Researchers analyzing data from over 200,000 adults in the UK and US have identified hundreds of specific gut microbiome changes associated with type 2 diabetes. The findings, presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2), reveal microbial signatures that appear before blood glucose levels rise.
Microbial Signatures and Blood Sugar Levels
Changes in the composition of bacteria in the gastrointestinal tract could provide an early warning of type 2 diabetes according to new research presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2). The analysis evaluated data from 229,025 individuals, which included 3,627 people with type 2 diabetes, 14,022 with prediabetes, and 211,376 normoglycaemic individuals who maintained normal blood glucose levels. The study participants had an average age of 50 years, and 73.8% of the cohort were female.
The research team identified 789 species of bacteria associated with type 2 diabetes after factoring in age, sex, and body mass index. Among these, 168 species appeared at higher levels in individuals with the condition, while 621 species appeared at lower levels. For instance, Enterocloster bolteae was more abundant in participants with type 2 diabetes. This spore-forming species has previous links to poorer cardiovascular and metabolic health. Conversely, Romboutsia timonensis—a bacterium described only within the last decade—was less abundant in those with the condition. The analysis also noted that many other species remained uncharacterized, meaning they have never been isolated or cultivated in a laboratory setting. The team also found that 587 of the 789 species were associated with unmedicated prediabetes.
Detecting Risk Before Glucose Rises
Standard clinical diagnostics rely on tests like HbA1c, fasting plasma glucose, and oral tolerance test to catch elevated sugar levels. However, these tests aren’t used to flag up people with normal levels of blood sugar who are at risk of developing T2D in the future. Instead, risk is currently assessed by looking at factors like age, sex BMI and family history.
To determine if microbial patterns could spot risk earlier, researchers examined metagenomic data from 135,093 of the normoglycaemic individuals alongside blood sugar readings taken in the two hours after eating a meal. When blood sugar temporarily rises after eating, and if it remains high, this is usually a sign that the muscles are not responding well to insulin – insulin resistance – an early step on the path to T2D. The analysis showed that individuals whose post-meal blood sugar stayed elevated longer than usual were more likely to harbor the gut bacteria pattern characteristic of the disease. Overall, microbiome changes became more pronounced as insulin resistance increased.
Dr Gabriel Baldanzi, of the Laboratory of Computational Metagenomics, and Professor Nicola Segata, who leads the lab at the CIBIO Department, University of Trento, Trento, Italy, and colleagues in the UK examined metagenomic data (the DNA sequences of the bacteria living in the gut) and health information from more than 200,000 adults in the UK and US.
The researchers emphasize that microbiome analysis is not intended to replace standard diagnostic blood tests. Rather, the gut microbiome could offer additional information regarding a person’s metabolic risk on top of established factors.
Investigating Microbiome Maturation and Host Genetics
Prospective cohort investigations, such as the TEDDY study funded by the National Institutes of Health (NIH), have tracked infants from early life to examine environmental causes of T1D. Between September 2004 and February 2010, the study screened 424,788 newborns who were younger than 4 months across six clinical research centres: three in the United States (Colorado, Georgia/Florida and Washington) and three in Europe (Finland, Germany and Sweden).
Among those screened, 21,589 had HLA genotypes associated with an increased risk of T1D, and the parents of 8,676 infants consented to participate in the follow-up study. A related international effort, the DIABIMMUNE three-country cohort, included 212 infants recruited from Finland (n = 71), Estonia (n = 71) and Russia (n = 70), countries with substantial differences in T1D and allergy incidence, with monthly stool samples collected. These prospective studies examine how early-life microbial colonization patterns interact with genetic backgrounds to influence disease trajectories.
Implications for Public Health Interventions
The identification of hundreds of microbial shifts before glucose alterations occur opens new avenues for preventative health strategies. Investigators note that identifying these clear microbial changes before blood sugar levels worsen could lead to earlier intervention with food and lifestyle choices, as well as treatment options, to prevent T2D, contributing to preventative approaches to support public health goals of reducing T2D diagnoses, say the study’s authors from Italy and the UK.
Professor Tim Spector, one of the study’s authors, Scientific Co-Founder, ZOE, highlighted that identifying these microbial changes early could lead to proactive interventions. Monitoring microbiome shifts over time may also give individuals tangible feedback on whether their lifestyle modifications are altering their underlying microbial profile, addressing a common challenge where patients struggle to perceive if behavioral changes are working beyond simple weight loss.
