Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota.

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succi...

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Detalles Bibliográficos
Autores: Serena, Carolina, Ceperuelo-Mallafré, Victoria, Keiran, Noelia, Queipo-Ortuño, Maria Isabel, Bernal, Rosa, Gomez-Huelgas, Ricardo, Urpi-Sarda, Mireia, Sabater, Mónica, Pérez-Brocal, Vicente, Andrés-Lacueva, Cristina, Moya, Andres, Tinahones, Francisco J, Fernández-Real, Jose Manuel, Vendrell, Joan, Fernández-Veledo, Sonia
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17575
Acceso en línea:http://hdl.handle.net/20.500.12105/17575
Access Level:acceso abierto
Palabra clave:Adult
Aged
Bacteria
Biomarkers
Cross-Sectional Studies
Diabetes Mellitus, Type 2
Female
Gastrointestinal Microbiome
Humans
Male
Middle Aged
Obesity
Phylogeny
Prospective Studies
Succinic Acid
Descripción
Sumario:Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk.