Intestinal fungal dysbiosis associated with greater hospital use for asthma
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NASHVILLE, Tenn. — Intestinal fungal dysbiosis was associated with asthma severity, particularly hospital use in the previous year, with severity possibly exacerbated by crosstalk between the gut and the lung, according to study results.
In previous studies, Amjad N. Kanj, MD, a pulmonologist at Mayo Clinic in Rochester, Minnesota, and colleagues found that the expansion of Candida albicans and other dysbiosis-associated commensal fungi in the gut of mice enhanced asthma severity.
“Could it be that in select patients with uncontrolled asthma, intestinal fungal dysbiosis was a driver of their disease?” Kanj said during a presentation at CHEST Annual Meeting. “Our hypothesis was that intestinal fungal dysbiosis was associated with a lower Asthma Control Test (ACT) score and at least one asthma-related hospital use in the last year.”
Conducted between November 2020 and January 2022, the pilot study recruited 23 adults with asthma (median age, 59 years; interquartile range [IQR], 45-70 years; 74% women; 86% white; 74% never smokers) who completed a questionnaire and provided a stool sample. Also, they had a median ACT score of 17 (IQR, 15-19).
These patients had not used any antimicrobials or systemic glucocorticoids in the previous 30 days, although in the previous year, 57% had received antibiotics, 35% had ingested probiotics, 65% had received systemic glucocorticoids for asthma and 35% had at least one hospitalization or ED visit related to asthma.
“Median blood eosinophil count was 0.3, and our median FEV1 was 90% predicted,” Kanj said. “Most patients had a negative chest X-ray.”
The researchers extracted and measured the fungal and bacterial DNA in the stool samples and found a median fungal-to-bacterial DNA ratio of 1.9 x 10–4 (IQR, 0.5-13.7).
Upon analysis, the researchers did not find any association between intestinal fungal dysbiosis and FEV1, total serum IgE, blood eosinophil count, exhaled oral nitric oxide or ACT score at the time of the stool collection.
The researchers also did not find any statistically significant associations between fungal dysbiosis and any use of antibiotics, probiotics or systemic glucocorticoids in the previous year.
However, patients who had at least one hospitalization or ED visit had a significantly higher median fungal-to-bacterial DNA ratio than those patients who were not hospitalized or who did not visit the ED (19.6 x 10–4 vs. 0.9 x 10–4; P = .005).
“This association seemed to be independent of systemic antibiotic use in the last year, independent of systemic glucocorticoid use in the last year and independent of microorganisms use in the last year,” Kanj said.
Noting that many fungi that have an impact on asthma are part of the intestinal fungal microbiota, the researchers said that changes to the fungal microbiota of the gut can alter immune function in the lungs.
The researchers also said that further understanding of the role that intestinal dysbiosis plays in asthma could be helpful in identifying new mechanisms of disease severity as well as therapeutic targets for patients who have uncontrolled asthma.
“We hope that this study or future studies looking at this would help us understand the role of intestinal dysbiosis in asthma and help identify new mechanisms of disease severity in asthma patients,” Kanj said, “and also maybe answer the question of why some patients respond differently to events.”
Perspective
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Christopher O'Brien, MD, PhD, FCCP
This is a really interesting hypothesis-generating pilot study that found an association between expansion of well-known commensal fungi in the gut (C. albicans) with severe asthma exacerbations that seems to be independent of baseline lung function, asthma control, symptoms or prior therapies that typically impact gut microflora. I find this study particularly intriguing as researchers in therapeutics have increasingly recognized the gut microbiome as a key factor in a number of immunologic diseases.
Although the authors link these results to findings from a murine asthma model they had previously reported, it is not clear whether the association in the current study underlies a causal effect or is a sign of an immunologic disruption manifested in the gut that yields higher lability risk for patients with asthma.
Either outcome, causal or associated, in humans is interesting as it suggests possibilities for new mechanisms to target in patients with uncontrolled asthma as well as potential screening strategies to identify subpopulations/endotypes that are at particularly high risk despite currently available treatments.
Ultimately, confirmation and better understanding of the results of this pilot study will need to occur with larger datasets and longitudinal trials, but the results do parallel findings observed in other immune-mediated diseases (atopic dermatitis, for example) in which characteristic dysbiosis and alterations in the gut microbiome have been observed.
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Kanj AN, et al. Intestinal fungal dysbiosis is associated with higher asthma-related hospital use. Presented at: CHEST Annual Meeting; Oct. 16-19, 2022; Nashville, Tennessee.
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