The microbiome and development of allergic disease
Open accessAbstract
PURPOSE OF REVIEW: First, to review how the global rise in prevalence of asthma prompted studies of the relationships between microbial exposure in early infancy, the rate and pattern of development of immune function, and the development of allergic sensitization and of wheezing in childhood. And, second, to review how those studies laid the groundwork for a possible strategy for primary prevention of asthma through manipulation of the microbiome of the gastrointestinal and/or respiratory tracts. RECENT FINDINGS: Atopy and asthma are complex diseases thought to result from a 'gene-by-environment' interaction; the rapidity of their rise in prevalence points to a change in environment as most likely causal. Epidemiologic studies noting associations between events in infancy and later development of atopic diseases have suggested that their rise in prevalence is related to a deficiency in microbial exposure in early life. The findings from birth cohort studies of humans and from interventional studies of mice converge in suggesting that a deficiency in microbial colonization of the respiratory or gastrointestinal tract by certain commensal microbes results in skewed development of systemic and/or local immune function that increases susceptibility to allergic sensitization and to viral lower respiratory infection. Recent studies are now honing in on identifying the microbes, or collection of microbes, whose collective functions are necessary for induction of immune tolerance, and thus of reduced susceptibility. SUMMARY: Atopy and asthma appear to have their roots in an insufficiency of early-life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts with the commensal microbes necessary for induction of balanced, toleragenic immune function. Identification of the commensal bacteria necessary, now ever closer at hand, will lay the groundwork for the development of strategies for primary prevention of atopic disease, especially of childhood asthma.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Observational studies have linked exposure to indoor allergens such as dust mites, cockroaches, and rodents to increased asthma risk, while early pet exposure may have a protective effect.
“While observational studies have linked exposure to indoor allergens such as dust mites, cockroaches, and rodents to increased asthma risk, there is evidence, particularly with regard to early pet exposure suggesting a potential protective effect (64).”
From Indoor Allergen Interventions in Homes and Schools for Managing Asthma (2025) · cites this paper as [64]
The Early Life Environment section says early exposure to household pets, especially dogs, is associated with lower childhood asthma rates. It does not substantiate the claimed observational link between dust mites, cockroaches, or rodents and increased asthma risk; instead, it describes lower atopy and recurrent wheeze among children with high exposure to both microbes and allergens, and suggests rodents or cockroaches may help create protective environments. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredExposure to dogs in early infancy has been associated with lower asthma risk.
“Exposure to dogs in early infancy has been associated with lower asthma risk (64).”
From Indoor Allergen Interventions in Homes and Schools for Managing Asthma (2025) · cites this paper as [64]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hay fever, hygiene, and household size.
Strachan, D. P. (1989) · BMJ · doi:10.1136/bmj.299.6710.1259 · Cited by 5,054 · see citing works
The gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029 · see citing works
Dominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774 · see citing works
The global burden of asthma: executive summary of the GINA Dissemination Committee Report
Masoli, M., Fabian, D., Holt, S., Beasley, R. W., & Program, G. I. F. A. (. (2004) · Allergy · doi:10.1111/j.1398-9995.2004.00526.x · Cited by 3,521 · see citing works
Atopic Dermatitis: Global Epidemiology and Risk Factors
Nutten, S. (2015) · Annals of Nutrition and Metabolism · doi:10.1159/000370220 · Cited by 3,077 · see citing works
Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis
Trompette, A., Gollwitzer, E. S., Yadava, K., Sichelstiel, A. K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L. P., Harris, N. L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3444 · Cited by 2,862 · see citing works
The Placenta Harbors a Unique Microbiome
Aagaard, K., Ma, J., Antony, K. M., Ganu, R., Petrosino, J., & Versalovic, J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008599 · Cited by 2,494 · see citing works
Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children
Braun‐Fahrländer, C., Riedler, J., Herz, U., Eder, W., Waser, M., Grize, L., Maisch, S., Carr, D., Gerlach, F., Bufe, A., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020057 · Cited by 1,810 · see citing works
Early infancy microbial and metabolic alterations affect risk of childhood asthma
Arrieta, M., Stiemsma, L. T., Dimitriu, P. A., Thorson, L., Russell, S., Yurist‐Doutsch, S., Kuzeljevic, B., Gold, M. J., Britton, H. M., Lefebvre, D. L., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aab2271 · Cited by 1,784 · see citing works
Eder, W., Ege, M. J., & von Mutius, E. (2006) · New England Journal of Medicine · doi:10.1056/nejmra054308 · Cited by 1,621 · see citing works
Interactions between commensal intestinal bacteria and the immune system
Macpherson, A. J., & Harris, N. L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1373 · Cited by 1,607 · see citing works
Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey
Riedler, J., Braun-Fahrländer, C., Eder, W., Schreuer, M., Waser, M., Maisch, S., Carr, D., Schierl, R., Nowak, D., & von Mutius, E. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06252-3 · Cited by 1,520 · see citing works
A longitudinal, population-based, cohort study of childhood asthma followed to adulthood
Sears, M. R., Greene, J. M., Willan, A. R., Wiecek, E. M., Taylor, D. R., Flannery, E. M., Cowan, J. O., Herbison, G. P., Silva, P. A., & Poulton, R. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022363 · Cited by 1,460 · cited 1× · see citing works
“While effective therapies for controlling asthma are available, none is curative, and the disease often persists from early childhood through adult life [6].”
