New insights on the microbiome’s impact on diabetes pathogenesis create future pathways for diagnosis.
Gut microbiome functional shifts have been linked to type 2 diabetes, with particular species being identified as potential biomarkers by the MicroCardio Consortium research team.
Analysing over 8000 metagenomes of individuals with type 2 diabetes, prediabetes and normoglycemic status across 10 cohorts in the US, Europe, Israel and China, researchers identified 19 phylogenetically diverse microbial species that were significantly associated with type 2 diabetes.
Compared to normoglycemic patients, there was a notable shift away from glucose homeostasis in type 2 diabetes patients, moving instead towards the production of glycolysis-favouring enzymes and enhanced pathways for detoxifying glycolysis byproducts.
Notable biomarkers included E. coli, Bacteroides spp., Prevotella copri, Coprococcus comes, and Blautia wexlerae. Their altered functions were associated with crucial aspects of type 2 diabetes pathogenesis such as glucose metabolism, immune modulation and the production of inflammatory molecules.
They also found that genes encoding the enzyme pitrilysin for insulin degradation were more abundant in type 2 diabetes patients, and synthesis pathways of pro-inflammatory lipopolysaccharides and teichoic acids were enriched. The microbiota of type 2 diabetes patients exhibited greater virulence, resilience in adverse conditions and antibiotic resistance.
The study highlighted the significant influence of metformin on these microbial associations, notably that those being treated with it had an increased abundance of Akkermansia muciniphila. They also found that species such as Clostridium bolteae and Butyrivibrio crossotus could be useful biomarkers as they were either enhanced or diminished in type 2 diabetes patients.
These associations were independent of risk factors and confounders such as age, sex and BMI. Sensitivity analysis confirmed that long-term diabetic status and comorbidities did not change the findings.
The gut microbiome is increasingly being recognised for its influence on type 2 diabetes. Previous studies in this area have been hindered by small populations and lack of adjustment for type 2 diabetes risk factors, despite type 2 diabetes affecting approximately 537 million people across the globe.
Researchers concluded that while the study does not establish causal linkages, it offers the most comprehensive evidence to date of the gut microbiome’s involvement in the pathogenesis of type 2 diabetes and identifies functional biomarkers as a future diagnostic tool.
