Allergics

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Food allergies

Although allergies are multifactorial diseases, they most often result from an abnormal immune response to allergens. This disorder may be due to a microbiota imbalance.

Food allergies (FA) are increasingly common in developed countries. In Europe, the prevalence of FA is 4.7% in children and 3.2% in adults. In France, around 5% of the population is allergic1. FA are related to an hypersensitivity to dietary proteins, most often IgE-dependent. In children, five specific allergens are responsible for 82% of FA: chicken eggs, peanut, cow’s milk, mustard, and fish, to which are added, in adults, shellfish, wheat, and nuts2

An identified immune mechanism

To explain these allergies, researchers suppose that the proper maturation of the immune system requires repeated exposure to new bacterial antigens, and that the impoverishment of the microbial ecosystem promotes the development of inappropriate immune responses to antigens that are normally inoffensive3.

An obvious connection to intestinal microbiota

Epidemiological observations have very quickly connected allergic phenomena with microbiota alteration: all allergic patients have a different microbiota than healthy individuals4,5. It has been shown that dysbiosis is present in allergic individuals and bacteria belonging to the Clostridia, Proteobacteria, Bacteroidetes and Actinobacteria6-9 classes are particularly involved in cases of FA.

Therapeutic microbiota?

Results suggest than modulating the microbiota could help prevent allergies, through the use of probiotics and prebiotics. A large number of studies exist on the positive effects of probiotics in animal models (mice, rats, pigs) of sensitization to food allergies, atopic dermatitis, and asthma10.
 

 

Sources:
1 - Moneret-Vautrin DA. Épidémiologie de l’allergie alimentaire Revue française d’allergologie et d’immunologie clinique 2008 ; 48 : 171–178 .
2 – Rona RJ et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 2007 ; 120:638–46. 
3 - Omenetti   S. et al. The   Treg/Th17 axis : a dynamic   balance regulated by the gut microbiome. Front Immunol 2015 ; 6 : 639.
4 - Panzer  AR et al. Influence and  effect of the human  microbiome in allergy and asthma. Curr Opin Rheumatol   2015 ; 27(4) : 373–80.
5 - Drell T et al. Differences in Gut Microbiota Between Atopic and Healthy Children. Curr Microbiol 2015 ; 71 : 177-83.
6 - Thompson-Chagoyan OC et al. Faecal microbiota and short-chain fatty acid levels in faeces from infants with cow’s milk protein allergy. Int Arch Allergy Immunol 2011 ; 156 : 325-32.
7 - Candela M et al. Unbalance of intestinal microbiota in atopic children. BMC Microbiol 2012 ; 12 : 95.
8 -  Ling Z, Li Z, Liu X, et al. Altered fecal microbiota composition associated with food allergy in infants. Appl Environ Microbiol 2014 ; 80 : 2546-54.
9 - Sepp E, Julge K, Mikelsaar M, Björkstén B. Intestinal microbiota and immunoglobulin E responses in 5-year-old Estonian children. Clin Exp Allergy 2005 ; 35 : 1141-6.
10 - de Azevedo MS, Innocentin S, Dorella FA, et al. Immunotherapy of allergic diseases using probiotics or recombinant probiotics. J Appl Microbiol 2013 ; 115 : 319-33.

Allergic asthma

Imbalances in intestinal flora in infants favors the development of allergic asthma. Studies have been carried out on the prevention of allergic asthma with probiotics or prebiotics. 

Allergic origin

The prevalence of asthma is estimated at 14% in children and around 6% in adults1. This inflammatory disease of the bronchi has an allergic origin in most cases. The allergen can be of various origins: pollen, tobacco, food, pollution; a personal history of atopy or allergic rhinitis in childhood also increases the risk of asthma2. Furthermore, the occurrence of certain events can modify intestinal flora in very early life (cesarean birth, use of antibiotics), and are likely to increase the risk of allergies and asthma as a result3

Intestinal microbiota dysbiosis

Several studies have established a connection with an intestinal microbiota dysbiosis4-6, but also with a pulmonary microbiota dysbiosis7,8, which suggests that these bacterial ecosystems play a role in allergic asthma, though without establishing a clear effect on the microbiota of these patients. An increase in the level of colonization by Bacteroidaceae and/or colonization by the species Bacteroides fragilis at the age of 3 weeks have been associated with an increased risk of developing asthma later in life9. Generally speaking, low diversity in the intestinal microbiota in the first weeks of life is associated with a higher risk of sensitivity and respiratory allergies10,11

Prebiotics and probiotics as prevention

Currently, treatment relies on the removal of the allergen associated to long-term control medication and fast-acting medication for excerbations.
The relationship between intestinal microbiota and allergy suggests that changes to the microbiota could prevent or reduce allergies. According to the literature, GOS and FOS prebiotics have an effect in some allergic asthma models12. Furthermore, several studies have shown positive effects of probiotics on asthma in animal models13-15
 

