Gut-associated Metabolites and Diabetes Pathology: A Systematic Review

Katelyn Louise Gough^1,2*Samantha Dando^1,2,3Stephanie Teasdale^4,5Beatrix Feigl^3,6,7Flavia Huygens¹Elise Sarah Pelzer^1,2

• ¹School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia
• ²Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia
• ³Centre for Vision and Eye Research, Faculty of Health, Queensland University of Technology, Brisbane, Australia
• ⁴Queensland Diabetes and Endocrine Centre, Mater Hospital Brisbane, South Brisbane, Australia
• ⁵Mater Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
• ⁶School of Clinical Medicine, Faculty of Health, Queensland University of Technology, Brisbane, Australia
• ⁷Queensland Eye Institute, South Brisbane, Queensland, Australia

Background. As the global prevalence of diabetes mellitus reaches epidemic proportions, research into new therapeutic targets that address the underlying pathomechanisms of the disease is essential. Recent studies have elucidated the fundamental role of intestinal metabolic pathways in human health and disease processes and yet, the underlying cause of metabolic dysregulation in diabetes is largely unknown. Therefore, this systematic review aimed to identify the intestinal metabolomic profiles associated with gestational diabetes mellitus, type 1 diabetes mellitus, pre-diabetes mellitus, and type 2 diabetes mellitus. Methods. A systematic review of databases and grey literature repositories identified primary literature published between 2005 and 2022, that investigated patterns of human- and microbial-derived metabolite concentration in individuals with diabetes. Results. Data extracted from thirty-four eligible studies revealed 272 metabolites that were associated with diabetes diseases; the majority correlated with incidence of type 2 diabetes mellitus only. Inter-study discrepancies were reported based on the biospecimen type used in metabolomic analyses, namely blood, stool, or urine. Conclusion. The results of this review emphasise the paucity of research investigating gestational and type 1 diabetes mellitus intestinal metabolic perturbations. Furthermore, the potential for inter-study bias in downstream metabolomic analyses based on sample type warrants further investigation.