Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Introduction: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with ( Methods: We performed a multi-center observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level <150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD ( Results: Thirty-nine patients with qCD+S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD+S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD+S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD+S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H Discussion: Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD+S, which implicate H Key Messages: