Patients with asthma and allergic rhinitis may have different fungi in their noses
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Key takeaways:
- Patients with allergic rhinitis and comorbid asthma showed higher nasal mycobiome diversity.
- Healthy participants had significantly different fungal composition.
Patients with sniffles because of allergic conditions have different living fungi within their noses compared with healthy people, according to a study conducted in Portugal and published in Frontiers in Microbiology.
“Allergic rhinitis (AR) and asthma are, globally, two of the most common chronic respiratory diseases seen in an allergy clinic, particularly in children,” Luis Delgado, MD, PhD, FAAAAI, professor of immunology in the department of pathology at Faculdade de Medicina, Universidade do Porto(FMUP), in Portugal, told Healio.
“Although in the last 2 decades, multiple studies have investigated the role of microbial interactions, especially environmental and gut bacterial communities, in allergic disease development, little is known about the upper airway fungal communities (mycobiota) and their potential association with airway allergic inflammatory diseases,” Delgado, who also heads the Basic & Clinical Immunology Service and the Immunology Lab at FMUP, said.
He further explained that allergic rhinitis and asthma frequently occur together and nearly half of the Portuguese patients with asthma also showed AR.
“It has been suggested that they represent a combined airway inflammatory disease – the concept of ‘one-airway-one-disease,’ also the basis of the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines, currently widely used in the diagnostic and combined management of these respiratory diseases,” Delgado said.
He also noted that several studies suggest that rhinitis alone and rhinitis with comorbid asthma may represent two distinct diseases with different allergens. He cited a study by Bousquet and colleagues that hypothesizes that the onset of these two distinct diseases is possibly modulated by the microbiome.
Delgado and his research team studied this hypothesis using nasal DNA samples to characterize nasal fungal communities, or the mycobiome, in patients with AR and/or asthma.
“These are mainly allergic patients, sensitized (ie, with IgE production) to house dust mites, pollens, cat or dog dander,” Delgado said.
Methods
Study participants were taken from the ASMAPORT project, a cross-sectional study that examined host-microbe relationships during asthma and AR in adults and children in Portugal. Participants were recruited from an outpatient clinic in northern Portugal from July 2018 to January 2020.
An allergy specialist confirmed a diagnosis of AR by a positive skin prick test or IgE test. An asthma diagnosis was confirmed by a physician based on symptoms in the past 12 months or a positive bronchodilator test with salbutamol.
In total, the study included 339 participants (median age 12.5 ± 5 years; 53.7% female). They were divided into an AR group (n = 47), an AR with asthma group (n = 155), an asthma group (n = 12) and a healthy control group (n = 125).
Nasal samples were collected from all 339 participants by swabbing the left and right nostrils. To characterize each participant’s nasal mycobiomes, the research team sequenced internal transcriber spacers ITS1 and ITS2 with high throughput sequencing.
Results
After quality control, a final ITS1 and ITS2 data set of 306 samples were sequenced with 42 samples from 36 participants in the AR group, 142 samples from 130 participants in the AR with asthma group, 12 samples from 12 participants in the asthma group and 110 samples from 108 participants in the control group.
The nasal mycobiome dataset had 6,145,342 clean reads that ranged from 1,014 to 223,989 sequences per sample with a mean of 20,082.8 and a total of 5,635 internal transcriber spacer amplicon sequence variants (ASV).
The AR samples had 570 unique ASVs (10.1%), the AR with asthma group had 2,202 unique reads (39.1%), the asthma group had 138 unique samples (2.4%) and the control group had 1,615 (28.7%). Among all four groups, 122 ASVs were shared. Within the respiratory illness groups, 78 ASVs were shared.
All the sequenced samples were divided into two dominant Phyla. The first was Ascomycota (54.0%) and the second, Basidiomycota (44.9%). These Phyla contained 14 dominant genera, the most abundant being Cladosporium (23.0%), Wallemia (8.9%), Malassezia (8.3%) and Rhodotorula (8.2%).
Among the patients with respiratory illness, the second distinct sequence variant of the genus Cladosporium made up the nasal core microbiome with a prevalence of 90% and accounted for 12.8% of total reads. In the control group samples, no core mycobiomes were detected.
