What causes asthma? At a time when global rates of asthma have reached alarming rates, this important question remains unanswered. This debilitating disease affects approximately 339 million people globally, including 14% of all the children in the world. Even more troubling is its rapid rate of increase, with worldwide incidence increasing by 50% every decade (1).
Epidemiological studies have consistently associated the risk of asthma to different factors, including many that are related to our exposures to microbes early in life (2). Children that receive antibiotics during the first year of life, that are born by C-section, that are fed formula instead of breastmilk, or that suffer recurrent respiratory infections during infancy are at a higher risk of developing asthma. In contrast, children born and raised on farms or that grow up with a dog (but not a cat!) at home have a reduced risk of asthma (2).
With the advent of microbiome science, scientists have looked at the gut microbiome of babies that develop asthma later in life and compared them to those that stayed healthy. Intriguingly, several studies have now shown the babies that go on to develop asthma exhibit differences in their gut microbiome (3, 4)(5). In a previous study, Arrieta et al found that these microbiome alterations (also called dysbiosis) consisted of a decrease in four bacterial types they nicknamed FLVR (Faecalibacterium, Lachnospira, Veillonella, and Rothia) in 3-month-old babies (3). In this more recent study (6), they investigated a cohort of children in the province of Esmeraldas, in Ecuador — a very different place socioeconomically to Canada but with a very similar prevalence of asthma (~10%).
The epidemiological analysis in the Ecuadorian cohort study was revelatory and similar to other studies: babies born by C-section and that suffered more respiratory infection during their first year were more at risk of asthma. For the microbiome analysis, carried out in the laboratory of Dr. Brett Finlay at the University of British Columbia, the research team added a new group of microorganisms to their sequence-based surveys: fungi. Fungal organisms are as much part of the gut microbiome as bacteria yet they are rarely included in microbiome studies.
To their surprise, they found that the best predictor of asthma risk was not within Bacteria, but a genus of yeast known as Pichia. The species Pichia kudriavzevii was particularly elevated in babies at risk of asthma. They also found changes in bacterial populations, and, interestingly, these were different from the ones they have previously reported in Canadian babies (6). It is still unclear if these differences are due to the fact that the microbiome of Canadians is vastly different to the gut microbiome of the South American populations studied thus far and/or because of the different environmental exposures that differ between both locations.
It still remains to be known if and how these microbiome differences lead to disease. In the original study with Canadian babies, they demonstrated that FLVR bacteria made mice less prone to develop lung inflammation, a first in their field, yet there is much more to be shown. Can yeasts in the gut cause asthma? What about the lung microbiome? Can these new discoveries help prevent asthma? Lots of important questions remained unanswered. Stay tuned!
These findings are described in the article entitled Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting, recently published in the Journal of Allergy and Clinical Immunology. This work was conducted by Marie-Claire Arrieta from the University of British Columbia and University of Calgary, Andrea Arévalo from the Universidad Internacional del Ecuador, Leah Stiemsma from the University of British Columbia and University of California Los Angeles, Pedro Dimitriu, Rozlyn C.T. Boutin, Evan Morien, Stuart E. Turvey, Laura Wegener Parfrey, and Brett Finlay from the University of British Columbia, Martha E. Chico, Sofia Loor, and Maritza Vaca from the Fundación Ecuatoriana Para Investigación en Salud, Mingliang Jin and Jens Walter from the University of Alberta, Philip J. Cooper from the Universidad Internacional del Ecuador, St George’s University of London, and Fundación Ecuatoriana Para Investigación en Salud.
- Network GA. Global Asthma Report 2018. 2018 2018.
- Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014;5:427.
- Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015;7(307):307ra152.
- Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med. 2016;22(10):1187-91.
- Stokholm J, Blaser MJ, Thorsen J, Rasmussen MA, Waage J, Vinding RK, et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat Commun. 2018;9(1):141.
- Arrieta MC, Arevalo A, Stiemsma L, Dimitriu P, Chico ME, Loor S, et al. Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting. J Allergy Clin Immunol. 2018;142(2):424-34 e10.