The Gut Microbiome and ICS Response to Wheezing in Pediatric Asthma

The frequency of wheezing in children with asthma is linked to the fecal microbiome composition and taxa and thus may not be responsive to treatment with inhaled corticosteroids (ICS). This was among the findings of a study presented at the American Thoracic Society (ATS) 2022 Annual Meeting, held in San Francisco, CA, May 13 to 18.

In an ancillary study to the Vitamin D Antenatal Asthma Reduction Trial (VDAART; ClinicalTrials.gov Identifier: NCT00920621), researchers examined links between the gut microbiome, metabolome, and wheeze frequency in children with asthma using ICS. The researchers performed microbiome profiling via 16S rRNA gene sequencing and metabolomic profiling by mass spectrometry on fecal samples collected from 3-year-old children with asthma whose parents reported on their child’s ICS use on quarterly questionnaires on wheezing administered during the time their child was   aged 3 and 5 years. Only children whose parents responded to at least half of these questionnaires were included in this study.

The investigators then analyzed data from questionnaires in which parents reported childhood wheeze between ages 3 and 5 years. Links between bacterial taxa and wheeze were tested using the software program Songbird, which analyzes ratios between taxa to account for compositionality in microbiome data using multinomial regression models. Associations between metabolites and wheeze were evaluated in correlation, linear regression, and pathway analyses.

“In 28 ICS-treated participants, fecal microbial beta diversity (Bray-Curtis dissimilarity) at 3 years of age correlated with the frequency of wheeze between ages 3 and 5 years (PERMANOVA P =.03),” study authors reported. Further analysis showed global shifts in microbial composition between ICS nonresponders, in whom wheeze was reported on 50% or greater of questionnaires (n=13), and responders, in whom wheeze was reported on less than 50% of questionnaires (n=15). Fecal alpha diversity displayed a trend toward an inverse relationship with wheeze that was not significant.

Investigators further noted that “The log-ratio of the top 5 taxa positively linked with wheeze to the top 5 taxa negatively linked with wheeze in Songbird analysis correlated with wheeze frequency (Spearman rho=0.54, P =.005),” an association remaining after adjustment for potential confounders.

The Gram-negative diplococci, Veillonella, was positively associated most strongly with wheeze (ranked #1 of 43 genera). Of 737 analyzed fecal metabolites, 131 (17%) were nominally associated (P <.05) with wheeze frequency, and most (124 of 131, 95%) showed positive associations with wheeze. Sphingolipid metabolites were found to be enriched among ICS-treated children with more frequent wheeze (overrepresentation analysis P =.04).

“While the gut microbiome has an established role in asthma development, less is known about its contribution to steroid responsiveness in children with asthma,” the authors noted. “Our results suggest substantial perturbation to the fecal microbiome and metabolome in children who wheeze despite ICS treatment,” they reported.

Reference

Lee-Sarwar K, Dedrick S, Momeni B, et al. Association of the gut microbiome and metabolome with inhaled corticosteroid response in childhood asthma: a pilot study. Presented at: the American Thoracic Society 2022 International Conference; May 13 to 18, 2022; San Francisco, CA. Abstract A1020.

This article originally appeared on Pulmonology Advisor