“The nasal mycobiomes were composed of basically two fungal groups (Ascomycota and Basidiomycota) and 14 genera, from which 71% were detected in a significantly higher frequency in allergy rhinitis than healthy controls,” Delgado said.
“Among these dominant genera, we detected common fungi (like Cladosporium, Alternaria, Penicillium, Aspergillus, Candida and Malassezia) that have been recognized in humans as allergenic and/or opportunistic fungi,” he continued.
Among the 14 dominant fungal genera, after false discovery rate correction, seven to 10 genera showed significant differences in mean relative proportions among all respiratory disease groups as well as the control group, although none of these genera varied significantly among the three respiratory groups.
Alpha-diversity indices of microbial community richness and evenness also varied among the groups. The indices varied significantly in the AR and AR with asthma groups compared with the control group (P .024). All the respiratory disease groups showed significant differences in beta-diversity compared with control group samples (P .0004). Participants in the AR and AR with asthma groups showed more similar interactions in Spiec-Easi fungal networks compared with the control group.
“Our study showed there are significant differences in the abundance of most of the top fungal taxa identified in the nasal passage of allergic rhinitis patients (with or without associated asthma), showing that the nasal mycobiota of healthy controls and rhinitis are compositionally and structurally distinct, encode different metabolic functions and establish different microbe-microbe connections among their members,” Delgado said.
He also explained that even though in both healthy and AR individuals, the nasal cavity is a major reservoir for allergenic or opportunistic fungi. According to Delgado, it should be noted that local or airways fungal infection and even fungal IgE sensitization/allergy are the exception, and not the rule, in the clinical presentation of AR and asthma in children.
Study implications
Delgado again emphasized that the role of fungal communities in the upper airways in rhinitis and asthma is practically unknown. He and his team explored the potential direct or indirect interactions among fungal groups and compared the structure and connectivity of the nasal mycobiome in the different patient groups.
“Interestingly, it was the group with rhinitis and comorbid asthma that showed a higher and more diverse mycobiome network with multiple positive and negative (competition) interactions among fungal taxa,” Delgado said. “Healthy controls and rhinitis patients showed fewer significant interactions, all of which were positive.”
He mentioned that previous research has shown that changes of the patterns of co-abundance and exclusion can be indicative of underlying disease processes that may be disrupting the “healthy” fungal connectivity and structure networks.
“These findings may have implications in the understanding of innate and adaptive host immune responses to fungi in the airways,” Delgado said. “Fungal cell wall components are known to interact with pattern recognition receptors on immune cells, leading to the activation of various immune pathways that can exacerbate or alleviate inflammation in the respiratory tract, influencing the severity of allergic reactions.”
The study results are minimally informative for causal inference, Delgado noted. This is due to the study outcomes and exposure being assessed at the same time point. The relevance of detecting fungi associated with specific phenotypes of airway diseases is still largely unknown, as well as its possible practical implications.
“It is still too early to propose that these ‘fungal footprints’ common to allergic rhinitis (with or without comorbid asthma) will have treatment implications,” Delgado said. “It is possible that the nasal mycobiome signatures we described might also serve in the future as biomarkers preceding the clinical manifestations of disease (e.g., the evolution of local disease, rhinitis, to the distant airways, as seen with comorbid asthma), or as an indicator for a specific therapeutical intervention.”
Future Research
Delgado said that future dual-transcriptomic studies that focus on Th2 and epithelial cytokines. Innate signaling with longitudinal sampling, as opposed to the cross-sectional sampling design used here, will also help to clarify whether specific microbes are drivers or bystanders in rhinitis and asthmatic patients.
“In this study we could not control all patient-specific variables, such as the time since the onset of symptoms, disease severity and related treatment levels and options, and patients were sampled at a single time,” he said. “Addressing clinical variables and deciphering fungal–bacterial interactions would be interesting follow-ups of our study.”
Reference:
Bousquet J, et al. Allergy. 2023;doi:10.1111/all.15679.
For more information:
Luis Delgado, MD, PhD, FAAAAI can be reached at ldelgado@med.up.pt.