The gut microbiome and asthma in a Swedish twin study

Lachnospiraceae taxa showed more phylogenetic diversity, and were mostly DA for asthma-only, followed by allergic asthma and the IgE + −allergic group. Ruminococcoceae taxa were mostly DA for asthma-only and the IgE + allergic group, with some phylogenetic separation between the two groups of taxa. Species from Bacteroidaceae were mostly DA for allergic asthma, followed by asthma-only and IgE + allergic. We found little systematic evidence for non-additive contributions from raised IgE and non-allergic asthma to DA in allergic asthma. In conclusion, we found no evidence for differences in the over-all gut microbial richness or composition between healthy controls and children diagnosed with allergic asthma, asthma only or IgE sensitization only. The combined activity of raised IgE and asthma on the differential abundance in allergic asthma was almost exclusively additive, with no systematic evidence for synergistic or antagonistic effects. Additional information on this study is published on Zenodo: https://doi.org/10.5281/zenodo.7998496.


R E S E A R C H L E T T E R The gut microbiome and asthma in a Swedish twin study
To the editor, Asthma studies have naturally focused on the airway microbiome, however, some studies support the hypothesis that the onset of allergic disease, lies partly in the microbial communities in the gastrointestinal tract, with asthma and taxa-specific shifts in the abundance of specific bacteria being interrelated. 1Our aim was to study the association between the gut microbiome and allergic asthma in a well-characterized Swedish cohort of twin children aged from 9 to 14.
We conducted a population-based study of Swedish twin children recruited from the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) cohort. 2 Per protocol, twins completed written standardized questionnaires and participated in clinical examinations where blood and faecal samples were collected. 2cruitment was based on informed consent received from both children and their parents/guardians and approval from the Swedish Ethical Review Authority.
We defined allergic asthma as a composite outcome based on parental response to the question of current asthma (yes/no) and/or wheezing within the last 12 months (yes/no) 3 and a raised serum IgE level of ≥0.35 kU A /L. 4 Those with a raised IgE level but no asthma were classified as IgE+ sensitized, while children with neither asthma nor raised IgE levels (IgE+) were included as healthy controls.In total, 355 individual children provided faecal samples, and these were processed using shotgun sequencing.

34.9%), respectively.
After rarefaction to 1 × 10 6 reads for each of the 339 samples, alpha-and beta-diversity measures were calculated and the n = 317 samples with non-missing exposure information were used for comparing diversity between exposure groups. 5We found no statistically significant evidence for differences in within-sample alpha diversity between exposure groups, either before (Shannon: p = .39,Simpson: p = .29)or after adjustment for shared twin effects (Shannon: p = .59,Simpson: p = .33).Furthermore, there was no statistically significant evidence for differences in overall species composition between exposure groups in unadjusted analyses, for either phylogenetically informed measures (weighted and unweighted UniFrac distance 6 ) or the Bray-Curtis dissimilarity: asthma/allergy phenotypes explained approximately 1% of variability in microbial community composition for all three beta-diversity measures.After adjustment for sequencing run, geographical sampling site and shared twin effects, the amount of variability was reduced to 0.5-0.8%,with marginal significance for the Bray-Curtis dissimilarity, but no statistical significance for the UniFrac distances, providing little or no evidence for systematic differences in species composition between asthma phenotypes.The largest explanatory factor for microbial composition, regardless of diversity measure, was twin pair (R 2 = 66-71%, all p = .001).In contrast, geographical sampling site and sequencing run jointly explained less than 5% of variability.
Running ANCOMBC 7 on the quality-filtered data with an extra 50% prevalence filter provided inference for 1969 species, corresponding to 93% of all quality-filtered reads.In total, 201 of the 1969 assessed taxa (10%) were statistically significantly differentially abundant (DA) between the healthy control group and at least one of the three exposure levels at an FDR level ≤1%.

Figure 1A .
Figure 1A.We found that the eight most common microbial families among all DA taxa covered 77% of DA taxa, compared to 70% for taxa DA for asthma alone, and 82% for IgE+ allergy and allergic asthma DA taxa.Similarly, the four most common families (Streptococcaceae, Lachnospiraceae, Ruminococcoceae and Bacteroidaceae) alone already accounted for 68% (pooled across exposures), 56% (asthma alone), 75% and 77% (IgE+ allergic and allergic asthma, respectively) of all taxa DA in their category.However, the actual distribution of families within each exposure level differed widely, with the proportions of DA Streptococcaceae and Lachnospiraceae taxa more similar between the IgE+ allergic-and allergic asthma groups, and the proportion of DA Ruminococcoceae and Bacteroidaceae more similar between the asthma-alone-and IgE+ allergic groups.The overall most common This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.© 2023 The Authors.Clinical & Experimental Allergy published by John Wiley & Sons Ltd.