title: Analysis of the effects of microbiome-related confounding factors on the reproducibility of the volatolomic test.
abstract: Volatile organic compound (VOC) testing in breath has potential in gastric cancer (GC) detection. Our objective was to assess the reproducibility of VOCs in GC, and the effects of conditions modifying gut microbiome on the test results. Ten patients with GC were sampled for VOC over three consecutive days; 17 patients were sampled before and after H. pylori eradication therapy combined with a yeast probiotic; 61 patients were sampled before and after bowel cleansing (interventions affecting the microbiome). The samples were analyzed by: (1) gas chromatography linked to mass spectrometry (GC-MS), applying the non-parametric Wilcoxon test (level of significance p  <  0.05); (2) by cross-reactive nanoarrays combined with pattern recognition. Discriminant function analysis (DFA) was used to build the classification models; and leave-one-out cross-validation analysis was used to classify the findings. Exhaled VOCs profiles were stable for GC patients over a three day period. Alpha pinene (p  =  0.028) and ethyl acetate (p  =  0.030) increased after the antibiotic containing eradication regimen; acetone (p  =  0.0001) increased following bowel cleansing prior to colonoscopy. We further hypothesize that S. boulardii given with the standard eradication regimen to re-establish the gut microbiome was the source for long-term ethyl acetate production. Differences between the initial and the follow-up sample were also revealed in the DFA analysis of the sensor data. VOC measurement results are well-reproducible in GC patients indicating a useful basis for potential disease diagnostics. However, interventions with a potential effect on the gut microbiome may have an effect upon the VOC results, and therefore should be considered for diagnostic accuracy.
authors.affiliation: Faculty of Medicine, University of Latvia, 19 Raina Blvd, Riga, LV 1586, Latvia. Department of Research, Riga East University Hospital, Linezera street 6, Riga, LV 1006, Latvia. Digestive Diseases Centre GASTRO, Linezera street 6, Riga, LV 1006, Latvia. Authors contributed equally to the work.
authors.forename: Marcis
authors.initials: M
authors.lastname: Leja
authors.forename: Haitham
authors.initials: H
authors.lastname: Amal
authors.forename: Ieva
authors.initials: I
authors.lastname: Lasina
authors.forename: Roberts
authors.initials: R
authors.lastname: Skapars
authors.forename: Armands
authors.initials: A
authors.lastname: Sivins
authors.forename: Guntis
authors.initials: G
authors.lastname: Ancans
authors.forename: Ivars
authors.initials: I
authors.lastname: Tolmanis
authors.forename: Aigars
authors.initials: A
authors.lastname: Vanags
authors.forename: Juozas
authors.initials: J
authors.lastname: Kupcinskas
authors.forename: Rima
authors.initials: R
authors.lastname: Ramonaite
authors.forename: Salam
authors.initials: S
authors.lastname: Khatib
authors.forename: Shifaa
authors.initials: S
authors.lastname: Bdarneh
authors.forename: Rasha
authors.initials: R
authors.lastname: Natour
authors.forename: Areen
authors.initials: A
authors.lastname: Ashkar
authors.forename: Hossam
authors.initials: H
authors.lastname: Haick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001944:Breath Tests / Q000379:methods*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008297:Male; D064307:Microbiota / Q000235:genetics*; D008875:Middle Aged; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D055549:Volatile Organic Compounds / Q000032:analysis / Q000378:metabolism*
chemical_list: D055549:Volatile Organic Compounds