Integrative Metagenomic Analysis Reveals Human Gut Microbiome-Derived Candidate Non-invasive Biomarkers for Type II Diabetes Mellitus

Abstract

Background: Type II Diabetes Mellitus (T2DM) is increasingly associated with alterations in the gut microbiome, which influences host metabolism, inflammation, and insulin sensitivity. Metagenomic profiling has emerged as a promising non-invasive strategy for identifying disease-associated microbial signatures. However, distinguishing disease-specific biomarkers from general dysbiosis remains a major challenge. This study aimed to develop an integrative subtractive metagenomic framework to identify candidate disease-specific gut microbial biomarkers. Methods: This in silico case-control study used publicly available metagenomics datasets from healthy controls and individuals with T2DM. Assembly-based and read-based taxonomic profiling approaches were integrated. Differential abundance analysis using the Wilcoxon rank-sum test identified key microbial taxa significantly associated with T2DM. Results: Potential microbial biomarkers were identified as Bacteroides dorei, Bacteroides gracilis, Bacteroides stercoris, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanisolvens, Eggerthella lenta, Escherichia coli, Faecalibacterium prausnitzii, Parabacteroides distasonis, Ruminococcus torques, and Subdoligranulum. These taxa are involved in gut metabolic homeostasis and may serve as candidate non-invasive biomarkers for T2DM. Conclusion: The results of this study advance understanding of microbiome-disease crosstalk and form the basis for further in vitro and in vivo validation and microbiome-targeted therapeutic approaches. Overall, this integrative metagenomic study supports alteration of microbial ecology in T2DM, validating the use of gut microbiome profiling as a diagnostic and therapeutic tool in metabolic disease research.