Stage-specific gut microbiome shifts across the Type 2 Diabetes Mellitus spectrum: A systematic review and meta-analysis
Abstract
Abstract Aims: The gut microbiome has been implicated in type 2 diabetes progression, but reproducible biomarkers across studies remain limited due to technical and population heterogeneity. This study investigated whether specific gut microbiome shifts occur progressively across stages of type 2 diabetes. Methods: We systematically reanalysed 16S rRNA datasets from 12 published studies (n=1,247 samples) after quality control, examining five groups (healthy controls, prediabetes (PD), new onset type 2 diabetes, established type 2 diabetes, and type 2 diabetes with complications. Sequencing reads were quality filtered, denoised, and resolved into amplicon sequence variants with genus level taxonomic assignments using the SILVA database. Centered log-ratio (CLR) transformed abundance data were analysed using PERMANOVA, meta-analysis with leave one study out validation, differential abundance testing (Wilcoxon and ANCOM), and Random Forest classification. Eligible studies were identified through comprehensive searches of PubMed, Ovid Medline and Web of Science from June 2010 June 2025 using predefined inclusion and exclusion criteria following PRISMA 2020 guidelines. Studies were investigated by two independent reviewers and included if they provided 16S rRNA data on adults across diabetes stages. Study quality was assessed based on metadata completeness and raw data availability. This systematic review and meta analysis was registered in the Open Science Framework (OSF;…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,247 participants or records.
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