What is already known
Type 1 diabetes is an autoimmune disease in which the pancreas produces little or no insulin — the hormone that controls glucose levels in the blood. Studies in animal models have suggested that diet can influence the condition — perhaps through the microbiota. However, whether dietary interventions are mediated by gut microbes remains unclear.
What this research adds
Working in mice, researchers found that a diet based on casein, a protein that is commonly found in milk, protects diabetic animals by improving the function of insulin-producing cells. However, gluten — a protein found in certain cereal grains — as well as microbes such as Enterococcus faecalis, which produce specific enzymes that can break down gluten, were able to reverse casein-mediated protection. Breaking down gluten activated the immune system and increased inflammation in the pancreas.
Conclusions
The findings may inform dietary interventions to help protect people against type 1 diabetes and other autoimmune diseases.
Type 1 diabetes is an autoimmune disease in which the pancreas produces little or no insulin — the hormone that controls glucose levels in the blood. Now, researchers have found that some components of the gut microbiota can reverse the beneficial effects of dietary interventions that protect mice against type 1 diabetes.
The findings, published in Cell Host & Microbe, may inform strategies to help protect people against type 1 diabetes and other autoimmune diseases.
Previous studies in animal models have suggested that diet can influence the type 1 diabetes — perhaps through the microbiota. However, whether dietary interventions are mediated by gut microbes remains unclear.
To address this question, Alexander Chervonsky at the University of Chicago and his colleagues study diet-microbiota interactions in a mouse model of type 1 diabetes.
Diabetes protection
The researchers fed mice a diet containing hydrolyzed casein, a protein that is commonly found in milk, as the only source of amino acids. This diet has been previously reported to protect diabetes-prone mice and rats from the condition.
The team found that hydrolyzed casein protected mice from type 1 diabetes also in the absence of the microbiota. Diabetes-prone mice on the hydrolyzed casein diet responded to glucose slower than mice on a standard diet. Hydrolyzed casein appeared to boost insulin secretion by reducing the stress of beta cells, a type of cells that make insulin and that are typically found in the pancreas in clusters known as islets.
“We suggest that the potential mechanism of protection by [hydrolyzed casein] diet is the reduction of intrinsic damage to the islets caused by cellular stress resulting in a reduction in the overall damage caused by autoimmunity and the prevention or postponement of hyperglycemia,” the researchers say.
Reversing benefits
When the researchers added gluten — a protein found in certain cereal grains — to the hydrolyzed casein diet, mice with an intact microbiota were no longer protected from diabetes, but germ-free mice were.
Further experiments revealed that microbes such as Enterococcus faecalis, which produce specific enzymes that can break down gluten, were able to reverse casein-mediated protection from diabetes. Breaking down gluten activated the mice’s immune system and increased inflammation in the pancreas, the researchers found.
The results suggest that dietary components such as gluten require processing by the members of the microbiota to trigger autoimmune reactions. “Whether other proteins can utilize similar mechanisms (overcoming positive effects of milk proteins or on their own) is very important,” the researchers say. “We expect our findings to lead to new approaches to protection from autoimmunity and inflammation.”
