The intestinal microbiome and metabolome discern disease severity in CTLA4 deficiency
What is already known on this topicCytotoxic T lymphocyte antigen 4 deficiency (CTLA4-D) is associated with a range of clinical complications centered around regulatory T cell dysfunction with variable disease penetrance. Extrinsic factors driving disease penetrance in CTLA4-D, including the intestinal microbiome have not yet been investigated.What this study addsWe present the first study of the intestinal microbiome and metabolome in patients with CTLA4-D. We have identified intestinal microbiome and metabolomic signatures that distinguish patients with CTLA4-D based on disease severity using 2 geographically distinct patient cohorts.How this study might affect research, practice or policyIdentified microbiome and metabolic biomarkers of CTLA4-D disease severity can be further investigated longitudinally to elucidate biomarkers that can predict progression to severe disease which would impact treatment planning, while also being functionally investigated as potential treatment targets.