Persistent Symptoms in Quiescent IBD

Overview

Even in the absence of inflammation, persistent symptoms in Crohn’s disease (CD) are prevalent and worsen quality of life. Amongst patients without inflammation (quiescent CD), we hypothesized that microbial community structure and function, including tryptophan metabolism, would differ between patients with (qCD+S) and without persistent symptoms (qCD-S).

Team

  • Jonathan Golob
  • Krishna Rao
  • Shrinivas Bishu
  • Allen Lee

Approach

We are employing a multi-omics approach to establish the mechanisms by which the gut microbiome contributes to persistent symptoms in quiescent CD. These include shotgun metagenomics and metabolomics.

Findings so far

Our first publication noted significant overrepresentation of microbes typically found in the mouth associated with persistent symptoms, specifically microbes associated with sulfidogenesis–or the ability to make energy from breaking down sulfur-containing materials.

Next steps

Sulfidogenesis results in the production of H2S. H2S, particularly at high levels, can poison mitochondria and therefore the ability of human cells to make energy. This opens the possibility of using a low-sulfur diet to reduce symptoms–a target of our ongoing efforts.

Much like with other mechanisms by which the microbiome has been established to contribute to poor outcomes, not all quiescent CD patients with persistent symptoms have a sulfidogenic signature. Thus, we expect a low-sulfur diet (and other targeting of sulfidogenesis by microbes) is most likely to be effective only in the subset of patients with this sulfidogenic signature. This is an opportunity to establish other mechanisms as well as target and optimize trials of anti-sulfidogenic interventions.

Avatar
Jonathan Golob, M.D., Ph.D.
Assistant Professor

A physician scientist interested in applying microbiome-trained AI/ML models to improve human hea