Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study

Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora E. Sarvetnick

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2623
JournalFrontiers in immunology
Volume10
DOIs
StatePublished - Nov 8 2019

Fingerprint

Type 1 Diabetes Mellitus
Transcriptome
Bacteria
Ruminococcus
Bacteroides
Autoimmunity
Genes
Inflammation
Biosynthetic Pathways
Chemokines
Immunoblotting
Autoimmune Diseases
Leukocytes
Homeostasis
Chronic Disease
Enzyme-Linked Immunosorbent Assay
RNA
Cytokines
Enzymes

Keywords

  • Bacteroides dorei
  • Ruminococcus gnavus
  • autoimmunity
  • dysbiosis
  • type 1 diabetes
  • β-cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria : A Transcriptome-Based Study. / Abdellatif, Ahmed M.; Jensen Smith, Heather; Harms, Robert Z.; Sarvetnick, Nora E.

In: Frontiers in immunology, Vol. 10, 2623, 08.11.2019.

Research output: Contribution to journalArticle

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