Duodenal Mucosa of Patients With Type 1 Diabetes Shows Distinctive Inflammatory Profile and Microbiota

Silvia Pellegrini, Valeria Sordi, Andrea Mario Bolla, Diego Saita, Roberto Ferrarese, Filippo Canducci, Massimo Clementi, Francesca Invernizzi, Alberto Mariani, Riccardo Bonfanti, Graziano Barera, Pier Alberto Testoni, Claudio Doglioni, Emanuele Bosi, Lorenzo Piemonti

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


Context: Increasing evidences suggest a correlation between gut and type 1 diabetes (T1D).

Objective: The objective of this study is to evaluate the gut inflammatory profile and microbiota in patients with T1D compared with healthy control (CTRL) subjects and patients with celiac disease (CD) as gut inflammatory disease controls.

Design/Setting/Participants: The inflammatory status and microbiome composition were evaluated in biopsies of the duodenal mucosa of patients with T1D (n = 19), in patients with CD (n = 19), and CTRL subjects (n = 16) recruited at San Raffaele Scientific Institute, in Milan, Italy, between 2009 and 2015.

Main Outcome Measures: Inflammation was evaluated by gene expression study and immunohistochemistry. Microbiome composition was analyzed by 16S ribosomal RNA gene sequencing.

Results: An increased expression of CCL13, CCL19, CCL22, CCR2, COX2, IL4R, CD68, PTX3, TNFα, and VEGFA was observed in patients with T1D compared with CTRL subjects and patients with CD. Immunohistochemical analysis confirmed T1D-specific inflammatory status compared with healthy and CD control tissues, mainly characterized by the increase of the monocyte/macrophage lineage infiltration. The T1D duodenal mucosal microbiome results were different from the other groups, with an increase in Firmicutes and Firmicutes/Bacteroidetes ratio and a reduction in Proteobacteria and Bacteroidetes. The expression of genes specific for T1D inflammation was associated with the abundance of specific bacteria in the duodenum.

Conclusions: This study shows that duodenal mucosa in T1D presents disease-specific abnormalities in the inflammatory profile and microbiota. Understanding the mechanisms underlying these features is critical to disentangle the complex pathogenesis of T1D and to gain new perspectives for future therapies targeting the intestine.

Original languageEnglish
Pages (from-to)1468-1477
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
Publication statusPublished - 2017


  • Adolescent
  • Adult
  • Aged
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • C-Reactive Protein
  • Case-Control Studies
  • Celiac Disease
  • Chemokine CCL19
  • Chemokine CCL22
  • Child
  • Child, Preschool
  • Cyclooxygenase 2
  • Diabetes Mellitus, Type 1
  • Duodenum
  • Female
  • Gastrointestinal Microbiome
  • Humans
  • Infant
  • Interleukin-4 Receptor alpha Subunit
  • Intestinal Mucosa
  • Male
  • Middle Aged
  • Monocyte Chemoattractant Proteins
  • RNA, Ribosomal, 16S
  • Real-Time Polymerase Chain Reaction
  • Receptors, CCR2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Amyloid P-Component
  • Transcriptome
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Young Adult
  • Journal Article


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