Monitoring type 2 diabetes from volatile faecal metabolome in Cushing’s syndrome and single Afmid mouse models via a longitudinal study

• Published in: Scientific reports 2019-12, Vol.9 (1), p.18779-13, Article 18779
• Main Authors: Lourenço, Célia, Kelly, Darren, Cantillon, Jack, Cauchi, Michael, Yon, Marianne A., Bentley, Liz, Cox, Roger D., Turner, Claire
• Format: Article
• Language: English
• Subjects: 631/1647/320; 64/60; 692/53/2422; 692/699/2743/137/773; Acetic acid; Adrenocorticotropic hormone; Animal models; Animals; Arylformamidase - genetics; Arylformamidase - metabolism; Blood glucose; Blood Glucose - metabolism; Cushing syndrome; Cushing Syndrome - diagnosis; Cushing Syndrome - metabolism; Data analysis; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - diagnosis; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - metabolism; Ethanol; Feces; Female; Gas chromatography; Gas Chromatography-Mass Spectrometry; Gastrointestinal Microbiome; Humanities and Social Sciences; Insulin - blood; Intestinal microflora; Longitudinal Studies; Male; Mass spectrometry; Metabolome; Mice; Mice, Knockout; Monitoring, Physiologic; multidisciplinary; Multivariate Analysis; Nervous system diseases; Obesity - metabolism; Organic compounds; Pituitary; Rodents; Science; Science (multidisciplinary); Scientific imaging; VOCs; Volatile organic compounds; Volatile Organic Compounds - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-55339-9

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.