Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate
(2022) In Microbiome 10(1).- Abstract
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... (More)
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. [MediaObject not available: see fulltext.].
(Less)
- 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
LU
; De Prisco, Annachiara
; Amoruso, Angela
; Fernández-Real, José Manuel
; Vendrell, Joan
and Fernández-Veledo, Sonia
(Less) - publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- keywords
- Animal models, Glucose tolerance, Inflammation, Obesity, Probiotics, Succinate
- in
- Microbiome
- volume
- 10
- issue
- 1
- article number
- 135
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85136508140
- pmid:36002880
- ISSN
- 2049-2618
- DOI
- 10.1186/s40168-022-01306-y
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2022, The Author(s).
- id
- 19165345-75dc-466f-a0d3-ee71b22d9ed8
- date added to LUP
- 2024-11-25 16:10:46
- date last changed
- 2025-06-11 10:47:24
@article{19165345-75dc-466f-a0d3-ee71b22d9ed8,
abstract = {{<p>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. [MediaObject not available: see fulltext.].</p>}},
author = {{Huber-Ruano, Isabel and Calvo, Enrique and Mayneris-Perxachs, Jordi and Rodríguez-Peña, M. Mar and Ceperuelo-Mallafré, Victòria and Cedó, Lídia and Núñez-Roa, Catalina and Miro-Blanch, Joan and Arnoriaga-Rodríguez, María and Balvay, Aurélie and Maudet, Claire and García-Roves, Pablo and Yanes, Oscar and Rabot, Sylvie and Grimaud, Ghjuvan Micaelu and De Prisco, Annachiara and Amoruso, Angela and Fernández-Real, José Manuel and Vendrell, Joan and Fernández-Veledo, Sonia}},
issn = {{2049-2618}},
keywords = {{Animal models; Glucose tolerance; Inflammation; Obesity; Probiotics; Succinate}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Microbiome}},
title = {{Orally administered <i>Odoribacter laneus</i> improves glucose control and inflammatory profile in obese mice by depleting circulating succinate}},
url = {{http://dx.doi.org/10.1186/s40168-022-01306-y}},
doi = {{10.1186/s40168-022-01306-y}},
volume = {{10}},
year = {{2022}},
}