Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia
| Autor: | Frédéric Lopez, Céline Pomié, Anthony Puel, Vincent Blasco-Baque, Lucile Garidou, Philippe Valet, Michael Courtney, Rémy Burcelin, Aurélie Waget, Jacques Amar, Vincent Azalbert, Benjamin Lelouvier, Florence Servant, Pascale Klopp, Simon Nicolas, Cédric Dray, Pascale Loubieres |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine LN Lymph nodes endocrine system diseases T2D Type 2 diabetes Adipose tissue chemical and pharmacologic phenomena 030209 endocrinology & metabolism Type 2 diabetes Biology Gut flora digestive system 03 medical and health sciences 0302 clinical medicine Insulin resistance APC Antigen presenting cells Immunity medicine lcsh:RC31-1245 Antigen-presenting cell Molecular Biology digestive oral and skin physiology nutritional and metabolic diseases Cell Biology biochemical phenomena metabolism and nutrition medicine.disease biology.organism_classification Acquired immune system Gut microbiota and metabolic diseases AT Adipose tissue Crosstalk (biology) 030104 developmental biology VL Vastus lateralis muscle Immunology bacteria Original Article NC Normal chow |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 5, Iss 6, Pp 392-403 (2016) |
| ISSN: | 2212-8778 |
| Popis: | Objective To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. Methods We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Results Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Conclusions Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet. Highlights • Triggering adaptive immune response with ileum bacteria extracts prevents HFD-induced metabolic disease. • Triggering adaptive immune response with ileum bacteria extracts improves gut microbiota dysbiosis. • Triggering adaptive immune response with ileum bacteria extract regulates the intestinal immune system. • First microbiota based vaccination strategy of metabolic disease. |
| Databáze: | OpenAIRE |
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