The Journal of clinical endocrinology and metabolism · 2017
Duodenal Mucosa of Patients With Type 1 Diabetes Shows Distinctive Inflammatory Profile and Microbiota.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAdultAgedAntigens, CDAntigens, Differentiation, MyelomonocyticC-Reactive ProteinCase-Control StudiesCeliac DiseaseChemokine CCL19Chemokine CCL22ChildChild, PreschoolCyclooxygenase 2Diabetes Mellitus, Type 1DuodenumFemaleGastrointestinal MicrobiomeHumansInfantInterleukin-4 Receptor alpha SubunitIntestinal MucosaMaleMiddle AgedMonocyte Chemoattractant ProteinsRNA, Ribosomal, 16SReal-Time Polymerase Chain ReactionReceptors, CCR2Reverse Transcriptase Polymerase Chain ReactionSerum Amyloid P-ComponentTranscriptomeTumor Necrosis Factor-alphaVascular Endothelial Growth Factor AYoung AdultPentraxinsCD68 Molecule