Pearce, N. E., Ait-Khaled, N., Beasley, R. W., Mallol, J., V, Keil, U., Mitchell, E. A., Robertson, C., & and the ISAAC Phase Three Study Group (2007) · Thorax · doi:10.1136/thx.2006.070169 · Cited by 1,257 · see citing works
Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing
Kalliomäki, M., Kirjavainen, P., Eerola, E., Kero, P., Salminen, S., & Isolauri, E. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.111237 · Cited by 1,255 · see citing works
Allergy development and the intestinal microflora during the first year of life
Björkstén, B., Sepp, E., Julge, K., Voor, T., & Mikelsaar, M. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.118130 · Cited by 1,203 · see citing works
Family size, infection and atopy: the first decade of the 'hygiene hypothesis'
Strachan, D. (2000) · Thorax · doi:10.1136/thorax.55.suppl_1.s2 · Cited by 1,183 · see citing works
The intestinal microflora in allergic Estonian and Swedish 2‐year‐old children
Björkstén, Naaber, P., Sepp, & Mikelsaar (1999) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1999.00560.x · Cited by 927 · see citing works
Prevalence of Asthma and Atopy in Two Areas of West and East Germany
von Mutius, E., Martinez, F. D., Fritzsch, C., Nicolai, T., Roell, G., & Hh, T. (1994) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.149.2.8306030 · Cited by 897 · see citing works
Extrathymically generated regulatory T cells control mucosal TH2 inflammation
Josefowicz, S. Z., Niec, R. E., Kim, H. Y., Treuting, P. M., Chinen, T., Zheng, Y., Umetsu, D. T., & Rudensky, A. Y. (2012) · Nature · doi:10.1038/nature10772 · Cited by 823 · see citing works
Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota
Smith, K., McCoy, K. D., & Macpherson, A. J. (2006) · Seminars in Immunology · doi:10.1016/j.smim.2006.10.002 · Cited by 789 · see citing works
Kusel, M. M. H., de Klerk, N. H., Kebadze, T., Vohma, V., Holt, P. G., Johnston, S. L., & Sly, P. D. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.12.669 · Cited by 740 · see citing works
Ownby, D. R. (2002) · JAMA · doi:10.1001/jama.288.8.963 · Cited by 736 · see citing works
The genetics of asthma and allergic disease: a 21st century perspective
Ober, C., & Yao, T. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01029.x · Cited by 698 · see citing works
Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells
Schuijs, M. J., Willart, M. A., Vergote, K., Gras, D., Deswarte, K., Ege, M. J., Madeira, F. B., Beyaert, R., van Loo, G., Bracher, F., et al. (2015) · Science · doi:10.1126/science.aac6623 · Cited by 576 · see citing works
Risk factors for asthma: is prevention possible?
