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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #294373
Title: Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups

Author
item GOO, YOUNG - University Of Washington
item CAIN, KEVIN - University Of Washington
item JARRETT, MONICA - University Of Washington
item SMITH, LYNNE - University Of Washington
item VOSS, JOACHIM - University Of Washington
item TOLENTINO, ERNIE - University Of Washington
item TSUJI, JOYCE - University Of Washington
item TSAI, YIHSUAN - University Of Washington
item PANCHAUD, ALEXANDRE - Nestle
item GOODLETT, DAVID - University Of Washington
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)
item HEITKEMPER, MARGARET - University Of Washington

Submitted to: Journal of Proteome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/21/2012
Publication Date: 12/7/2012
Citation: Goo, Y.A., Cain, K., Jarrett, M., Smith, L., Voss, J., Tolentino, E., Tsuji, J., Tsai, Y.S., Panchaud, A., Goodlett, D.R., Shulman, R.J., Heitkemper, M. 2012. Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups. Journal of Proteome Research. 11(12):5650-5662.

Interpretive Summary: Irritable bowel syndrome (IBS) is common in children and adults and causes stooling problems and abdominal pain. Different types of IBS exist but it is unclear what causes them. In this study, we used cutting edge technology to examine thousands of proteins present in the urine. We found that the amounts of certain proteins that take part in causing or preventing inflammation were altered in people with IBS compared to healthy people. These studies will help us understand better what causes the different types of IBS and address potential strategies to alleviate this issue.

Technical Abstract: Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with alterations in bowel function. Given the heterogeneity of the symptoms, multiple pathophysiologic factors are suspected to play a role. We classified women with IBS into four subgroups based on distinct symptom profiles. In-depth shotgun proteomic analysis was carried out to profile the urinary proteomes to identify possible proteins associated with these subgroups. First void urine samples with urine creatinine level=100 mg/dL were used after excluding samples that tested positive for blood. Urine from 10 subjects representing each symptom subgroup was pooled for proteomic analysis. The urine proteome was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a data-independent method known as Precursor Acquisition Independent From Ion Count (PAcIFIC) that allowed extended detectable dynamic range. Differences in protein quantities were determined by peptide spectral counting followed by validation of select proteins with ELISA or a targeted single reaction monitoring (LC-SRM/MS) approach. Four IBS symptom subgroups were selected: (1) Constipation, (2) Diarrhea+Low Pain, (3) Diarrhea+High Pain, and (4) High Pain+High Pychological Distress. A fifth group consisted of Healthy Control subjects. From comparisons of quantitative spectral counting data among the symptom subgroups and controls, a total of 18 proteins that showed quantitative differences in relative abundance and possible physiological relevance to IBS were selected for further investigation. Three of the 18 proteins were chosen for validation by either ELISA or SRM. An elevated expression of gelsolin (GSN) was associated with the high pain groups. Trefoil Factor 3 (TFF3) levels were higher in IBS groups compared to controls. In this study, the IBS patients subclassified by predominant symptoms showed differences in urine proteome levels. Proteins showing distinctive changes are involved in homeostasis of intestinal function and inflammatory response. These findings warrant future studies with larger, independent cohorts to enable more extensive assessment and validation of urinary protein markers as a diagnostic tool in adults with IBS.