Articles producció científica> Medicina i Cirurgia

Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate

  • Dades identificatives

    Identificador: imarina:9280939
    Autors:
    Huber-Ruano, IsabelCalvo, EnriqueMayneris-Perxachs, JordiRodriguez-Pena, M-MarCeperuelo-Mallafre, VictoriaCedo, LidiaNunez-Roa, CatalinaMiro-Blanch, JoanArnoriaga-Rodriguez, MariaBalvay, AurelieMaudet, ClaireGarcia-Roves, PabloYanes, OscarRabot, SylvieGrimaud, Ghjuvan MicaeluDe Prisco, AnnachiaraAmoruso, AngelaFernandez-Real, Jose ManuelVendrell, JoanFernandez-Veledo, Sonia
    Resum:
    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.
  • Altres:

    Autor segons l'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
    Departament: Medicina i Cirurgia Eng. Electrònica, Elèctrica i Automàtica
    Autor/s de la URV: Ceperuelo Mallafré, Maria Victoria / Miró Blanch, Joan / Vendrell Ortega, Juan José / Yanes Torrado, Óscar
    Paraules clau: Triggers Succinate Sp nov. Signal Probiotics Obesity Microbiota Metabolism Inflammation Homeostasis Glucose tolerance Cells Animal models
    Resum: 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.
    Àrees temàtiques: Microbiology (medical) Microbiology Medicina i General medicine Ciências biológicas i
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: oscar.yanes@urv.cat victoria.ceperuelo@urv.cat joan.miro@estudiants.urv.cat juanjose.vendrell@urv.cat
    Identificador de l'autor: 0000-0003-3695-7157 0000-0002-4460-9761 0000-0003-3179-0554 0000-0002-6994-6115
    Data d'alta del registre: 2024-10-12
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01306-y
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Microbiome. 10 (135): 135-
    Referència de l'ítem segons les normes 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
    DOI de l'article: 10.1186/s40168-022-01306-y
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2022
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Microbiology,Microbiology (Medical)
    Triggers
    Succinate
    Sp nov.
    Signal
    Probiotics
    Obesity
    Microbiota
    Metabolism
    Inflammation
    Homeostasis
    Glucose tolerance
    Cells
    Animal models
    Microbiology (medical)
    Microbiology
    Medicina i
    General medicine
    Ciências biológicas i
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