The relationship between the early life gastrointestinal microbiome and childhood nocturnal cough.

Background: Nocturnal cough affects approximately 1 in 3 children, can negatively impact child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated.

Objective: To investigate the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma.

Methods: Gut microbiota 1-month (neonate) and 6-month (infant) specimens from 512 children in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study were profiled using 16S rRNA V4 sequencing. Nocturnal cough (parental-report) and asthma (parental-reported doctor diagnosis) were assessed at age 4 years. Microbiome Regression-Based Kernel Association Tests were used to assess the relationship between gut microbiota composition and nocturnal cough overall and in the context of asthma. Operational taxonomic unit (OTU) associations were conducted using negative binomial regression, adjusting for multiple comparisons using the false discovery rate (FDR).

Results: Stool microbial composition differences during infancy were associated with nocturnal cough (Weighted Unifrac p=0.045). 78 OTUs were significantly associated with nocturnal cough overall (FDR<0.05). 110 OTUs were significantly associated with nocturnal cough and differed by asthma status (interaction FDR<0.05), with predominance of Lachnospiraceae Blautia and Dorea. 32 OTU were identified as having both overall effects and differences by asthma status. Among OTUs with significant nocturnal cough-by-asthma interactions, 84 retained significance in children with asthma, with 45 exclusive to those with asthma (predominance of Bacteroidaceae Bacteroides and Lachnospiraceae Dorea).

Conclusion: Infantile gut microbiome development is associated with nocturnal cough and differed by asthma status by age 4 years. Further studies are needed to determine if the gut microbiome may provide additional information for the early identification of children at risk for nocturnal cough, with and without asthma.