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

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 5; pp. 1468 - 1477
• Main Authors: Pellegrini, Silvia, Sordi, Valeria, Bolla, Andrea Mario, Saita, Diego, Ferrarese, Roberto, Canducci, Filippo, Clementi, Massimo, Invernizzi, Francesca, Mariani, Alberto, Bonfanti, Riccardo, Barera, Graziano, Testoni, Pier Alberto, Doglioni, Claudio, Bosi, Emanuele, Piemonti, Lorenzo
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2017
• Subjects: Adolescent; Adult; Aged; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - immunology; Bacteroidetes; Biopsy; C-Reactive Protein - genetics; C-Reactive Protein - immunology; Case-Control Studies; CCL19 protein; CCL22 protein; CCR2 protein; Celiac disease; Celiac Disease - immunology; Celiac Disease - microbiology; Chemokine CCL19 - genetics; Chemokine CCL19 - immunology; Chemokine CCL22 - genetics; Chemokine CCL22 - immunology; Child; Child, Preschool; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - immunology; Cyclooxygenase-2; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - microbiology; Digestive system; Duodenum; Duodenum - immunology; Duodenum - microbiology; Female; Firmicutes; Gastrointestinal Microbiome - genetics; Gastrointestinal tract; Gene expression; Humans; Immunohistochemistry; Infant; Inflammation; Inflammatory diseases; Interleukin 4 receptors; Interleukin-4 Receptor alpha Subunit - genetics; Interleukin-4 Receptor alpha Subunit - immunology; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestine; Macrophages; Male; Microbiomes; Microbiota; Middle Aged; Monocyte chemoattractant protein 1; Monocyte Chemoattractant Proteins - genetics; Monocyte Chemoattractant Proteins - immunology; Monocytes; Mucosa; Real-Time Polymerase Chain Reaction; Receptors, CCR2 - genetics; Receptors, CCR2 - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Ribosomal, 16S - genetics; rRNA 16S; Serum Amyloid P-Component - genetics; Serum Amyloid P-Component - immunology; Small intestine; Transcriptome; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - immunology; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2016-3222

Increasing evidences suggest a correlation between gut and type 1 diabetes (T1D). 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. 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. Inflammation was evaluated by gene expression study and immunohistochemistry. Microbiome composition was analyzed by 16S ribosomal RNA gene sequencing. 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. 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.