The Fecal Microbiota Profile and Bronchiolitis in Infants

Abstract

Background: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants.

Methods: We conducted a case-control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis.

Results: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58-15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56-12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile.

Conclusions: In this case-control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis.

FIGURE 1

Clustering and composition of fecal microbiota in 155 infants. All fecal microbiota profiles of cases and controls were clustered via partitioning around medoids clustering method with Bray–Curtis distance. Colored bars indicate 4 microbiota profiles: Escherichia-dominant profile (ESP; red), Bifidobacterium-dominant profile (BFD; green), Enterobacter/Veillonella-dominant profile (EVP; blue), and Bacteroides-dominant profile (BCP; purple). The optimal number of clusters was identified by use of the gap statistic. To obtain additional information about the bacterial composition of samples within microbiota profiles, the 10 most abundant genera present in an adjacent heatmap were displayed. The taxonomy depicted is on the genus level because our sequences were dominated by 1 OTU per genus.

FIGURE 2

Nonmetric multidimensional scaling (NMDS) ordination of fecal microbiota. The Bray–Curtis distance between all cases and controls was calculated and used to generate nonmetric multidimensional scaling plots. Each dot in the figure represents the microbiota profile of a single subject in a low-dimensional space. Colored dots indicate 4 microbiota profiles: Escherichia-dominant profile (red), Bifidobacterium-dominant profile (green), Enterobacter/Veillonella-dominant profile (blue), and Bacteroides-dominant profile (purple). The subjects cluster together according to their microbiota profiles.

FIGURE 3

Effect sizes of genera that were significantly associated with likelihood of being a case (bronchiolitis) or healthy control. The linear discriminant effect size method was used to compare the abundances of all detected bacteria between cases and controls, computing an effect size for each comparison. Results shown here are significant by Kruskal–Wallis test (Benjamini–Hochberg adjusted P < .05) and represent large differences between groups (absolute effect size >3.6). Positive values (right) correspond to the effect sizes representative of healthy infants (controls), and negative values (left) correspond to the effect sizes infants with bronchiolitis (cases). Veillonella genus was found to be overrepresented in healthy infants, whereas Bacteroides genus was overrepresented in infants with bronchiolitis.