Circadian rhythms, which people sometimes refer to as the “body clock,” regulate patterns of sleep, alertness, temperature, and blood pressure, among other factors. These daily biological rhythms likely evolved to coordinate with light and food availability, but they also regulate internal metabolic processes.
Circadian rhythms are important to human health, and experts believe their long-term disruption to have various adverse consequences.
The possible health effects include obesity and type 2 diabetes. A growing body of evidence indicates a connection between circadian disruption and insulin resistance.
Building on this, a new study appearing in Cell Host & Microbe shows that diabetes is also associated with changes to the daily rhythms of the gut microbiome.
A team of researchers that the Technical University of Munich in Germany led showed that people with type 2 diabetes have fewer daily fluctuations in some of their gut bacteria and that these changes may serve to predict and diagnose the condition.
For many years, scientists have known that the circadian clock is crucial to human physiology. However, it is only recently that they have discovered its role in relation to the microbiome, which is the community of bacteria, viruses, and fungi that live in and on people — for instance, on the skin or in the gut.
Recent studies, for example, show that the community of gut bacteria fluctuates during the day, just like other circadian processes.
Some researchers believe that these regular changes to the microbiome are likely beneficial and that the loss of this daily rhythm could contribute to metabolic disorders, perhaps explaining the connection between circadian rhythms and diabetes.
To investigate this further, the team started by analyzing the microbiomes of almost 2,000 people over a period of 24 hours. Their results confirmed the regular oscillations of gut bacteria.
They then focused the study to include only the people with metabolic disorders, including obesity (defined as a body mass index, or BMI, of 30 or above), prediabetes, and type 2 diabetes.
They found that people with obesity and type 2 diabetes lost the rhythmic patterns of their gut bacteria. They also noted specific changes to the gut bacteria in people with diabetes.
Using a dataset of 2,039 people, the team started to detect particular changes to the microbiome that could serve as biomarkers to diagnose type 2 diabetes.
“When certain gut bacteria do not follow a day-night rhythm, so if their number and function does not change over the course of the day, this can be an indicator for [type 2 diabetes],”
– Silke Kiessling, co-author of the study
The researchers found 13 types of bacteria that did not change during the day in people with diabetes. They used these bacteria to train a mathematical model to detect whether a person has diabetes.
“Mathematical models also show that this microbial risk signature consisting of arrhythmic bacteria helps diagnosing diabetes,” explains first author Sandra Reitmeier.
When they tested the model on a new group of 699 people, it was able to predict not only who received a diagnosis of type 2 diabetes but also who was at risk of developing the condition.
The model was most effective in combination with BMI, which confirms the importance of obesity in diabetes onset.
“Apart from bacteria and their variations over the course of the day, other parameters, such as [BMI], play a role in being able to better predict a person’s future medical conditions,” adds senior author Prof. Dirk Haller.
The findings so far show a clear association between daily variations in the microbiome and type 2 diabetes, but they do not say anything about why the two are connected.
In the final part of their study, the researchers tried to answer this question by looking at changes to metabolism. They found 26 metabolic pathways that were associated with the lack of a microbial rhythm.
The same association existed for 19 of these pathways (73%) in a separate group of people with type 2 diabetes. These pathways included several that are known to influence sensitivity to insulin.
These common metabolic pathways suggest that the two states are functionally connected, although it is too early to say whether a disrupted microbiome actually causes diabetes.
While scientists do not yet fully understand the link between the microbiome and diabetes, the findings from this study suggest that a microbial risk score could be a new way to diagnose and predict the onset of type 2 diabetes.
