Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment

The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D) via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. I...

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Published in:Journal of Diabetes Research Vol. 2016; no. 2016; pp. 1 - 12
Main Authors: Falcone, Marika, Canducci, Filippo, Saita, Diego, Ferrarese, Roberto, Cosorich, Ilaria, Di Pietro, Caterina, Sorini, Chiara, Dolpady, Jayashree, Clementi, Massimo
Format: Journal Article
Language:English
Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016
John Wiley & Sons, Inc
Wiley
Subjects:
Administration, Oral
Age Factors
Animals
Autoimmunity
Cellular Microenvironment
Cytokines
Diabetes
Diabetes Mellitus, Type 1 - enzymology
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - microbiology
Diabetes Mellitus, Type 1 - prevention & control
Disease Models, Animal
Flow cytometry
Gastrointestinal Microbiome
Homeostasis
Hypotheses
Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Inflammasomes - immunology
Inflammasomes - metabolism
Interleukin-1beta - metabolism
Interleukin-33 - metabolism
Intestines - enzymology
Intestines - immunology
Intestines - microbiology
Lactobacillaceae - growth & development
Lactobacillaceae - immunology
Lymphatic system
Mice, Inbred NOD
Microbiota
Microbiota (Symbiotic organisms)
Pathogenesis
Probiotics
Probiotics - administration & dosage
Software
Th1 Cells - immunology
Th1 Cells - metabolism
Th1 Cells - microbiology
Th17 Cells - immunology
Th17 Cells - metabolism
Th17 Cells - microbiology
Tretinoin - pharmacology
Type 1 diabetes
Vitamin A
St Louis Missouri
United States > US
ISSN:2314-6745, 2314-6753, 2314-6753
Online Access:Get full text
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Summary:The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D) via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA), protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO) and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103+ DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN) of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.
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Academic Editor: Abdelaziz Amrani
ISSN:2314-6745
2314-6753
2314-6753
DOI:10.1155/2016/7569431