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ISME J. 2018 Jun;12(7):1642-1657. doi: 10.1038/s41396-018-0068-2. Epub 2018 Feb 12.

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

Author information

1
Unitat de Recerca, Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain.
2
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
3
Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario de Málaga Virgen de la Victoria, Universidad de Málaga, 29010, Málaga, Spain.
4
CIBER de Obesidad y Nutrición (CIBERObN), Instituto de Salud Carlos III, Madrid, Spain.
5
Servicio de Medicina Interna, IBIMA, Hospital Regional Universitario de Málaga, 29010, Málaga, Spain.
6
Biomarkers and Nutrimetabolomics Laboratory, Nutrition, Food Science and Gastronomy Department, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, 08028, Spain.
7
CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, 28028, Spain.
8
Department of Diabetes Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Girona, Spain.
9
Genomics and Health Area, Foundation for the Promotion of Sanitary and Biomedical Research (FISABIO), València, Spain.
10
CIBER de Epidemiology y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
11
Institute of Integrative Systems Biology, Universitat de València, València, Spain.
12
Unitat de Recerca, Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain. jvo@comt.es.
13
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. jvo@comt.es.
14
Universitat Rovira i Virgili, Tarragona, Spain. jvo@comt.es.
15
Unitat de Recerca, Hospital Universitari de Tarragona Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain. sonia.fernandezveledo@gmail.com.
16
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. sonia.fernandezveledo@gmail.com.

Abstract

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.

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