Role of Antibiotics and Fungal Microbiota in Driving Pulmonary Allergic Responses

ABSTRACT Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics (the “hygiene hypothesis”). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators. We have developed a mouse model of antibiotic-induced microbiota disruption that includes stable increases in gastrointestinal (GI) enteric bacteria and GI Candida levels with no introduction of microbes into the lungs. Mice are treated for 5 days with cefoperazone in the drinking water, followed by a single oral gavage of C. albicans. This results in alterations of GI bacterial populations and increased yeast numbers in the GI microbiota for at least 2 to 3 weeks and can drive the development of a CD4 T-cell-mediated allergic airway response to subsequent mold spore (Aspergillus fumigatus) exposure in immunocompetent mice without previous systemic antigen priming. The allergic response in the lungs is characterized by increased levels of eosinophils, mast cells, interleukin-5 (IL-5), IL-13, gamma interferon, immunoglobulin E, and mucus-secreting cells. In the absence of antibiotics, mice exposed to Aspergillus spores do not develop an allergic response in the airways. This study provides the first experimental evidence to support a role for antibiotics and fungal microbiota in promoting the development of allergic airway disease. In addition, these studies also highlight the concept that events in distal mucosal sites such as the GI tract can play an important role in regulating immune responses in the lungs.

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Development of Allergic Airway Disease in Mice following Antibiotic Therapy and Fungal Microbiota Increase: Role of Host Genetics, Antigen, and Interleukin-13

Infection and Immunity ◽

10.1128/iai.73.1.30-38.2005 ◽

2005 ◽

Vol 73 (1) ◽

pp. 30-38 ◽

Cited By ~ 171

Author(s):

Mairi C. Noverr ◽

Nicole R. Falkowski ◽

Rod A. McDonald ◽

Andrew N. McKenzie ◽

Gary B. Huffnagle

Keyword(s):

Airway Disease ◽

Enteric Bacteria ◽

Epidemiological Studies ◽

Fecal Microbiota ◽

Allergic Airway Disease ◽

Allergic Response ◽

Gastrointestinal Microbiota ◽

Host Genetics ◽

Interleukin 13

ABSTRACT Lending support to the hygiene hypothesis, epidemiological studies have demonstrated that allergic disease correlates with widespread use of antibiotics and alterations in fecal microbiota (“microflora”). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators, from the microbiota. We have recently developed a mouse model of antibiotic-induced gastrointestinal microbiota disruption that is characterized by stable increases in levels of gastrointestinal enteric bacteria and Candida. Using this model, we have previously demonstrated that microbiota disruption can drive the development of a CD4 T-cell-mediated airway allergic response to mold spore challenge in immunocompetent C57BL/6 mice without previous systemic antigen priming. The studies presented here address important questions concerning the universality of the model. To investigate the role of host genetics, we tested BALB/c mice. As with C57BL/6 mice, microbiota disruption promoted the development of an allergic response in the lungs of BALB/c mice upon subsequent challenge with mold spores. In addition, this allergic response required interleukin-13 (IL-13) (the response was absent in IL-13−/− mice). To investigate the role of antigen, we subjected mice with disrupted microbiota to intranasal challenge with ovalbumin (OVA). In the absence of systemic priming, only mice with altered microbiota developed airway allergic responses to OVA. The studies presented here demonstrate that the effects of microbiota disruption are largely independent of host genetics and the nature of the antigen and that IL-13 is required for the airway allergic response that follows microbiota disruption.

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The Role of IgE in Upper and Lower Airway Disease: More Than Just Allergy!

Clinical Reviews in Allergy & Immunology ◽

10.1007/s12016-021-08901-1 ◽

2021 ◽

Author(s):

Philippe Gevaert ◽

Kit Wong ◽

Lauren A. Millette ◽

Tara F. Carr

Keyword(s):

Immunoglobulin E ◽

Allergic Sensitization ◽

Airway Disease ◽

Allergic Airway Disease ◽

Lower Airway ◽

Clinical Practices ◽

Optimal Care ◽

Airway Diseases ◽

Ige Mediated

AbstractImmunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non–IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.

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Bacterial-fungal interactions in the neonatal gut influence asthma outcomes later in life

eLife ◽

10.7554/elife.67740 ◽

2021 ◽

Vol 10 ◽

Author(s):

Rozlyn CT Boutin ◽

Charisse Petersen ◽

Sarah E Woodward ◽

Antonio Serapio-Palacios ◽

Tahereh Bozorgmehr ◽

...

Keyword(s):

Gut Microbiota ◽

Airway Disease ◽

Short Chain Fatty Acids ◽

Allergic Airway Disease ◽

Causal Association ◽

Pichia Kudriavzevii ◽

Asthma Risk ◽

Fungal Microbiota ◽

Fungal Interactions

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics.

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Long-Lasting Sensitization to Food During the First Two YearsPrecedes Allergic Airway Disease

PEDIATRICS ◽

10.1542/peds.104.2.s1.361a ◽

1999 ◽

Vol 104 (2) ◽

pp. 361-362

Author(s):

H. A. Sampson

Keyword(s):

Airway Disease ◽

Allergic Airway Disease

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Hubungan Antara Jenis Kelamin dan Riwayat Asma dengan Rinitis Alergi pada Pelajar SMP Muhammadiyah 3 Palembang

MEDICA ARTERIANA (Med-Art) ◽

10.26714/medart.2.1.2020.17-20 ◽

2020 ◽

Vol 2 (1) ◽

pp. 17

Author(s):

Meilina Wardhani ◽

Ressy Irma Juwita ◽

Mitayani Purwoko

Keyword(s):

Immunoglobulin E ◽

Cross Sectional ◽

Interleukin 5

Latar Belakang: Rinitis alergi adalah suatu penyakit pada hidung yang ditimbulkan oleh reaksi inflamasi mpada mukosa hidung dengan perantara immunoglobulin E. Prevalensi rinitis alergi di dunia telah meningkat termasuk di Indonesia yang kini telah mencapai 1,5-12.4% dan cenderung mengalami peningkatan setiap tahunnya. Penelitian ini bertujuan untuk mencari prevalensi rinitis alergi dan hubungan antara jenis kelamin dan riwayat asma dengan kejadian rinitis alergi pada siswa sekolah di Palembang. Metode: Penelitian ini adalah penelitian analitik observasional dengan desain cross sectional. Penelitian dilakukan di SMP Muhammadiyah 3 Palembang pada tahun 2018. Data primer diperoleh dengan cara meminta subjek penelitian untuk mengisi kuesioner ISAAC. Kriteria inklusi penelitian ini adalah siswa-siswi berusia 13-14 tahun. Besar sampel yang digunakan sebanyak 80 responden, diambil teknik total sampling.Hasil: Pada penelitian ini didapatkan prevalensi rinitis alergi sebesar 51,2% dan jenis kelamin (p=0,014) dan riwayat asma (p=0,019) sebagai faktor risiko terjadinya rinitis alergi. Perempuan lebih banyak menderita rinitis alergi dibanding laki-laki kemungkinan disebabkan perempuan lebih sering terpapar allergen berupa debu akibat sering melakukan pekerjaan rumah tangga seperti menyapu. Adanya paparan alergen terhadap mukosa hidung akan meningkatkan konsentrasi berbagai faktor yang terkait asma seperti eosinophil, interleukin-5 dan sel CD34 di darah perifer. Kesimpulan: Jenis kelamin dan riwayat asma merupakan faktor risiko terjadinya rinitis alergi pada anak.

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