, Haemophilus, Prevotella,
a decrease in that of genus Bifidobacterium Actinobacillus and Streptococcus gradually
suggests that the gut microbiota of children decreased in the gut microbiota from CMA to
with CMA might be in an imbalanced state.5 cow’s milk-sensitised to healthy infants, lead-
A long-term investigation of gut micro- ing to the supposition that there is a correla-
biota of children with CMA showed that tion between these bacteria and allergic status.8
Firmicutes and Clostridia were enriched in
the infant gut microbiome of subjects whose There is some evidence suggesting the clini-
milk allergy resolved by the age of eight cal potential of probiotics for treating lactose
years, whereas Bacteroidetes and Enterobacter intolerance, as some probiotics promote lactose
were characteristic of subjects whose milk digestion by increasing the overall hydrolytic
allergy did not resolve by eight years of age. capacity in the small intestine and increasing
Specifically, there seems to be a link between the colonic fermentation, decreasing lactose
dysbiosis in the composition of the intestinal concentration in fermented products, and also
microbiota and the pathogenesis of CMA.2 increasing active lactase enzymes entering the
small intestine with the fermented products.2
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The investigators A study investigating the role of probiotics in baseline and after four weeks. TNSS changes
the treatment of AR when added as adjuvant from baseline at weeks 1, 3 and 4 were sig-
concluded that
agents to standard therapy in patients older nificant between the NVP-1703 and placebo
NVP-1703, than 15 years found no effect on the outcome groups (p=0.033, 0.031, and 0.029, respec-
containing B. of AR when using a commercial probiotic, tively). Serum IL-10 levels were significantly
longum and including strains of L. casei, L. acidophilus, different between the NVP-1703 and placebo
L. plantarum, L. rhamnosus, L. bulgaricus, B. breve, B. groups (p=0.033 and p=0.047, respectively).
can be a useful longum and S. thermophilus.13 IL-10/IL-4 and IL-10/IL-13 ratios differed
treatment option between the NVP-1703 and placebo groups at
for perennial AR However, the safety and efficacy of probiotic week 4 (p=0.046 and 0.018, respectively). The
NVP-1703, a mixture of B. longum and L. investigators concluded that NVP-1703, con-
plantarum, has been studied in adult par- taining B. longum and L. plantarum, can be a
ticipants with perennial AR. Total nasal useful treatment option for perennial AR.12
symptom scores (TNSS), rhinitis control
assessment test, blood eosinophil count, aller- A trial in adults with Japanese Cedar pollino-
gen-specific IgE, and immunological param- sis showed that daily consumption of 125ml
eters in serum and urine were compared at fermented citrus juice containing a heat-killed
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Spring fever: probiotics and allergy
APC: antigen-presenting cell; CRTH2: chemoattractant receptor-homologous molecule expressed on Th2 cells; dsRNA: double-stranded RNA; PGD2: prostaglandin D2; IFN: interferon; GRO: growth-
regulated oncogene; IL: interleukin; LPS: lipopolysaccharide; PAMP: pathogen-associated molecular pattern; ssRNA: single-stranded RNA; Th: T helper; TLR: Toll-like receptor.
Figure 4. Influence of the airway microbiota on responses to allergens, pollutants and pathogens
https://www.sciencedirect.com/science/article/pii/S0966842X15000591
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Spring fever: probiotics and allergy
Key learnings
• In allergic diseases there is a disturbance in the balance between Th1 and Th2 lymphocytes, in favour of
Th2 lymphocytes
• The most studied allergies on which probiotics have been shown to have a beneficial effect are rhinitis,
asthma and AD
• The most promising probiotics for the prevention and treatment of allergy are Lactobacillus and
Bifidobacterium species
• The gut microbiota of infants and children with CMA differs from the microbiota of healthy children;
there is some evidence for the clinical potential of probiotic supplementation against lactose intolerance
• Clinical and biomedical evidence exists for the beneficial effects of probiotics in respiratory allergy
disorders such as AR and asthma; trial evidence for the probiotic prevention of allergic airway disease
remains scarce
• The gut-skin axis is recognised as a new target for the prevention and treatment of AD; L. plantarum
supplementation has been shown to significantly improve symptoms.
References
Click on reference to access the scientific article
1. Lopez-Santamarina A, Gonzalez E, Lamas A, et al. Probiotics effectiveness of probiotic Lactobacillus rhamnosus and
as a possible strategy for the prevention and treatment of Lactobacillus casei strains in children with atopic dermatitis and
allergies. A narrative review. Foods 2021; 10(4): 701. cow’s milk protein allergy: a multicenter, randomized, double
2. Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, et al. Mechanisms blind, placebo controlled study. Nutrients 2021; 13: 1169.
of action of probiotics. Adv Nutr 2019; 10(suppl 1): S49-S66. 10. Thang CL, Baurhoo B, Boye JI, et al. Effects of Lactobacillus
3. Jakubczyk D, Gorska S. Impact of probiotic bacteria on rhamnosus GG supplementation on cow’s milk allergy in a
respiratory allergy disorders. Front Microbiol 2021; 12: 688137. mouse model. Allergy Asthma Clin Immunol 2011; 7(1): 20.
4. Spacova I, Ceuppens JL, Seys SF, et al. Probiotics against airway 11. Basturk A, Isik I, Atalay A, et al. Investigation of the efficacy of
allergy: host factors to consider. Dis Model Mech 2018; 11(7): Lactobacillus rhamnosus GG in infants with cow’s milk protein
dmm034314. allergy: a randomised double-blind placebo-controlled trial.
5. Oksaharju A, Kankainen M, Kekkonen RA, et al. Probiotic Probiotics Antimicrob Proteins 2020; 12(1): 138-143.
Lactobacillus rhamnosus downregulates FCER1 and HRH4 12. Kang MG, Han SW, Kang HR, et al. Probiotic NVP-1703
EARN FREE expression in human mast cells. World J Gastroenterol 2011; alleviates allergic rhinitis by inducing IL-10 expression: A four-
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10(11): 260. 19. Kim MH, Choi S, Choi HI, et al. Lactobacillus plantarum-derived
17. Fang Z, Li L, Zhang H, et al. Gut microbiota, probiotics, and extracellular vesicles protect atopic dermatitis induced by
their interactions in prevention and treatment of atopic Staphylococcus aureus-derived extracellular vesicles. Allergy
dermatitis: A review. Front Immunol 2021; 12: 720393. Asthma Immunol Res 2018; 10(5): 516-532.
18. Petersen EB, Skov L, Thyssen JP, et al. Role of the gut 20. Kim S, Lee SH, Kwon YM, et al. Oral administration of β-glucan
microbiota in atopic dermatitis: A systematic review. Acta Derm and Lactobacillus plantarum alleviates atopic dermatitis-like
Venereol 2019; 99(1): 5-11. symptoms. J Microbiol Biotechnol 2019; 29(11): 1693-1706.
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10 I OCTOBER 2021