Sources:
1. Global burden of disease due to asthma. The global Asthma Report 2014. http://www.globalasthmareport.org/burden/burden.php 
2. Rhinitis and onset of asthma: a longitudinal population-based study. Shaaban R, Zureik M, Soussan D et al. Lancet. 2008 Sep 20;372(9643):1049-57.
3. Pearl D. Houghteling et al. From Birth to “Immunohealth,” Allergies and Enterocolitis. J Clin Gastroenterol 2015;49:S7–S12 
4. Vael C, Nelen V, Verhulst S, Goossens H, Desager K. Early intestinal Bacteroides fragilis colonisation and development of asthma. BMC Pulm Med 2008: 8: 19 https://www.ncbi.nlm.nih.gov/pubmed/18822123
5. Songjinda P, Nakayama J, Tateyama A, et al. Differences in developing intestinal microbiota between allergic and nonallergic infants: a pilot study in Japan. Biosci Biotechnol Biochem 2007 ; 71 : 2338-42
6. Vael C, Vanheirstraeten L, Desager KN, Goossens H. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma. BMC Microbiol 2011 ; 11 : 68
7. Hilty M, Conor Burke et al. Disordered Microbial Communities in Asthmatic Airways. PLOS One. 2010 http://dx.doi.org/10.1371/journal.pone.0008578
8. Millares L, Bermudo G, Pérez-Brocal V, et al. The respiratory microbiome in bronchial mucosa and secretions from severe IgE-mediated asthma patients. BMC Microbiology. 2017;17:20.doi:10.1186/s12866-017-0933-6.
9. Vael C et al. Early intestinal Bacteroides fragilis colonisation and development of asthma. BMC Pulm Med. 2008 Sep 26;8:19
10. Bisgaard H, Li N, Bonnelykke K, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 2011 ; 128 : 646-52. 
11. Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy 2014 ; 44 : 842-50. 
12. Vos AP, van Esch BC, Stahl B, et al. Dietary supplemen- tation with specific oligosaccharide mixtures decreases para- meters of allergic asthma in mice. Int Immunopharmacol 2007 ; 7 : 1582-7. 
13. de Azevedo MS, Innocentin S, Dorella FA, et al. Immuno- therapy of allergic diseases using probiotics or recombinant probiotics. J Appl Microbiol 2013 ; 115 : 319-33.
14. Fonseca VM, Milani TM, Prado R, Bonato VL, Ramos SG, Martins FS, Vianna EO, Borges MC . Oral administration of Saccharomyces cerevisiae UFMG A-905 prevents allergic asthma in mice. Respirology. 2017 Feb 6. doi: 10.1111/resp.12990 . [Epub ahead of print] PMID: 28166610 
15. Juan Z, Zhao-Ling S, Ming-Hua Z, Chun W, Hai-Xia W, Meng-Yun L, Jian-Qiong H, Yue-Jie Z, Xin S. Oral administration of Clostridium butyricum CGMCC0313-1 reduces ovalbumin-induced allergic airway inflammation in mice. Respirology. 2017 Jan 25. doi: 10.1111/resp.12985 . [Epub ahead of print] PMID: 28122397

Allergic rhinitis

Allergic rhinitis, the most common manifestation of respiratory allergy, frequently progresses to allergic asthma. It is associated with dysbiosis in the gastrointestinal and ENT microbiota.

A common hereditary disease

Allergic rhinitis is a very common disease, and the number of cases continues to climb worldwide. Around 500 million people are affected1. It starts with exposure to an allergen and can be intermittent or persistent, depending on the nature of that allergen (pollen, dust mites, pet dander, etc.). Symptoms include itching, anosmia, rhinorrhea, nasal obstruction, and sneezing. The hereditary component of respiratory allergy is well documented; if both parents are allergic, in 7 out of 10 cases the individual will also be allergic2

Allergic rhinitis and allergic asthma

Around 20% of people with allergic rhinitis have asthma and 80% of asthmatics have rhinitis3. Clinical and epidemiological studies have established a connection between microbiota, allergic rhinitis, and asthma.

Microbiota dysbiosis 

Among the characteristics these diseases have in common, there is low diversity in the intestinal microbiota during the first weeks of life4,5. Lactobacilli in particular are less present in allergic individuals, and they are known as bacteria that limit the proliferation of pathogens in the bowel and promote immunoregulation by stimulating regulatory T cells responses. Conversely, a greater diversity of bacteria is found in the ENT microbiota6, which can contribute to chronic inflammation and symptoms observed in these patients.

Probiotics under investigation

Currently, treatment for allergic rhinitis is based on removal of the allergen and preventive or curative antihistamine treatment. Topical corticosteroids can help with exacerbation episodes. Research is also being directed at modulating the microbiota to reduce allergic risk, using probiotics like Lactobacillus plantarum and Lactobacillus paracasei7,8.

 

Sources:
1. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision. The Journal of Allergy and Clinical  Immunology, septembre 2010, vol. 126(3): 466-476 http://www.jacionline.org/article/S0091-6749(10)01057-2/pdf
2. Dávila I, Mullol J, Ferrer M, Bartra J, del Cuvillo A, Montoro J, Jáuregui I, Sastre J, Valero A. Genetic aspects of allergic rhinitis. J Investig Allergol. Clin Immunol. 2009;19 Suppl 1:25-31. Review. PubMed PMID: 19476051.
3. Mullol J. et al. Allergic Rhinitis and its Impact on Asthma Update (ARIA 2008) : the perspective from Spain. J Investig Allergol Clin Immunol 2008 ;18 :327-334 https://www.ncbi.nlm.nih.gov/pubmed/18973095
4. Bisgaard H et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 2011 ; 128 : 646-52. https://www.ncbi.nlm.nih.gov/pubmed/21782228
5. L.C.F.L. Melli et al. Intestinal microbiota and allergic diseases: A systematic review. Allergol Immunopathol (Madr). 2016;44(2):177-188 https://www.ncbi.nlm.nih.gov/pubmed/25985709
6. Choi CH, Watanabe S et al. Seasonal allergic rhinitis affects sinonasal microbiota. Am Journal of Allergy, 2014 Jul;28(4):281-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101129
7. Peng GC et al. The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite. Pediatr Allergy Immunol. 2005;16:433–8 https://www.ncbi.nlm.nih.gov/pubmed/16101937 
8. Yang G. et al. Treatment of Allergic Rhinitis with Probiotics: An Alternative Approach. North American Journal of Medical Sciences, 5(8), 465–468. http://doi.org/10.4103/1947-2714.117299

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