A new study from Lingköping University in Sweden and the University of Florida has revealed that the gut microbiome of children with a high genetic risk of developing type 1 diabetes is markedly different from children who have a low risk of developing the condition.
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The new study suggests that an individual’s response to environmental factors that contribute to the development type 1 diabetes is influenced by genetic factors, and claims it is the first to report significant associations between genetic risk and changes in the gut microbiome.
Type 1 diabetes is an autoimmune condition in which the levels of blood glucose become too high due to a lack of insulin produced by the body.
The condition affects 422 million people worldwide, according to statistics released by the World Health Organization, and is a major cause of blindness, renal failure, stroke, and lower-limb amputations.
Both type 1 and type 2 diabetes have been extensively studied because of their severe effects, but the particular cohort used in this new study is “uniquely valuable”, as described by Johnny Ludvigsson, senior professor in the Department of Clinical and Experimental Medicine, Linköping University, and senior consultant at HRH Crown Princess Victoria Children’s Hospital, Linköping University Hospital.
The All Babies in Southeast Sweden (ABIS) cohort used in this new study aims to find out why children develop autoimmune diseases, in particular type 1 diabetes.
The cohort included 17,055 children born between 1997 and 1999, who have been monitored since birth with questionnaires covering information on duration of breastfeeding, antibiotic use, and diet, and biological samples (blood, urine, hair, and stool). The children were monitored at ages 1, 3, 5 and 8, and older.
Bacterial diversity was significantly different in children with a high risk of diabetes
This new study, published in Nature Communications, included 403 children whose genetic risk was analyzed by studying the connections between genetic predisposition and their gut flora, with a focus on variants in the human leukocyte antigen (HLA) genes:
“Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations. These genes remain by fair the greatest risk factors in the development of type 1 diabetes and celiac disease. Despite this, little is known about HLA influences on the composition of the human gut microbiome, a potential source of environmental influence on the disease.”
“Certain bacterial species were not found at all in children with high genetic risk, but were found in those with low or no risk,” Ludvigsson said. “This is very interesting, as this could mean that certain species have protective effects and may be useful in future treatment to prevent autoimmune diseases.
“It may be that certain species cannot survive in individuals with high genetic risk.”
The study suggests that two members of the family of bacteria Peptostreptococcaceae, Intestinibacter and Romboutsia, are “consistently associated with lower genetic risk HLA genotypes”, which may hint at how to prevent type 1 diabetes by reducing the functions of these gut bacteria in high risk genotypes.
It also suggests that probiotics have “great potential” to facilitate changes in the microbiome to prevent or improve type 1 diabetes, among other autoimmune diseases.
A separate study found that impaired function of the intestinal epithelial barrier possibly connected to the make-up of gut microbiota was found in people with type 1 diabetes.
The authors suggested that these factors were could be responsible for poor glycemic control. They investigated the effect of prebiotics on children with type 1 diabetes, and concluded
“Prebiotic supplementation, specially oligofructose-enriched insulin, is a potentially novel, inexpensive, low-risk treatment addition for T1D that may improve glycemic control,” furthering the evidence that pre- and pro-biotics could play an important role in preventing type 1 diabetes.
Future research is needed to gain a deeper understanding of the effects of genetics and gut flora on type 1 diabetes incidence, which may in turn benefit the understanding and treatment of other autoimmune diseases such as celiac disease and rheumatoid arthritis.
Russel, J. T., et al. (2019). Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome. Nature Communications. https://www.nature.com/articles/s41467-019-11460-x