Gut microbiota shown to predict type 1 diabetes progression

Researchers used metaproteomics to study host-microbiota interaction in the diabetic gut, and identified a unique signature in the stool of individuals with type 1 diabetes (T1D) that may be beneficial in monitoring disease progression or response to therapy, according to a new study published in Diabetes Care.

Gut microbiota is influenced by genetics and environmental factors, such as diet and hygiene. Dysbiosis of the gut microbiota has been tied to various autoimmune diseases, including T1D. Researchers have yet to determine how gut microbiota interfere with the intestinal environment and immunity in T1D, and no clear consensus exists as to what comprises type 1 diabetes-associated microbiota.

“While there has been a suspected link between gut bacteria and [T1D] disease progression, a direct relationship between pancreas function and gut bacteria hasn’t been shown until now. By studying the stool samples of participants, we found that changes in gut bacteria weren’t just a side effect of the disease, but are likely related to disease progression,” said corresponding author Emma Hamilton-Williams, PhD, senior research fellow, University of Queensland Diamantina Institute, Brisbane, QLD, Australia.

“Seeing the same characteristics in recently diagnosed patients and undiagnosed high-risk relatives means these proteins may be used to predict a future diabetes diagnosis,” she added.

In this study, the researchers performed metaproteomic analysis on stool samples from 101 individuals who either had new-onset T1D, high- or low-risk first-degree relatives, or were designated as healthy control participants. Individuals with gastrointestinal disease, known infections, or who were treated with antibiotics in the 4 weeks preceding the study were excluded from enrollment.

The team included proteins found in >40% of any study group in univariate and multivariate analysis, and these proteins were considered for functional pathway assignments.

“We used metaproteomics of fecal proteins to test the hypothesis that intestinal inflammation is associated with type 1 diabetes progression and to determine whether the functional characteristics of the microbiota are altered in individuals with islet autoimmunity or clinical disease,” the authors wrote.

The team highlighted four main results of their study.

1. Human and microbial proteins found in stool likely distinguish individuals with continuing islet autoimmunity from low-risk and healthy individuals.
2. Participants who were positive for new-onset and islet antibodies exhibit decreased markers of exocrine pancreas output compared with control participants.
3. Individuals with new-onset T1D had a greater presence of inflammatory proteins in their stool.
4. Findings demonstrated a functional relationship between proteins and reduced bacterial taxa among new-onset and seropositive individuals with mucosal barrier function and exocrine pancreas output.

Results of this study also identified a negative interrelationship between the presence of specific stool antibodies and taxa associated with intestinal health, and indicated a link between the plethora of exocrine pancreatic proteins and anti-inflammatory taxa and mucosal barrier function.

The researchers noted that, although they observed a marked diabetes-associated signature in this study sample, these differences in protein abundance need to be confirmed by a larger, independent cohort study. The team also acknowledged that because they did not measure c-peptide, they were unable to identify any potential connections between beta cell function and stool proteins. Moreover, the shotgun proteomic approach taken by the researchers lacked sensitivity and reproducibility; therefore, these findings warrant further validation via other methods.

“These data support that type 1 diabetes patients have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset type 1 diabetes patients and show for the first time that this dysfunction is present in high-risk individuals prior to disease onset,” concluded the authors.