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

Serena C, Ceperuelo-Mallafré V, Keiran N, et al. The ISME Journal(2018)

Speaker: Si-Xuan Xie (謝思萱)                                Time: 13:10~14:00, May.23.2018

Commentator: Dr. Ching-Hao Teng (鄧景浩)       Place: Room 601

Abstract:

Cardiovascular disease (CVD) is a collective term used to describe heart and blood vessel disorder that leading cause of death worldwide.[1] CVD usually shows as coronary artery disease, atherosclerosis, and hypertension, with obesity playing an important role as a risk factor. There are more studies paying attention to Gut microbiota-related metabolites as potential clinical biomarkers and as therapeutic targets. Circulating succinate is a metabolite produced by the host and microbiota that increased in hypertension, ischemic heart disease, and type 2 diabetes.[2] The previous study has shown that the tricarboxylic acid intermediate succinate is concentrated in body fluids under conditions of hypoxia and inflammation and serves as a metabolic signal.[3]

The authors analyzed systemic levels of succinate in obesity and found it has a relationship with gut microbiome. And then, they explored the association between circulating succinate and specific metagenomic signature in cross-sectional. Obesity was associated with elevated levels of circulating succinate, and this increase was associated with a specific change in gut microbiota. Statistical data indicates that 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 the main determinant of plasma succinate. The authors also observed that modification of gut microbiota by dietary weight loss intervention reduces circulating succinate levels. In the spontaneous evolution after good dietary advice, the succinate alternation levels were linked with a specific gut metagenomic signature with the independence of body weight change. The data here uncover succinate as a potential microbiota-derived metabolite related to CVD risk.

References:

1. Vedanthan R, Fuster V. Urgent need for human resources to promote global cardiovascular health. Nat Rev Cardiol. 2011;8:114–7.
2. Aguiar CJ, Rocha-Franco JA, Sousa PA, Santos AK, Ladeira M, Rocha-Resende C, et al. Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation. Cell Commun Signal. 2014;12:78.
3. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature. 2013;496:238–42.