Monday, 17 June, 2024
HomeEndocrinologyLink between Type 1 diabetes and inflammation of the digestive tract

Link between Type 1 diabetes and inflammation of the digestive tract

People with Type 1 diabetes exhibit inflammation in the digestive tract and gut bacteria – a pattern that differs from individuals who do not have diabetes or those who have celiac disease, according to an Italian study.

Type 1 diabetes occurs when the body produces little to no insulin. The hormone plays a crucial role in carrying blood sugar to the body's cells. Type 1 diabetes tends to begin affecting people at a young age. It typically develops when the body's own immune system attacks the pancreas and prevents the gland from producing insulin. As a result, Type 1 diabetes is an autoimmune condition.

"Our findings indicate the individuals with Type 1 diabetes have an inflammatory signature and microbiome that differ from what we see in people who do not have diabetes or even in those with other autoimmune conditions such as celiac disease," said the study's senior author, Dr Lorenzo Piemonti of the Diabetes Research Institute at San Raffaele Hospital in Milan, Italy. "Some researchers have theorized that the gut may contribute to the development of Type 1 diabetes, so it is important to understand how the disease affects the digestive system and microbiome."

The study examined the microbiome of 54 individuals who underwent endoscopies and biopsies of the first part of the small intestine, known as the duodenum, at San Raffaele Hospital between 2009 and 2015. The individuals were either undergoing a diagnostic procedure to diagnose a gastrointestinal disorder or volunteered to participate in the study.

This approach allowed researchers to directly assess the gastrointestinal tract and bacteria, unlike studies that rely on stool samples for analysis. The analysis of tissues sampled from the endoscopy produced high-resolution snapshots of the innermost layer of the gastrointestinal tract.

Individuals with Type 1 diabetes showed significantly more signs of inflammation of the gut's mucous membrane linked to 10 specific genes than the participants who had celiac disease and control healthy subjects. Participants with Type 1 diabetes also displayed a distinct combination of gut bacteria that was different from the other two groups.

"We don't know if Type 1 diabetes' signature effect on the gut is caused by or the result of the body's own attacks on the pancreas," Piemonti said. "By exploring this, we may be able to find new ways to treat the disease by targeting the unique gastrointestinal characteristics of individuals with Type 1 diabetes."

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 to healthy controls (CTRL) 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), CD (n=19) and CTRL (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 rRNA gene sequencing.
Results: An increased expression of CCL13, CCL19, CCL22, CCR2, COX2, IL4R, CD68, PTX3, TNFα and VEGFA genes was observed in T1D patients compared to CTRL and CD. The immunohistochemical analysis confirmed T1D specific inflammatory status compared to healthy and CD control tissues, mainly characterized by the increase of the monocyte/macrophage lineage infiltration. Also the T1D duodenal mucosal microbiome resulted 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 duodenum.
Conclusions: This study shows that duodenal mucosa in T1D presents disease specific abnormalities in inflammatory profile and microbiota. Understanding the mechanisms underlying these features is critical to disentangle the complex pathogenesis of T1D and indicate new perspectives for future therapies targeting the intestine.

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

[link url=""]Endocrine Society material[/link]
[link url=""]Journal of Clinical Endocrinology & Metabolism abstract[/link]

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