While antimicrobial peptides (AMPs) are more commonly known for their role in defending our body against invading pathogens, recent evidence has suggested that they may perform other immune modulating functions. Indeed, it has been suggested that certain AMPs produced by non-immune cells such as the ones made by the pancreas play an important role in controlling auto-immunity.
New research in mice has now backed up these suggestions – finding that a category of antimicrobial peptides known as cathelicidins (CRAMP) are linked to the risk of developing type 1 diabetes (T1D), and that the short chain fatty acids (SCFAs) produced by our microbiota play a vital role in regulating the production of CRAMP.
“CRAMP administrated to pre-diabetic NOD [non-obese diabetic] mice induced regulatory immune cells in the pancreatic islets, dampening the incidence of autoimmune diabetes,” wrote the international research team – coordinated by Julien Diana at the Necker Institute for Sick Children at INSERM. “Additional investigation revealed that the production of CRAMP by beta-cells was controlled by short-chain fatty acids produced by the gut microbiota.”
In further tests the team found that manipulations to the gut microbiota of non-obese diabetic mice modified the production of CRAMP and levels of inflammation in pancreatic cells, “revealing that the gut microbiota directly shape the pancreatic immune environment and autoimmune diabetes development.”
Diet, the microbiota, and T1D
Diana and his colleagues noted that diet plays a crucial role in the production of short-chain fatty acids in the gut by shaping the composition of the microbiota – adding that dietary fibres are the primary ‘fuel’ for the production of SCFAs.
“Thus, it is tempting to speculate that the rising incidence of T1D and other autoimmune diseases observed in western countries may be associated with nutritional changes that have appeared during the last century,” wrote the team.
“Our study suggests that the simple manipulation of our gut microbiota via the use of specific diet might directly impact on the production of AMPs in peripheral tissues via SCFAs, thus maintaining the local immune homeostasis and prevent the development of autoimmune diseases,” they said.
Diana and colleagues added that preliminary data, as well as the scientific literature, suggest that similar mechanisms may exist in humans, paving the way for new therapies against autoimmune diabetes.
"This research is further evidence of the undeniable role microbiota plays in autoimmune diseases, particularly in controlling the development of autoimmune diabetes,” they suggested.
Published online ahead of print, doi: 10.1016/j.immuni.2015.07.013
“Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota”
Authors: Jia Sun, et al