Author, as appears in the article.: Huber-Ruano, Isabel; Calvo, Enrique; Mayneris-Perxachs, Jordi; Rodriguez-Pena, M-Mar; Ceperuelo-Mallafre, Victoria; Cedo, Lidia; Nunez-Roa, Catalina; Miro-Blanch, Joan; Arnoriaga-Rodriguez, Maria; Balvay, Aurelie; Maudet, Claire; Garcia-Roves, Pablo; Yanes, Oscar; Rabot, Sylvie; Grimaud, Ghjuvan Micaelu; De Prisco, Annachiara; Amoruso, Angela; Fernandez-Real, Jose Manuel; Vendrell, Joan; Fernandez-Veledo, Sonia
Department: Medicina i Cirurgia Eng. Electrònica, Elèctrica i Automàtica
URV's Author/s: Ceperuelo Mallafré, Maria Victoria / Miró Blanch, Joan / Vendrell Ortega, Juan José / Yanes Torrado, Óscar
Keywords: Triggers Succinate Sp nov. Signal Probiotics Obesity Microbiota Metabolism Inflammation Homeostasis Glucose tolerance Cells Animal models
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 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.
Thematic Areas: Microbiology (medical) Microbiology Medicina i General medicine Ciências biológicas i
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: oscar.yanes@urv.cat victoria.ceperuelo@urv.cat joan.miro@estudiants.urv.cat juanjose.vendrell@urv.cat
Author identifier: 0000-0003-3695-7157 0000-0002-4460-9761 0000-0003-3179-0554 0000-0002-6994-6115
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01306-y
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Microbiome. 10 (135): 135-
APA: Huber-Ruano, Isabel; Calvo, Enrique; Mayneris-Perxachs, Jordi; Rodriguez-Pena, M-Mar; Ceperuelo-Mallafre, Victoria; Cedo, Lidia; Nunez-Roa, Catalina; (2022). Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate. Microbiome, 10(135), 135-. DOI: 10.1186/s40168-022-01306-y
Article's DOI: 10.1186/s40168-022-01306-y
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications