Pulmonary pathologies

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Asthma

The intestinal and pulmonary microbiota may be involved in the onset of asthma. Research is in progress.

Asthma is a chronic inflammation of the bronchi that causes them to become hyperresponsive when exposed to certain substances or in certain situations. Around 235 million people are affected throughout the world1.

Multiple triggers

Asthma attacks are characterized by bronchial obstruction leading to breathing problems. They can be triggered by contact with an allergen, an irritant (pollution, smoke, paint, etc.), a respiratory virus, by certain medications, or even by physical activity2.

Role of the microbiota

Several studies suggest that there is a connection with intestinal microbiota dysbiosis3-6. For instance, low diversity in the latter in the first months of life3 or fecal colonization at three months with Bacteroides fragilis or Clostridium coccoides XIVa4 are risks factors for asthma . Furthermore, the use of antibiotics by the mother during pregnancy or by the child in the first year of life is associated with an increase in the risk of developing asthma for the child7. Dysbiosis brought on by antibiotics –occurring in the first weeks or even the first months of life, when the intestinal microbiota is being established8– may be related to an increased risk of developing asthma. The role of the pulmonary microbiota9 has also been identified. The discovery of a distinct and specific pulmonary flora suggests it plays a role in the development of asthma10-12. Conversely, exposure to microorganisms during early infancy may be beneficial in preventing asthma: it seems that there a reduced risk of developing asthma in children born vaginally13,14, or who are in contact with pets15 or farmanimals16.

Symptomatic treatment

The primary measures consist of eliminating triggers, if possible. Long-term and quick-relief treatments also reduce the frequency of attacks and control their severity. Furthermore, for allergic asthma, preclinical studies show that GOS and FOS prebiotics, as well as certain probiotics17,18, have a beneficial effect in modulating the immune response.

 

Sources:
1- OMS, avril 2017 http://www.who.int/mediacentre/factsheets/fs307/fr/
2- Recommandations GINA (2017) : Guide for asthma management and prevention. http://ginasthma.org/2017-pocket-guide-for-asthma-management-and-prevention/
3- 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 2013. doi: https://www.ncbi.nlm.nih.gov/pubmed/24330256 https://pdfs.semanticscholar.org/4421/476df50d20ba512ad954eb9867b6b10f3801.pdf
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 https://www.ncbi.nlm.nih.gov/pubmed/17827672
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 https://www.ncbi.nlm.nih.gov/pubmed/21477358
7- Murk W et al. Prenatal or early-life exposure to anti- biotics and risk of childhood asthma: a systematic review. Pediatrics 2011 ; 127 : 1125-38.
8- Azad MB, Kozyrskyj AL. Perinatal programming of asthma: the role of gut microbiota. Clin Dev Immunol 2012 ; 2012 : 932072.
9- Hilty M, Conor Burke et al. Disordered Microbial Communities in Asthmatic Airways. PLOS One. 2010 http://dx.doi.org/10.1371/journal.pone.0008578
10- Sullivan A et al. The Microbiome and the Pathophysiology of Asthma. Respir Res. 2016 Dec 5;17(1):163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5139145/
11- Hauptmann M et al. Linking microbiota and respiratory disease. FEBS Lett. 2016 Nov;590(21):3721-3738. https://www.ncbi.nlm.nih.gov/pubmed/27637588
12- Michon AL et al. Revue francophone des laboratoires.Février 2015 N°469 p37-49
13- Huang L, Chen Q, Zhao Y, Wang W, Fang F, Bao Y. Is elective cesarean section associated with a higher risk of asthma? A meta-analysis. J Asthma 2015;52:16-25.
14- Azad MB, Konya T, Maughan H, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 2013;185:385-94.
15- Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 2002;288:963-72.
16- Riedler J, Braun-Fahrlander C, Eder W, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 2001;358:1129-33.
17- 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. https://www.ncbi.nlm.nih.gov/pubmed/28122397
18- 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. https://www.ncbi.nlm.nih.gov/pubmed/28166610

Cystic fibrosis

Cystic fibrosis is a rare genetic disease that is characterized by serious respiratory and digestive disorders. The intestinal microbiota may be involved in the pathophysiology and progression of this disease.

Cystic fibrosis is a lethal recessive genetic disease, caused by mutations in the CFTR* gene. These mutations generate a deficiency or absence of functional CFTR proteins in the apical membrane of epithelial cells, leading to an increase in mucus viscosity and its accumulation in the respiratory and digestive tracts. In the digestive tract, the disease causes pancreatic insufficiency that affects digestion and nutrient absorption. In the lungs, it promotes infections by opportunistic bacteria (Staphylococcus aureus, Pseudomonas aeruginosa and Hemophilus influenzae), leading to the progressive loss of pulmonary function until the patient’s death.

Cystic fibrosis occurs in 1 in 2500 births in Europe and North America, while its prevalence is low in Africa and Asia1.

Dysbiosis and cystic fibrosis

The exacerbation of secretions also modifies the environment of the intestinal microbiota, and as such, its composition. A decline in microbiota diversity (changes in Firmicutes, Bacteroidetes, and Actinobacteria) has been observed in patients with cystic fibrosis compared to healthy volunteers. Multiple factors are at the root of this dysbiosis: the pathophysiology of the disease, the type of CFTR mutation, exposure to antibiotics, etc2,3.  This dysbiosis, which occurs very early in the individual’s life, contributes significantly to undernutrition, failure to thrive, and long-term morbidity4

 

Potential use of probiotics

Standard treatment targets airway clearance and digestive disorders: chest physiotherapy associated with bronchial decongestants, bronchodilators, and a hypercaloric diet including pancreatic extracts and vitamins.

In patients with cystic fibrosis, probiotics have been shown to reduce pulmonary exacerbation, intestinal inflammation, and the length of hospital stays5-8. Other studies, with larger cohorts and longer durations, are necessary to confirm the advantages of probiotics5‑8.

 

* Cystic Fibrosis Transmembrane conductance Regulator

 

Sources:
1- https://www.pasteur.fr/fr/centre-medical/fiches-maladies/mucoviscidose
2- Schippa S et al.  Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in fecal microbiota of cystic fibrosis patients. PLoS One. 2013;8:e61176.
3- Burke et al. 2017 The altered gut microbiota in adults with cystic fibrosis  Burke et al. BMC Microbiology (2017) 17:58
4- Juliette C Madan. Neonatal gastrointestinal and respiratory microbiome in cystic fibrosis : potential interactions and implications for systemic health. Clin ther 2016 ; 38 : 740-46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206974/
5- Bruzzese E et al. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther. 2004;20:813–9.
6- Bruzzese E et al.. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr. 2007;26:322–8
7- Weiss B et al.  Probiotic supplementation affects pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Pediatr Pulmonol. 2010;45:536–40.
8- del Campo R et al. Improvement of digestive health and reduction in proteobacterial populations in the gut microbiota of cystic fibrosis patients using a Lactobacillus reuteri probiotic preparation: a double blind prospective study. J Cyst Fibros. 2014;13:716–22.

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