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Gut Proteins May Indicate Higher Risk of Progression to Type 1 Diabetes

Sep 8, 2018
 

A new study finds that proteins found in the gut can distinguish patients with type 1 diabetes and islet autoimmunity from healthy individuals.

An imbalance of gut bacteria has been the subject of a host of chronic disease states, such as ulcerative colitis, GERD, and many more, but could it also be the key to better understanding type 1 diabetes? Investigators out of The University of Queensland set out to answer this question in a newly published study in Diabetes Care. The study sought to find a link between gut microbiota and the host associated with a risk of type 1 diabetes. The association between pathogenesis of type 1 diabetes and imbalance of gut microbiota is not a new subject, however, as investigators noted. Past studies have indeed found this link, however investigators of this study suggested that this study may be the first of many to tie the functional interaction between type 1 diabetes and gut microbiota.

Four subject groups were examined, including patients with new onset diabetes, seropositive individuals, seronegative individuals, and healthy control subjects. Study investigators used a technique called metaproteomic analysis on fecal proteins to test their hypothesis that “intestinal inflammation is associated with type 1 diabetes progression.” Using metaproteomics, they also sought to determine whether gut microbiota show variation in individuals with islet autoimmunity or clinical disease.

A total of 470 human protein and 10,908 nonhuman protein clusters were observed during the trial.

Among the four groups, no significant differences were noted in the number of human proteins or the ratio of human-to-bacterial proteins. Investigators then sought out to determine whether individuals with diabetes and those who were seropositive could be differentiated from low-risk and healthy individuals. Results of the stool analysis showed that patients with new onset diabetes along with seropositive patients showed a statistically significant difference in their overall microbiota compared with healthy and low-risk individuals.

The study also looked at individual human stool proteins and assessed them for differences between new-onset, seropositive, and control subjects. What investigators found was a measurable difference in the abundance of proteins between the three groups. They observed a markedly reduced output of proteins from the exocrine pancreas in both the patients newly diagnosed as well as the seropositive patients in comparison to the control subjects. This allowed investigators to conclude that not only is exocrine pancreas action decreased in patients with pre-existing diabetes, but also that this reduction in protein output begins before even a diagnosis of diabetes is given.

Investigators also found that proteins associated with intestinal inflammation, such as galectin-3, were increased significantly in patients with new-onset type 1 diabetes.

Investigators of this study claim this may be the largest study to functionally characterize both human and microbial fecal proteins in relation to type 1 diabetes. If indeed true, the results could have a major impact on how gut microbes may be used to identify patients at risk for developing type 1 diabetes.

Practice Pearls:

  • Patients with both new-onset type 1 diabetes and those positive for islet autoimmunity show decreased output of exocrine pancreas proteins compared to healthy individuals.
  • Patients with type 1 diabetes can be distinguished from individuals without diabetes based on an increased number of inflammatory proteins in the gut.
  • Results of the study indicate that seropositive patients should be evaluated for gut microbes that may indicate a higher risk for progression to type 1 diabetes.

Reference:  

Gavin, P. G., Mullaney, J. A., Loo, D., Cao, K. L., Gottlieb, P. A., Hill, M. M., Hamilton-Williams, E. E. (2018). Intestinal Metaproteomics Reveals Host-Microbiota Interactions in Subjects at Risk for Type 1 Diabetes. Diabetes Care, 41(9). doi:10.2337/dc18-0777

Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy