How does the gut microbiome influence the airway?
Select figures from Wilson & Hernandez-Leyva et al. iScience 2023
A) V4-16S rRNA sequencing of MARS clinical stool samples with PERMANOVA analysis. B) NBC sample scores where vertical dashed lines represent donor samples used in mouse experiments. C) Schematic of germ-free mouse experiments where mice were colonized with healthy (H) or asthmatic (A) microbiomes before undergoing ovalbumin allergic airway inflammation (AAI). D) RNA sequencing on lung samples from healthy (HO) and asthmatic (AO) mice after AAI. E) BugFACS to sort IgA+ bacteria from IgA- where Bacteroides strains from the asthmatic microbiome were significantly more IgA-coated.
As part of the Microbiome and Asthma Research Study (MARS), we collected oral and nasal lavages along with stool samples from adults (18-40 years) and kids (6-10 years) with and without asthma.
To select pairs of healthy and asthmatic microbiomes to use in mouse studies, we created an NBC model to find representative samples and match demographics. Germ-free mice were then colonized with healthy or asthmatic gut microbiota from humans before undergoing allergic airway sensitization.
Mice that received an asthmatic microbiome had more lung oxidative stress and increased gut permeability.
Bacteroides fragilis strains in asthmatic microbiomes had increased IgA binding and were enriched with Bacteroides fragilis toxin (bft) compared to healthy microbiomes.
Colonizing mice with bft+ (ETBF) and bft- (NTBF) strains showed ETBF mice have increased gut permeability and altered lung inflammation.