SFC-IgG-seq in IBD

Title: Systemic IgG prunes gut microbiota ecology in inflammatory bowel disease. The gut microbiota is significantly altered in people with inflammatory bowel disease (IBD), most notably exhibiting a depletion of key health-associated gut bacteria that produce short chain fatty acids (SCFA) including butyrate. Given the capacity for butyrate to dampen inflammation and support gut epithelial integrity, the relative depletion of SCFA-producing bacteria in IBD is thought to be a significant contributor to disease. However, the mechanisms by which microbial dysbiosis occurs in this condition remain unknown1. Using two longitudinal human cohorts, we find that SCFA-producing bacteria are prominent targets of systemic IgG in IBD and that this phenomenon precedes Crohn's disease diagnosis by up to 6 years. Both IgG and neutrophils enter the gut lumen in IBD patients, a process that associates with disease severity, decreased bioavailable SCFA, and depletion of IgG-targeted gut bacteria including, most notably, SCFA producers. In murine models of gut barrier disruption, anti-commensal systemic IgG causes gut microbe-specific depletion that is dependent on neutrophils and Fc? receptors. When IgG is directed at SCFA-producing gut bacteria, this phenomenon leads to SCFA depletion in the host, suggesting a causal framework for the observed associations in humans. We uncover a method by which host immunity prunes gut microbiota ecology in the setting of gut barrier disruption and highlight a role for IgG and neutrophils in the depletion of protective SCFA-producing gut bacteria in IBD, which may inform strategies to reverse dysbiosis in IBD. Contact: Ivan Vujkovic-Cvijin. This submission was powered by METAGENOTE (https://metagenote.niaid.nih.gov).