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Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate
BACKGROUND: Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have speci...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404562/ https://www.ncbi.nlm.nih.gov/pubmed/36002880 http://dx.doi.org/10.1186/s40168-022-01306-y |
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author | Huber-Ruano, Isabel Calvo, Enrique Mayneris-Perxachs, Jordi Rodríguez-Peña, M-Mar Ceperuelo-Mallafré, Victòria Cedó, Lídia Núñez-Roa, Catalina Miro-Blanch, Joan Arnoriaga-Rodríguez, María Balvay, Aurélie Maudet, Claire García-Roves, Pablo Yanes, Oscar Rabot, Sylvie Grimaud, Ghjuvan Micaelu De Prisco, Annachiara Amoruso, Angela Fernández-Real, José Manuel Vendrell, Joan Fernández-Veledo, Sonia |
author_facet | Huber-Ruano, Isabel Calvo, Enrique Mayneris-Perxachs, Jordi Rodríguez-Peña, M-Mar Ceperuelo-Mallafré, Victòria Cedó, Lídia Núñez-Roa, Catalina Miro-Blanch, Joan Arnoriaga-Rodríguez, María Balvay, Aurélie Maudet, Claire García-Roves, Pablo Yanes, Oscar Rabot, Sylvie Grimaud, Ghjuvan Micaelu De Prisco, Annachiara Amoruso, Angela Fernández-Real, José Manuel Vendrell, Joan Fernández-Veledo, Sonia |
author_sort | Huber-Ruano, Isabel |
collection | PubMed |
description | BACKGROUND: Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting. RESULTS: Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity. We also show in vivo that therapeutic treatments with selected bacteria diminish the levels of circulating succinate in obese mice. Specifically, we demonstrate that Odoribacter laneus is a promising probiotic based on its ability to deplete succinate and improve glucose tolerance and the inflammatory profile in two independent models of obesity (db/db mice and diet-induced obese mice). Mechanistically, this is partly mediated by the succinate receptor 1. Supporting these preclinical findings, we demonstrate an inverse correlation between plasma and fecal levels of succinate in a cohort of patients with severe obesity. We also show that plasma succinate, which is associated with several components of metabolic syndrome including waist circumference, triglycerides, and uric acid, among others, is a primary determinant of insulin sensitivity evaluated by the euglycemic-hyperinsulinemic clamp. CONCLUSIONS: Overall, our work uncovers O. laneus as a promising next-generation probiotic to deplete succinate and improve glucose tolerance and obesity-related inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01306-y. |
format | Online Article Text |
id | pubmed-9404562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94045622022-08-26 Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate Huber-Ruano, Isabel Calvo, Enrique Mayneris-Perxachs, Jordi Rodríguez-Peña, M-Mar Ceperuelo-Mallafré, Victòria Cedó, Lídia Núñez-Roa, Catalina Miro-Blanch, Joan Arnoriaga-Rodríguez, María Balvay, Aurélie Maudet, Claire García-Roves, Pablo Yanes, Oscar Rabot, Sylvie Grimaud, Ghjuvan Micaelu De Prisco, Annachiara Amoruso, Angela Fernández-Real, José Manuel Vendrell, Joan Fernández-Veledo, Sonia Microbiome Research BACKGROUND: Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting. RESULTS: Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity. We also show in vivo that therapeutic treatments with selected bacteria diminish the levels of circulating succinate in obese mice. Specifically, we demonstrate that Odoribacter laneus is a promising probiotic based on its ability to deplete succinate and improve glucose tolerance and the inflammatory profile in two independent models of obesity (db/db mice and diet-induced obese mice). Mechanistically, this is partly mediated by the succinate receptor 1. Supporting these preclinical findings, we demonstrate an inverse correlation between plasma and fecal levels of succinate in a cohort of patients with severe obesity. We also show that plasma succinate, which is associated with several components of metabolic syndrome including waist circumference, triglycerides, and uric acid, among others, is a primary determinant of insulin sensitivity evaluated by the euglycemic-hyperinsulinemic clamp. CONCLUSIONS: Overall, our work uncovers O. laneus as a promising next-generation probiotic to deplete succinate and improve glucose tolerance and obesity-related inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01306-y. BioMed Central 2022-08-25 /pmc/articles/PMC9404562/ /pubmed/36002880 http://dx.doi.org/10.1186/s40168-022-01306-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Huber-Ruano, Isabel Calvo, Enrique Mayneris-Perxachs, Jordi Rodríguez-Peña, M-Mar Ceperuelo-Mallafré, Victòria Cedó, Lídia Núñez-Roa, Catalina Miro-Blanch, Joan Arnoriaga-Rodríguez, María Balvay, Aurélie Maudet, Claire García-Roves, Pablo Yanes, Oscar Rabot, Sylvie Grimaud, Ghjuvan Micaelu De Prisco, Annachiara Amoruso, Angela Fernández-Real, José Manuel Vendrell, Joan Fernández-Veledo, Sonia Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
title | Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
title_full | Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
title_fullStr | Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
title_full_unstemmed | Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
title_short | Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
title_sort | orally administered odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404562/ https://www.ncbi.nlm.nih.gov/pubmed/36002880 http://dx.doi.org/10.1186/s40168-022-01306-y |
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