Chronic inflammation of the gastrointestinal (GI) tissues underlies GI inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These GI disorders include inflammatory bowel diseases (Crohn’s disease (CD) and ulcerative colitis (UC)), and eosinophilic disorders (eosinophilic esophagitis (EoE) and eosinophilic duodenitis (EoD)). GI inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give a proper diagnosis. This study aims to use peripheral blood mononuclear cells (PBMCs) from individuals with CD, UC, EoE, and EoD to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing (scRNA-seq) was performed on PBMCs isolated from the blood samples of pediatric patients diagnosed with a GI disorder, including CD, UC, EoE, EoD, and controls with histologically healthy gastrointestinal tracts. We identified 1,185 (FDR < 0.05) differentially expressed genes (DEGs) between individuals with GI disorders and controls across six distinct immune cell populations. Few patterns of gene dysregulation were common among all GI disorders, including the downregulation ofESR2in CD4+T cells compared to controls. Many DEGs showed distinct patterns of dysregulation among individuals with CD, UC, EoE, and EoD compared to controls, such as dysregulation of genes associated with oxidative stress in monocytes of individuals CD and the upregulation ofSCGB3A1in CD4+T cells in individuals with EoD. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with CD, UC, EoD, and EoE compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.
