Serena Chong ^1,2* Mike Lin ^3,4 Deborah Chong ⁵ Slade Jensen ^1,6 Namson S Lau ^1,2,7

• ¹ South West Sydney Limb Preservation and Wound Research, Ingham Institute of Applied Medical Research, Sydney, New South Wales, Australia
• ² South West Clinical School, Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia
• ³ Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
• ⁴ Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
• ⁵ Animal Health Laboratory - Department of Natural Resources and Environment Tasmania., Tasmania, Australia
• ⁶ Infectious Disease and Microbiology, Ingham Institute for Applied Medical Research, Sydney, Australia
• ⁷ Liverpool Diabetes Collaboration, Ingham Institute for Applied Medical Research, Sydney, Australia

Aims/Hypothesis The gut microbiota play crucial roles in the digestion and degradation of nutrients, synthesis of biological agents, development of the immune system, and maintenance of gastrointestinal integrity. Gut dysbiosis is thought to be associated with type 2 diabetes mellitus (T2DM), one of the world’s fastest growing diseases. The aim of this systematic review is to identify differences in the composition and diversity of the gut microbiota in individuals with T2DM. Methods A systematic search was conducted to identify studies reporting on the difference in gut microbiota composition between individuals with T2DM and healthy controls. Relevant studies were evaluated, and their characteristics and results were extracted using a standardised data extraction form. The studies were assessed for risk of bias and their findings were reported narratively. Results 58 observational studies published between 2010 and 2024 were included. Beta diversity was commonly reported to be different between individuals with T2DM and healthy individuals. Genera Lactobacillus, Escherichia-Shigella, Enterococcus, Subdoligranulum and Fusobacteria were found to be positively associated; while Akkermansia, Bifidobacterium, Bacteroides, Roseburia, Faecalibacteirum and Prevotella were found to be negatively associated with T2DM. Conclusions This systematic review demonstrates a strong association between T2DM and gut dysbiosis, as evidenced by differential microbial abundances and altered diversity indices. Among these taxa, Escherichia-Shigella is consistently associated with T2DM, whereas Faecalibacterium prausnitzii appears to offer a protective effect against T2DM. However, the heterogeneity and observational nature of these studies preclude the establishment of causative relationships. Future research should incorporate age, diet and medication-matched controls, and include functional analysis of these gut microbes.