Beasley, R. W., Semprini, A. C., & Mitchell, E. A. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00156-7 · Cited by 512 · see citing works
The allergy epidemics: 1870-2010
Platts‐Mills, T. A. E. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.03.048 · Cited by 440 · see citing works
Fujimura, K. E., Demoor, T., Rauch, M., Faruqi, A. A., Jang, S., Johnson, C. C., Boushey, H. A., Zoratti, E. M., Ownby, D. R., Lukacs, N. W., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310750111 · Cited by 422 · see citing works
Self-citationArshad, S. H., Tariq, S. M., Matthews, S., & Hakim, E. A. (2001) · PEDIATRICS · doi:10.1542/peds.108.2.e33 · Cited by 420 · see citing works
Intestinal microflora of Estonian and Swedish infants
Sepp, E., Julge, K., Vasar, M., Naaber, P., Björkstén, B., & Mikelsaar, M. (1997) · Acta Paediatrica · doi:10.1111/j.1651-2227.1997.tb15178.x · Cited by 416 · see citing works
Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome
Fujimura, K. E., & Lynch, S. V. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.007 · Cited by 414 · see citing works
Self-citationLynch, S. V., Wood, R. A., Boushey, H. A., Bacharier, L. B., Bloomberg, G. R., Kattan, M., O’Connor, G. T., Sandel, M. T., Calatroni, A., Matsui, E. C., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.04.018 · Cited by 392 · see citing works
Self-citationTariq, S. M., Matthews, S., Hakim, E. A., Stevens, M., Arshad, S. H., & Hide, D. W. (1998) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(98)70164-2 · Cited by 370 · see citing works
Ochoa-Repáraz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001443 · Cited by 367 · see citing works
Caesarean section delivery and the risk of allergic disorders in childhood
Renz‐Polster, H., David, M., Buist, A. S., Vollmer, W. M., O’Connor, E., Frazier, E. A., & Wall, M. A. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02356.x · Cited by 339 · see citing works
Rook, G. A. W. (2010) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2010.04133.x · Cited by 332 · see citing works
An Estimate of the Prevalence of Asthma and Wheezing Among Inner-City Children
Crain, E. F., Weiss, K. B., Bijur, P. E., Hersh, M., Westbrook, L. E., & Stein, R. E. K. (1994) · PEDIATRICS · doi:10.1542/peds.94.3.356 · Cited by 331 · see citing works
Fungi as a Cause of Allergic Disease
Gravesen, S. (1979) · Allergy · doi:10.1111/j.1398-9995.1979.tb01562.x · Cited by 330 · see citing works
Conrad, M. L., Ferstl, R., Teich, R., Brand, S., Blümer, N., Yildirim, A. Ö., Patrascan, C. C., Hanuszkiewicz, A., Akira, S., Wagner, H., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090845 · Cited by 317 · see citing works
Prevalence, Impact, and Trends in Childhood Disability Due to Asthma
Newacheck, P. W., & Halfon, N. (2000) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.154.3.287 · Cited by 311 · see citing works
Waser, M., Michels, K. B., Bieli, C., Flöistrup, H., Pershagen, G., von Mutius, E., Ege, M. J., Riedler, J., Schram-Bijkerk, D., Brunekreef, B., et al. (2006) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2006.02640.x · Cited by 280 · see citing works
Kurup, V. P., Shen, H.-D., & Banerjee, B. (2000) · Microbes and Infection · doi:10.1016/s1286-4579(00)01264-8 · Cited by 255 · see citing works
The role and abatement of fungal allergens in allergic diseases
Bush, R. K., & Portnoy, J. M. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.113669 · Cited by 251 · see citing works
Man's best friend? The effect of pet ownership on house dust microbial communities
Fujimura, K. E., Johnson, C. C., Ownby, D. R., Cox, M. J., Brodie, E., Havstad, S. L., Zoratti, E. M., Woodcroft, K. J., Bobbitt, K. R., Wegienka, G., et al. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.05.042 · Cited by 244 · see citing works
Self-citationWeiss, K. B., Gergen, P. J., & Crain, E. F. (1992) · CHEST Journal · doi:10.1378/chest.101.6_supplement.362s · Cited by 235 · see citing works
The Childhood Origins of Asthma (COAST) study
Lemanske, R. F. (2002) · Pediatric Allergy and Immunology · doi:10.1034/j.1399-3038.13.s.15.8.x · Cited by 220 · see citing works
Farm exposurein uteromay protect against asthma, hay fever and eczema
Douwes, J. E., Cheng, S.-L., Travier, N., Cohet, C., Niesink, A., McKenzie, J. S., Cunningham, C., Gros, G. S. L., von Mutius, E., & Pearce, N. E. (2008) · European Respiratory Journal · doi:10.1183/09031936.00033707 · Cited by 207 · see citing works
Mode of delivery and risk of allergic rhinitis and asthma
