Microbiota Cathelicidins May Protect Against Type 1 Diabetes Development

Your body has ten times the amount of microbes than human cells. This set of bacteria is called microbiota. In some cases, bacteria known as pathogens can cause infectious diseases, but these micro-organisms can also protect us from certain diseases.

Recently, how microbiota protects against the development of type 1 diabetes was demonstrated by an international team of researchers.

Our immune systems have developed various mechanisms to detect, defend against and even destroy micro-organisms that are harmful to the body. This includes antimicrobial peptides and natural proteins that destroy pathogenic bacteria by disrupting their cellular membrane.

Not only are they produced by immune cells, they are also produced by cells whose functions are not immune-related.

A research team coordinated by Julien Diana, of Inserm/CNRS/Université Paris Descartes, is focussing on a category of antimicrobial peptides, i.e. cathelicidins. Apart from their protective function, these peptides have also exhibited immunoregulatory abilities against several autoimmune diseases.

As such, scientists hypothesise that cathelicidins may be involved in the control of type 1 diabetes, an autoimmune disease where certain cells in the immune system attack beta cells in the pancreas which secrete insulin.

Pancreatic Inflammation Protection

Firstly, they observed that beta pancreatic cells in non-diseased mice produce cathelicidins and that, interestingly, this production is impaired in diabetic mice.

To test this hypothesis, they are injecting diabetic mice with cathelicidins where production is defective.

“Injecting cathelicidins inhibits the development of pancreatic inflammation and, as such, suppresses the development of autoimmune disease in these mice” states Julien Diana.

Given that the production of cathelicidins is controlled by short-chain fatty acids produced by gut bacteria, Julien Diana’s team are studying the possibility that this may by the cause of the cathelicidin deficiency associated with diabetes. Indeed, researchers have observed that diabetic mice have a lower level of short-chain fatty acids than that found in healthy mice.

Normal Cathelicidin Levels

By transferring part of the gut bacteria from healthy mice to diabetic mice, they are re-establishing a normal level of cathelicidin. Meanwhile, the transfer of micro-organisms reduces the occurrence of diabetes.

For the authors, “this research is further evidence of the undeniable role microbiota plays in autoimmune diseases, particularly in controlling the development of autoimmune diabetes”.

Preliminary data, as well as scientific literature, suggest that a similar mechanism may exist in humans, paving the way for new therapies against autoimmune diabetes.

Pancreatic beta-cells limit autoimmune diabetes via an immunoregulatory antimicrobial peptide expressed under the influence of the gut microbiota
J. Sun, L. Furio, R. Mecheri, A. M. van der Does, E. Lundeberg, L. Saveanu, Y. Chen, P. van Endert, B. Agerberth and J. Diana
Immunity ; 04 August 2015 DOI: http://dx.doi.org/10.1016/j.immuni.2015.07.013

Photo:EM Unit, UCL Medical School, Royal Free Campus’, Wellcome Images

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