Abstract
The analysis of volatile organic compounds (VOCs) as a non-invasive method for disease monitoring, such as type 2 diabetes (T2D) has shown potential over the years although not yet set in clinical practice. Longitudinal studies to date are limited and the understanding of the underlying VOC emission over the age is poorly understood. This study investigated longitudinal changes in VOCs present in faecal headspace in two mouse models of T2D – Cushing’s syndrome and single Afmid knockout mice. Longitudinal changes in bodyweight, blood glucose levels and plasma insulin concentration were also reported. Faecal headspace analysis was carried out using selected ion flow tube mass spectrometry (SIFT-MS) and thermal desorption coupled to gas chromatography-mass spectrometry (TD-GC-MS). Multivariate data analysis of the VOC profile showed differences mainly in acetic acid and butyric acid able to discriminate the groups Afmid and Cushing’s mice. Moreover, multivariate data analysis revealed statistically significant differences in VOCs between Cushing’s mice/wild-type (WT) littermates, mainly short-chain fatty acids (SCFAs), ketones, and alcohols, and longitudinal differences mainly attributed to methanol, ethanol and acetone. Afmid mice did not present statistically significant differences in their volatile faecal metabolome when compared to their respective WT littermates. The findings suggested that mice developed a diabetic phenotype and that the altered VOC profile may imply a related change in gut microbiota, particularly in Cushing’s mice. Furthermore, this study provided major evidence of age-related changes on the volatile profile of diabetic mice.
Highlights
Volatile organic compounds (VOCs) are produced as a consequence of endogenous metabolic activities and these can potentially be used as an alternative non-invasive approach to assist in the diagnosis or in monitoring the progress of disease
Selected ion flow tube mass spectrometry (SIFT-MS) and thermal desorption coupled to gas chromatography-mass spectrometry (TD-GC-MS) have been widely used for untargeted analysis, and when combined these techniques provide a powerful approach for the detection and identification of metabolites in a biological sample[22,23,24,25,26]
In the present study we investigated the longitudinal changes in volatile faecal metabolites in mouse models of diabetes acquired either by selected ion flow tube mass spectrometry (SIFT-MS) and TD-GC-MS
Summary
Volatile organic compounds (VOCs) are produced as a consequence of endogenous metabolic activities and these can potentially be used as an alternative non-invasive approach to assist in the diagnosis or in monitoring the progress of disease. Gut microbiota are thought to influence glucose and energy metabolism through the production of short-chain fatty acids (SCFAs) These volatile SCFAs include butyric acid, acetic acid, propionic acid, formic acid, isobutyric acid, valeric acid, isovaleric acid, and caproic acids, acetate, propionate and butyrate make up 90 to 95% of SCFAs within the gut[7,8]. The mouse model of Cushing’s syndrome used in this study is a N-ethyl-N-nitrosourea (ENU) chemically induced point mutation in the Crh promoter (the point mutation is inherited) and is a model with many of the features of type 2 diabetes[18] These Cushings mice develop excessive circulating glucocorticoid concentrations in the body. The Afmid knockout mice have been used to further investigate possible links between abnormal tryptophan metabolism and diabetes The phenotype of these mice include a defect in glucose stimulated insulin secretion and reduced islet mass with age. These mice show impaired glucose tolerance, their insulin sensitivity is unchanged when compared to wild-type (WT) animals[6,21]
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