Changes in the composition of bacteria in the gut could provide early warning of type 2 diabetes (T2D), new research being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2) has found.
The analysis of data from hundreds of thousands of individuals identified hundreds of changes in the composition of the gut microbiome (the community of microorganisms that lives in the gastrointestinal tract) that can be detected before the onset of any changes in blood glucose measures.
This raises the possibility of using gut microbiome composition to help detect those at risk of type 2 diabetes and who may benefit the most from lifestyle changes. This could contribute to preventative approaches to support public health goals of reducing T2D diagnoses, say the study’s authors from Italy and the UK.
Currently, diabetes and prediabetes (where blood sugar levels are higher than normal but not high enough to be classed as diabetes) are diagnosed via tests (HbA1c, fasting plasma glucose and oral tolerance test) that look for higher levels of sugar in the blood.
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.
Major step forward
“These latest findings represent a major step forward in understanding how our gut microbiome is linked directly with metabolic disease,” explains Professor Tim Spector, Scientific Co-Founder of ZOE, and one of the study’s authors. “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.”
Previous studies have found strong links between T2D and the gut microbiome but they failed to consistently agree on the key bacteria across large populations.
To provide some clarity, 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 study involved 229,025 individuals (73.8% female, average age of 50 years). Some 3,627 had T2D and 14,022 had prediabetes. The remaining 211,376 were normoglycaemic, meaning they had a normal level of glucose in the blood.
Species of bacteria
The researchers identified 789 species of bacteria associated with T2D, when age, sex and BMI were factored in. Some 168 were present at higher levels in those with the condition and 621 at lower levels.
Examples include Enterocloster bolteae, which was more abundant in individuals with T2D. This species can form spores and has been previously associated with poorer cardiovascular and metabolic health. Another species, Romboutsia timonensis, was less abundant in T2D. This bacterium was only described in the last decade. Some of the other species were uncharacterised, meaning they have never been isolated or cultivated in a lab.
The changes were particularly pronounced in the individuals who were taking medication for T2D. However, they also occurred in those with T2D not taking medication.
Unmedicated diabetes
The team also found that 587 of the 789 species were associated with unmedicated prediabetes.
The researchers then investigated if the pattern, or signature, was present in people who did not have prediabetes or T2D but were at risk of developing it.
They did this by comparing the metagenomic data from 135,093 of the normoglycaemic individuals with blood sugar readings taken in the two hours after eating a meal. Blood sugar temporarily rises after eating. 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.
They found that individuals whose blood sugar remained high for longer than usual were more likely to have the pattern of gut bacteria seen in T2D. Across the study as a whole, the changes in the microbiome became more pronounced as insulin resistance increased.
Additional information
The researchers say that microbiome analysis should not be seen as a replacement for the standard tests used to diagnose T2D or prediabetes. Instead, the gut microbiome could offer additional information about a person’s risk of T2D, on top of well-known risk factors like sex, age, BMI and family history.
In addition, monitoring changes to the gut microbiome over time could provide people at risk of T2D with important feedback.
“We know that lifestyle changes, like diet and physical activity, can prevent or delay the onset of T2D,” explains Dr Baldanzi. “But people often struggle to notice these changes are working, beyond perhaps losing some weight. If we can detect early shifts in the gut microbiome and show someone they are on the right track, that could be a powerful source of motivation to keep going.”
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“It is important to underline that these results were enabled by the unprecedented size of ZOE’s cohort, as well as by the advances we developed in our laboratory in the computational methods needed to interpret metagenomic data,” adds Professor Nicola Segata, the study’s corresponding scientist.
“In fact, many bacterial species that are part of the diabetes signature are species that are currently completely uncharacterised and were identified by us for the first time directly from the metagenomic data. In other words, they are new to science.”
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