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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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.
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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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