The intestinal microbiota in people with type 1 and those with MODY2 differs in abundance and type compared to people without.
Type 1 diabetes is an immune-mediated disease that leads to the destruction of beta cells in the pancreas. It is widely acknowledged that type 1 diabetes has a genetic factor to its development, but there are environmental factors that have been linked to its development as well. For example, diet in early life and use of antibiotics showed association to type 1 development in some studies. These environmental factors play a role in gut microbiota. Some animal studies have linked the microbiome to type 1 diabetes. Also, intestinal microbes help maintain and regulate intestinal permeability. People with type 1 diabetes have increased intestinal permeability, which may be from reduced microbes in the intestines.
Maturity-onset diabetes (MODY) is rare form of diabetes that is genetic. MODY2 is the most common form of MODY and is caused by heterozygous inactivating mutation in the glucokinase gene. It is not usually linked with obesity and is not caused by autoimmunity. This population of children was researched in a new study that compared the fecal microbiota of MODY2 persons and those with type 1 diabetes. The study hypothesized if the microbiota was different in a person with type 1 compared to someone with MODY2, the intestinal flora could play a role in the autoimmune process of the person with type 1. The aim of the study was to determine similarities and differences in gut microbiota, functional capacity, low-grade inflammation, and gut permeability among children with type 1 diabetes, MODY2, and healthy subjects.
The study included 15 children with type 1 diabetes, 15 children with MODY2, and 13 children without either. Fecal samples were collected and microbiota was sequenced. The Chao index was used to test for community richness and Shannon index for microbiota diversity. Results found the Chao index was similar in all participants. The Shannon index was significantly different in children without either condition versus children with diabetes. It showed type 1 and MODY2 had lower microbiota diversity. All participants had phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Of those microbes, 64.69% were Bacteroidetes in people who have type 1 compared to 39.85% MODY2 and 49.85% subjects without either condition. Of the Bacteroidetes, the Bacteroidaceae family made up 71.48% of the sample in type 1 diabetes compared to 55.43% MODY2 and 59.62% healthy samples. Rikenellaceae family was also more abundant in the type 1 diabetes samples. Only 19.6% of diversity was Firmicutes in type 1 diabetes samples and 31.5% MODY2 and 29.69% in healthy samples.
Type 1 diabetes samples also showed significant increase in abundance of Ruminococcus, Veillonella, Blautia, Enterobacter, and Streptococcus genera. They had a decrease in abundance of Bifidobacterium, Roseburia, Faecalibacterium, and Lachnospira compared to MODY2 and healthy samples. Lastly, zolulin, a regulator of intestinal permeability, was found in MODY2 and type 1 diabetes samples, which indicate increased gut permeability.
This study was the first of its kind. It found an association between bacterial flora and type 1 diabetes and MODY2. There were significant differences in type and abundance of microbes. This data could lead to further research to help identify if a patient is at risk of developing type 1 diabetes based on their micro flora and could also help discover ways to slow the progression of the disease.
- Gut flora was different in types and abundance among people with type 1 or MODY2, and children without.
- Patients with type 1 and MODY2 had more gut permeability, which may be due to impaired epithelial integrity.
- Future studies could help lead to earlier detection of type 1 diabetes and possibly ways to slow the autoimmune process.
Isabel Leiva-Gea, Lidia Sánchez-Alcoholado, Beatriz Martín-Tejedor, Daniel Castellano-Castillo, Isabel Moreno-Indias, Antonio Urda-Cardona, Francisco J. Tinahones, José Carlos Fernández-García, María Isabel Queipo-Ortuño. Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study. Diabetes Care (Nov 2018), 41 (11) 2385-2395; DOI: 10.2337/dc18-0253
Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy