Decoding the matrix: multiomics reveals host-microbe biomarker for inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine associated with genetic susceptibility and alterations in the intestinal microbiome. Multiomics data developed and analyzed over the last several decades have yielded an unprecedented amount of genetic and microbial data. But how do we pinpoint mechanistic insight into the host-microbe relationship that will ultimately enable better care for patients with IBD? In this issue of the JCI, Grasberger et al. undertook a major decoding effort to decipher this multiomic data matrix. The authors analyzed anonymized data from more than 2800 individuals to discover a link between heterozygous carriers of deleterious DUOX2 variants and high levels of plasma IL-17C. These findings provide an example of how harnessing big data can drive mechanistic discovery to define disease biomarkers that have the potential to improve clinical care in IBD.

Figure 1. Deleterious DUOX2 variants regulate barrier immunity and reveal IL-17C as a plasma biomarker of microbial dysbiosis in IBD.

In healthy individuals, production of hydrogen peroxide by DUOX2 promotes innate barrier immunity. In IBD patients with deleterious DUOX2 variants, a reduction in hydrogen peroxide allows for gram-negative penetration of the mucus barrier and induction of IL-17C secreted through the basolateral surface. IL-17C is increased in IBD patients with gram-negative dysbiosis and has the potential to serve as a biomarker of disease.