A prospective clinical Brain-Gut natural history protocol has to date enrolled 97 participants of which 92 have completed the protocol. There are three measures of intestinal inflammation;fecal calprotectin, intestinal permeability, and serum cytokine IL-6 levels. Intestinal permeability is measured with the administration of a sugar based test solution which will be given orally to participants after an overnight fast. Excreted urine sugar ratios, expressed per m2 of body surface area measure gastrointestinal permeability. Serum IL-6 cytokine levels are measured via ELISA. Body mass and body fat analysis (plethysmography), intra-abdominal and liver ultrasound, and Fibroscan measures are collected. The intestinal permeability test solution was developed and tested and has been administered to 92 participants. The Gastrointestinal Pain Pointer (GIPP) is a technology that has been developed and beta tested, and validated at the Clinical Center of the NIH. The GIPP electronically gathers data on participants subjective location, type, and intensity of GI symptoms along with real-time synchronized objective measures of heart rate and blood pressure. The patient uses a graphical interface to choose their gender and body type, record the location and intensity of the GI distress, and selects descriptive words for the GI discomfort. This study found the GIPP to be a valid and reliable instrument thereby allowing clinicians to have a more integrated resource for pain assessment that includes location, intensity, and quality along with physiologic parameters (ref. 3) Recent findings include differential genetic expression in patients with differing digestive disorder symptoms (ref. 1, 5). An upregulation of the gene coding the pro-inflammatory cytokine IL-1a suggests that the mechansim behind stress-related changed in gastrointestinal symptoms is pro-inflammatory in nature (ref 4.) Additional findings were published regarding symptom distress in other comorbid digestive diseases including fatty liver disease. A structural equation model for patients with liver disease co-morbidities including HIV was tested, confirmed, and published (ref 2).

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