Diabetes prevention: is Candida a good candidate?
There may be a window of opportunity during childhood when the enrichment of the microbiota with certain microorganisms, particularly Candida, is necessary for the development of pancreatic β-cells and, therefore, for the prevention of type 1 or type 2 diabetes and certain metabolic disorders.
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In zebrafish (Danio rerio), a bacterial protein promotes the proliferation of β cells in the islets of Langerhans. But what about mammals? Β-cells are necessary for sufficient insulin production, and their proliferation increases rapidly after birth, at the same time as the gut microbiota diversifies.
Is this a mere coincidence or is there a genuine correlation, as in zebrafish? A British team 1 has settled the question by showing in mouse pups that postnatal β-cell development is stimulated by bacterial and fungal species during short colonization windows, periods also critical for metabolic health.
830 million The number of people living with diabetes rose from 200 million in 1990 to 830 million in 2022. ²
14% In 2022, 14% of adults aged 18 years and older were living with diabetes, an increase from 7% in 1990. ²
In mice and humans
By eliminating and restoring microbiota at different pre- and postnatal periods in mouse pups, the team identified a critical period (from 10 to 20 days after birth) during which the gastrointestinal flora is essential for the establishment of a normal mass of β cells. These observations were confirmed by experiments with antibiotics and antifungals, highlighting the involvement of bacteria and fungi in maintaining glycemic balance.
These early alterations in the microbiota have lasting repercussions on metabolism, including decreased carbohydrate tolerance, elevated blood sugar levels, and reduced insulin secretion. All of these imbalances can increase the risk of diabetes.
And in humans? Fecal samples from human infants aged 7 to 12 months (but not from other age groups) strongly stimulated β-cell mass in mice. Humans therefore also appear to have a window of colonization by microorganisms that promote β-cells.
This is yet another argument in support of the much-publicized 1,000-day window of opportunity for future health and the prevention of metabolic diseases such as obesity.
59% More than half (59%) of adults aged 30 years and over living with diabetes were not taking medication for their diabetes in 2022. Diabetes treatment coverage was lowest in low- and middle-income countries. ²
2 million In 2021, diabetes and diabetes-related kidney disease caused over 2 million deaths. In addition, around 11% of cardiovascular deaths were caused by hyperglycemia. ²
Bacteria and fungi responsible
The comparison of microbial communities capable of inducing (or not) β-cell development has identified bacterial and fungal taxa involved in the case of mice: Escherichia coli, Enterococcus gallinarum, and Candida dubliniensis. The latter proved to be the most effective, thanks to a mechanism involving macrophages and β-cells, which allows the recognition of specific signals from the cell wall of commensal yeasts.
Lastly, not only does C. dubliniensis reduce the prevalence and severity of diabetes in mouse models, but it also helps restore the β-cell population after ablation or underdevelopment following antibiotic treatment. By disrupting gut microbiota during early childhood, these treatments can alter glycemic regulation and interfere with the maintenance of stable body weight. Could C. dubliniensis be used prophylactically to make up for losses induced by antibiotic treatment, particularly in individuals predisposed to type 1 or type 2 diabetes or obesity?
Since 2000
Mortality rates from diabetes have been increasing. By contrast, the probability of dying from any one of the 4 main non-communicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases or diabetes) between the ages of 30 and 70 decreased by 20% globally between 2000 and 2019. ²
In April 2021
WHO launched the Global Diabetes Compact, a global initiative aiming for sustained improvements in diabetes prevention and care, with a particular focus on supporting low- and middle-income countries. ²
Preventing or even reversing β cell loss?
This study shows that there may be a critical window in young children, between 7 and 12 months, during which certain bacteria and fungi are necessary for the development of β-cells in the pancreas. If this developmental window is missed, β-cell development may be compromised, leading to dysfunction and an increased risk of metabolic diseases such as obesity and diabetes.
However, the mechanisms identified by the authors of the study have the potential to prevent or even reverse the loss of β-cells, provided intervention comes early and takes into account the key role of the gut microbiota.
