Allergy is a global health problem, affecting more than 40% of the world population.
Allergy is often associated with a dysregulation of the immune system that becomes overactive
against allergens. Several genes are known to be important for the proper homeostasis of the
immune system in the epithelial tissues, and the loss of function of genes such as IKKß or SOX9
impacts the interaction between external stimuli and the host. Many of the allergic responses
are triggered through the regulatory cascade governed by transcriptional factor NF-κB.
Regulation of NF-κB activity is complex, involves several alternative routes, and is also
influenced by metabolites produced in the gut by resident microbes. In this study, we aimed to
profile small and large intestinal metabolite profiles in two mouse models of allergic disease,
and compare these profiles to those of wild type mice. Proton nuclear magnetic resonance was
used to acquire metabolite signatures of all samples.
Multivariate statistical analyses of the binned NMR data revealed that samples separated
into distinct groups corresponding to the gastrointestinal tract sections, and partially into groups
based on mouse model. Using NMR spectrum deconvolution, we also quantified levels of
twelve different metabolites known to be abundant in the gut lumen. Several quantified
metabolites such as butyrate, propionate, tryptophan, and threonine were significantly less
abundant in the gut of allergy disease mouse models compared to the wildtype mice. These
metabolites were previously shown to regulate the signaling pathways of NF-κB. Knocked out
the genes of IKKß or SOX9 in allergic mice models lowered the allergic responses in the
airways by increasing the production of immunoglobulin A.