Integrative analysis of molecular expression from blood of chronic abdominal pain and weight phenotypes provides differential clinical profiles for translational research

Authors

• JM Robinson
• C Boulineaux
• S Turkington
• NH Fourie
• WA Henderson

Abstract

Chronic abdominal pain (CAP) and Irritable Bowel Syndrome (IBS) are among the most common gastrointestinal disorders in the United States. Obesity is also commonly associated with increased risk for chronic abdominal pain. Likewise, molecular and cellular responses in obese individuals exhibit hallmarks of inflammatory activation. To better understand these interactions, we undertook collection and integration of blood RNA expression and complete blood count (CBC) data, collected at the NIH Clinical Research Center under the Brain-Gut Natural History Clinical Protocol. Participants were classified as 1) no CAP/normal weight, 2) CAP/normal weight, 3) CAP/normal weight, and 4) CAP/overweight. IBS positive individuals were subtyped as IBS-D or IBS-C (diarrhea and constipation predominant respectively). CBC data was obtained through the Clinical Center Department of Laboratory Medicine; RNA was extracted in the Henderson Lab from samples from whole blood and buffy coat from the same cohort. The Nanostring nCounter® system was used to obtain multiplexed expression data for 800 mature microRNAs from whole blood and 250 stress- and inflammation-associated coding genes from PBMCs. Datasets were integrated and analyzed with multivariate statistical methods, which indicated significant differences between IBS-subtypes of normal vs. healthy weight categories. These include differential CBC and serum protein inflammation markers, differential whole-blood miRNA expression, and differential PBMC gene expression, specifically for genes associated with regulation of monocyte activation. Normal weight healthy vs. IBS participants showed significantly divergent profiles compared with overweight counterparts, providing novel putative biomarkers and improved resolution of the effects of weight on the underlying pathology of common gastrointestinal pain disorders.

Scientific Focus Area: Systems Biology

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