Abstract
Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds’ (VOCs) pattern when compared to controls. Patients 10–17 years of age, were divided into four groups: Crohn’s disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non–invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.
Highlights
Acetic Acid, systematically named ethanoic acid, is commonly used in animal Inflammatory bowel diseases (IBDs) models to reproduce an IBD condition. [42,43,44] Recent literature suggests that Acetic Acid and similar compounds are produced from pyruvic acid via pyruvate dehydrogenase, and that acetone
[45] It is commonly assumed that anaerobic metabolism is characterized by the non–specific production of fatty acids, such as acetic acid which is the product of several pathogens including Staphylococcus aureus
One of the products that are derived directly from acetic acid is acetaldehyde, systematic IUPAC name ethanal, that several reports identify as a significant marker of IBD. [30,47] Acetaldehyde is present in the intestinal colon and derives from an oxidative reaction caused by several pathogens
Summary
Inflammatory bowel diseases (IBDs), which comprise Crohn’s disease (CD) and Ulcerative Colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract that profoundly affect the quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world. [1,2,3,4,5] Around 25% to 30% of all diagnoses are made in the first two decades of life. [1,6] Among childhood onset-IBD, there is an especially rising incidence of CD that is approximately 3/100,000. [3] The prevalence in the pediatric population (< 20 years of age) is reported to be 58/100,000 for CD and 34/100,000 for UC. [4]Failure to diagnose and induce disease remission during the peri-pubertal period can have significant consequences such as missed pubertal growth spurt and reduced adult height, [7] or low bone mineral density leading to an increased long-term risk of fractures. [8]Patients with suspected IBD require a careful history and clinical examination along with blood tests. [6] Other ways of investigating the small bowel in CD are capsule endoscopy and magnetic resonance imaging. They can provide details about the extent of inflammatory changes in the mucosa and are able to identify smaller superficial mucosal lesions without radiation. Probert compared the VOCs profile in the headspace gas emitted from fecal samples from IBD patients, healthy subjects and patients with infectious diarrhea. He found a specific pattern of compounds strongly associated with the alteration of intestinal homeostasis. He found a specific pattern of compounds strongly associated with the alteration of intestinal homeostasis. [24] Another study demonstrated the potential application of fecal VOC analysis in diagnosing IBD in a pediatric cohort. [25] The headspace of urine in IBD patients showed a different VOC profile, with the suggestion that altered gut permeability is reflected in urinary profiles. [26]
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