| Objective: The oral cavity plays an important role in understanding the status or progression of HIV disease,but the pathogenesis mechanism of change in oral environment and oral lesions caused by HIV remains unclear at present. Metabolites present in the oral cavity are produced by both the host and microbes, and are likely to contribute to health and disease. Thus, profiling the oral metabolites will help to define the mechanisms underlying oral diseases in HIV-infected patients, to discover the new diagnostic targets for HIV status and to identify the novel biological markers HIV disease progression. To date, there are a few study has been performed to characterize oral metabolites in the background of HIV infection in developed countries, while research in this field has not yet conducted in China. This Project is to utilize case control study, as well as high-throughput metabolomic technology-liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), to compare the changing of oral metabolites in healthy control population with HIV-infected patients. The goal of this project is to investigate oral metabolite changes and evaluate its role as new potential biomarkers for early diagnosis, condition monitoring and treatment of HIV infection.Methods: Oral wash samples were collected from HIV-infected and healthy individuals (matched for age sex and ethnicity), processed, and analyzed its metabolomics by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry (GC - MS) respectively. Finally, the differential metabolites were screened out.Results: The oral wash samples of 30 HIV-infected patients who were not HAART were collected in the case group. And the CD4 + count was between 13.9-200 / m3 in the case group. In the control group, 30 oral wash samples of HIV-negative subjects were collected. After the detection of the two metabolomics methods, we confirmed that all the main components of all the sample were similar by PCA analysis and the HIV infection group had changes in saliva metabolism by OPLS-DA analysis. After screening, we found ten metabolic differences which are glucose, citric acid,phosphate, D-talose, galactose, D-erythronolactone and alpha-aminoadipic acid rising,while 1, 3-diaminopropane, 3-methyloxindole and 2-ketobutyric acid declining in the GC-MS detection. And nine metabolic differences were found in the LC-MS detection,including choline, L-citrulline, xanthine, 2-deoxynucleoside, thymidine, phosphoryl-choline, serine-Leucine increasing,while 3-Hydorxy-3-methylglutaric acid and L-gulonic gamma-lactone decreasing. Based on these metabolites, we thought the metabolic pathway of carbohydrate and the pathway of amino acid metabolism had changed in GC-MS. And the amino acid metabolic pathway, lipid metabolism pathway and nucleotide metabolic pathway detected by LC-MS had also been affected.By metabolic pathway analysis, we concluded that citric acid cycle, phosphate metabolism, valine, leucine and isoleucine biosynthesis, lysine biosynthesis and beta alanine metabolism might be affected in GC-MS and that caffeine metabolism,glycerophospholipid metabolism, arginine and proline metabolism, purine metabolism and pyrimidine metabolism may be affected in LC-MS.Conclusion: Metabolomics can be used to confirm that the salivary metabolism of HIV infection in the experimental group is obvious, but it can not be used as a diagnosed method with a single abnormal metabolic marker. However,a group of saliva biomarkers can be used to reflect the metabolic Changes of patients. Moreover,the research of different metabolomics methods can provide more comprehensive metabolic biology information. |
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