Duodenal mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and microbiota

Silvia Pellegrini, V Sordi, AM Bolla, D Saita, R Ferrarese, F Canducci, M Clementi, F Invernizzi, A. Mariani, R Bonfanti, G Barera, PA Testoni, C Doglioni, E Bosi, L Piemonti

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 compositionwere 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, TNFa, and VEGFA was observed in patientswith T1D compared with CTRL subjects and patientswith 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. (J Clin Endocrinol Metab 102: 1468-1477, 2017). © 2017 Endocrine Society.
Original languageEnglish
Pages (from-to)1468-1477
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume102
Issue number5
DOIs
Publication statusPublished - 2017

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Microbiota
Medical problems
Type 1 Diabetes Mellitus
Mucous Membrane
Celiac Disease
Bacteroidetes
Disease control
Genes
16S Ribosomal RNA
Inflammation
RNA Sequence Analysis
Gene Expression
Proteobacteria
Biopsy
Macrophages
rRNA Genes
Duodenum
Infiltration
Gene expression
Italy

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Duodenal mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and microbiota. / Pellegrini, Silvia; Sordi, V; Bolla, AM; Saita, D; Ferrarese, R; Canducci, F; Clementi, M; Invernizzi, F; Mariani, A.; Bonfanti, R; Barera, G; Testoni, PA; Doglioni, C; Bosi, E; Piemonti, L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 5, 2017, p. 1468-1477.

Research output: Contribution to journalArticle

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abstract = "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 compositionwere 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, TNFa, and VEGFA was observed in patientswith T1D compared with CTRL subjects and patientswith 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. (J Clin Endocrinol Metab 102: 1468-1477, 2017). {\circledC} 2017 Endocrine Society.",
author = "Silvia Pellegrini and V Sordi and AM Bolla and D Saita and R Ferrarese and F Canducci and M Clementi and F Invernizzi and A. Mariani and R Bonfanti and G Barera and PA Testoni and C Doglioni and E Bosi and L Piemonti",
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T1 - Duodenal mucosa of patients with type 1 diabetes shows distinctive inflammatory profile and microbiota

AU - Pellegrini, Silvia

AU - Sordi, V

AU - Bolla, AM

AU - Saita, D

AU - Ferrarese, R

AU - Canducci, F

AU - Clementi, M

AU - Invernizzi, F

AU - Mariani, A.

AU - Bonfanti, R

AU - Barera, G

AU - Testoni, PA

AU - Doglioni, C

AU - Bosi, E

AU - Piemonti, L

PY - 2017

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N2 - 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 compositionwere 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, TNFa, and VEGFA was observed in patientswith T1D compared with CTRL subjects and patientswith 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. (J Clin Endocrinol Metab 102: 1468-1477, 2017). © 2017 Endocrine Society.

AB - 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 compositionwere 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, TNFa, and VEGFA was observed in patientswith T1D compared with CTRL subjects and patientswith 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. (J Clin Endocrinol Metab 102: 1468-1477, 2017). © 2017 Endocrine Society.

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DO - 10.1210/jc.2016-3222

M3 - Article

VL - 102

SP - 1468

EP - 1477

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

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ER -