Abdominal pain-related functional gastrointestinal disorders (FGIDs; previously called Recurrent Abdominal Pain) affect 10-20% of children and adults worldwide exerting a tremendous economic, social, and emotional burden. Up to 66% of children go on to have similar symptoms as adults. In children, the two most common FGIDs are functional abdominal pain (FAP) and irritable bowel syndrome (IBS - essentially FAP with changes in stooling pattern). Management and treatment are hampered by lack of biomarkers to characterize and understand pathophysiologically what are phenotypically and arbitrarily defined conditions. Previous studies have evaluated IBS, not FAP, and relied primarily on retrospective symptom evaluation and utilized methodology (e.g., 16S sequencing) that limits in depth interrogation of perturbations (e.g., gut dysbiosis) reported in children and adults with IBS. Further, `omics (metabolomics, lipidomics, metaproteomics) data is largely missing from studies of FGIDs and is urgently required - our preliminary data show that it likely provides critical mechanistic insight into the links between abdominal pain symptoms and the pathobiologic alterations of gut dysbiosis, barrier dysfunction, and neuroimmune dysfunction which we and others have described in FGIDs. Our preliminary data support the hypothesis that these alterations can pathobiologically discriminate FGIDs from healthy controls as well as identify disease mechanisms of pain in FGIDs. We propose to build on our previous work and use previously collected prospective abdominal pain and stooling diaries and stool samples collected from a large and well-vetted group of children with FGIDs (IBS n=133, FAP n=47) and healthy controls (HC, n=112). Our Hypothesis is that microbial community characterization and `omics profiling will provide biomarkers to differentiate FGIDs (IBS and FAP) from HC and generate insight into the genesis of pain symptoms (and stooling characteristics in IBS).
Our Specific Aims are to use: 1) Global unbiased whole genome shotgun sequencing, metabolomics, lipidomics and metaproteomics (`omics) on stool samples to differentiate children with FGIDs vs HC using classifier models; Sub-Aim ? explore potential differences between FAP and IBS and HC; and 2) Proprietary Texas Children's Hospital Microbiome Center reference databases and state-of-the art bioinformatics approaches (e.g., supervised learning, bipartite, Bayesian models) to identify disorder-specific biomarkers and therapeutic targets within children with FGIDs: Sub-Aim 2a - Characterize the relationships between `omics and abdominal pain symptoms (and stooling symptoms in IBS). Sub-Aim 2b ? Characterize the relationships between `omics and abnormal physiology (impaired barrier function, neuroimmune dysfunction). It is anticipated that this innovative, multidisciplinary study will better inform patient management and offer unique therapeutic strategies based on novel insights provided by FGID biomarkers. The goals of this application fit with NINR PA- 18-140, the recently published NINR Symptom Science Model, and the NIH Common Fund and Precision Medicine Initiatives.

Public Health Relevance

Abdominal pain-related functional gastrointestinal disorders affect 10-20% of children and adults worldwide exerting a tremendous economic, social, and emotional burden. There is a critical need to understand what factors contribute to pain in these disorders so that effective management and treatment strategies can be designed. The results of this proposal will provide insight into the factors responsible for abdominal pain symptoms to allow better patient-specific treatment.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
Research Project (R01)
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Nursing and Related Clinical Sciences Study Section (NRCS)
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Matocha, Martha F
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Baylor College of Medicine
Schools of Medicine
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Chumpitazi, Bruno Pedro; McMeans, Ann Rhodes; Vaughan, Adetola et al. (2018) Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome. Clin Gastroenterol Hepatol 16:219-225.e1
Robin, Samantha G; Keller, Catherine; Zwiener, Russell et al. (2018) Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria. J Pediatr 195:134-139
Chumpitazi, B P; Kearns, G L; Shulman, R J (2018) Review article: the physiological effects and safety of peppermint oil and its efficacy in irritable bowel syndrome and other functional disorders. Aliment Pharmacol Ther 47:738-752
Chumpitazi, Bruno P; Lim, Jongbin; McMeans, Ann R et al. (2018) Evaluation of FODMAP Carbohydrates Content in Selected Foods in the United States. J Pediatr 199:252-255
Cruz, Ligia Alfaro; Kaul, Isha; Zhang, Yan et al. (2018) Assessment of Quality and Readability of Internet Dietary Information on Irritable Bowel Syndrome. Clin Gastroenterol Hepatol :
Varni, James W; Shulman, Robert J; Self, Mariella M et al. (2017) Gastrointestinal symptoms predictors of health-related quality of life in pediatric patients with functional gastrointestinal disorders. Qual Life Res 26:1015-1025
Hollier, John M; Czyzewski, Danita I; Self, Mariella M et al. (2017) Pediatric Irritable Bowel Syndrome Patient and Parental Characteristics Differ by Care Management Type. J Pediatr Gastroenterol Nutr 64:391-395
Chumpitazi, Bruno P; Weidler, Erica M; Czyzewski, Danita I et al. (2017) Childhood Irritable Bowel Syndrome Characteristics Are Related to Both Sex and Pubertal Development. J Pediatr 180:141-147.e1
Chumpitazi, Bruno P; Weidler, Erica M; Shulman, Robert J (2017) Lactulose Breath Test Gas Production in Childhood IBS Is Associated With Intestinal Transit and Bowel Movement Frequency. J Pediatr Gastroenterol Nutr 64:541-545
Varni, James W; Shulman, Robert J; Self, Mariella M et al. (2017) Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 23:704-711

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