Title
Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study
Document Type
Article
Journal Title
Frontiers in Immunology
Publication Date
2019
Volume
10
Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic β-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes metabolic abnormalities and inflammation. We have tested this hypothesis by exposing human islets to BD and RG in vitro, after which RNA-Seq analysis was performed. The bacteria altered expression of many islet genes. The commonly upregulated genes by these bacteria were cytokines, chemokines and enzymes, suggesting a significant effect of gut bacteria on islet antimicrobial and biosynthetic pathways. Additionally, each bacteria displayed a unique set of differentially expressed genes (DEGs). Ingenuity pathway analysis of DEGs revealed that top activated pathways and diseases included TREM1 signaling and inflammatory response, illustrating the ability of bacteria to induce islet inflammation. The increased levels of selected factors were confirmed using immunoblotting and ELISA methods. Our data demonstrate that islets produce a complex anti-bacterial response. The response includes both symbiotic and pathogenic aspects. Both oxidative damage and leukocyte recruitment factors were prominent, which could induce beta cell damage and subsequent autoimmunity.
ISSN
1664-3224
DOI Link
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Abdellatif, Ahmed M.; Jensen Smith, Heather; Harms, Robert Z.; and Sarvetnick, Nora, "Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study" (2019). Journal Articles: Regenerative Medicine. 28.
https://digitalcommons.unmc.edu/reg_articles/28
Table_2_Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria_ A Transcriptome-Based Study.DOCX (16 kB)
Table_3_Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria_ A Transcriptome-Based Study.xlsx (420 kB)
Table_4_Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria_ A Transcriptome-Based Study.xls (39 kB)
Table_5_Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria_ A Transcriptome-Based Study.xlsx (60 kB)
Table_6_Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria_ A Transcriptome-Based Study.xlsx (28 kB)