Bager, P., Melbye, M., Rostgaard, K., Benn, C. S., & Westergaard, T. (2003) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2003.34 · Cited by 163 · see citing works
Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma
Fall, T., Lundholm, C., Örtqvist, A. K., Fall, K., Fang, F., Hedhammar, Å., Kämpe, O., Ingelsson, E., & Almqvist, C. (2015) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2015.3219 · Cited by 157 · see citing works
Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis
Penders, J., Kummeling, I., & Thijs, C. T. (2011) · European Respiratory Journal · doi:10.1183/09031936.00105010 · Cited by 149 · see citing works
Inner-city asthma. The epidemiology of an emerging US public health concern
Weiss, K., Gergen, P. J., & Crain, E. F. (1992) · CHEST Journal · doi:10.1378/chest.101.6.362s · Cited by 143 · see citing works
Genuneit, J. (2012) · Pediatric Allergy and Immunology · doi:10.1111/j.1399-3038.2012.01312.x · Cited by 116 · see citing works
Microbiota in autoimmunity and tolerance
Atarashi, K., & Honda, K. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.11.002 · Cited by 115 · see citing works
Breastfeeding Protects against Current Asthma up to 6 Years of Age
Silvers, K. M., Frampton, C. M., Wickens, K. L., Pattemore, P., Ingham, T. R., Fishwick, D., Crane, J., Town, G. I., & Epton, M. (2012) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2011.11.055 · Cited by 108 · see citing works
Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop
Bousquet, J., Gern, J. E., Martínez, F. D., Antó, J. M., Johnson, C. C., Holt, P. G., Lemanske, R. F., Souëf, P. N. L., Tepper, R. S., von Mutius, E., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.01.018 · Cited by 97 · see citing works
Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases
Jackson, D. J., Hartert, T. V., Martínez, F. D., Weiss, S. T., & Fahy, J. V. (2014) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201312-448ld · Cited by 65 · see citing works
Holt, P. G. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.05.011 · Cited by 43 · see citing works
Promising candidates for allergy prevention
Gern, J. E. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.05.017 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Development of the gut microbiota in infancy and its impact on health in later life
Tanaka, M., & Nakayama, J. (2017) · Allergology International · doi:10.1016/j.alit.2017.07.010 · Cited by 639 · see citing works
The promise of the gut microbiome as part of individualized treatment strategies
Schupack, D. A., Mars, R. A. T., Voelker, D. H., Abeykoon, J. P., & Kashyap, P. C. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00499-1 · Cited by 217 · see citing works
Duar, R. M., Kyle, D., & Casaburi, G. (2020) · High-Throughput · doi:10.3390/ht9020007 · Cited by 70 · see citing works
Indoor Allergen Interventions in Homes and Schools for Managing Asthma
Beheshti, R., Phipatanakul, W., DiMango, E., & Grant, T. L. (2025) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2025.04.027 · Cited by 6 · see citing works
- Authors
- Lynch, S. V., & Boushey, H. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Boushey, Homer A.
- Venue
- Current Opinion in Allergy & Clinical Immunology
- Published
- 2016-04
- Volume
- 16
- Issue
- 2
- Pages
- 165-171
- ISSN
- 1473-6322 (ISSN-L)
- 1528-4050
- PMC
- PMC5378446
- OpenAlex
- W2398650586
- Cited by
- 92
- References
- 58
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 13 · 2018: 12 · 2017: 12 · 2016: 4
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Gilead Sciences
- National Heart, Lung, and Blood Institute (HL09896, U10HL0988107, U10HL098107, F32HL009896)
- National Institute of Allergy and Infectious Diseases (AI097172, UM1AI114271, R01AI097172, P01AI089473)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK104664, R21DK104664)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- microbiome, allergic diseases, asthma, atopy, microbial exposure, early life colonization, commensal bacteria, immune tolerance, immune system development, wheezing, allergen sensitization, primary prevention, gene-environment interaction, gut microbiota, respiratory microbiota
- MeSH terms
- Animals, Asthma, Biological Therapy, Environmental Exposure, Humans, Hypersensitivity, Immune System, Immune Tolerance, Infant, Intestines, Respiratory System, Mice, Gene-Environment Interaction, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
