Gut-brain signaling in energy homeostasis: the unexpected role of microbiota-derived succinate

Abstract

In the context of the obesity epidemic, dietary fibers that are found essentially in fruit and vegetables attract more and more attention, since they exert numerous metabolic benefits resulting in the moderation of body weight. Short-chain fatty acids, such as propionate and butyrate, produced through their fermentation by the intestinal microbiota, have long been thought to be the mediators of these benefits. In fact, propionate and butyrate were recently shown to activate intestinal gluconeogenesis, a function exerting metabolic benefits via its capacity of signaling to the brain by gastrointestinal nerves. Recently, succinate, the precursor of propionate in the bacterial metabolism, has also been shown to exert signaling properties, including the activation of intestinal gluconeogenesis.

Physiology and central carbon metabolism of the gut bacterium Prevotella copri

“…In contrast to Bacteroides spp., P. copri is not able to produce propionate and therefore generates succinate, acetate and formate as the only products of carbohydrate fermentation. In comparison with Bacteroides spp., this creates a different short chain fatty acid (SCFAs) composition that can be taken up by other microorganisms or by the host´s colonocytes (Fischbach and Sonnenburg, 2011;Tremaroli and Bäckhed, 2012;Vadder and Mithieux, 2018). This crossfeeding in turn can probably promote or repress specific microbial species or even alter intracellular signals of colonocytes (Schauber, 2003;den Besten et al, 2013;Corrêa-Oliveira et al, 2016).…”

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…Succinate, a metabolite produced in the human body but also by the gut microbiota, is described as the major intermediary in the citric acid cycle, where it stands between succinyl-CoA and fumarate in the carbohydrate metabolism but the gut-microbiota produced succinate is classically described as an intermediate of the propionate synthesis [57]. Succinate has been increased in hypertension, ischemic heart disease, and T2D, but also in obesity, which is associated with elevated plasma levels of succinate concomitant with impaired glucose metabolism [227] Alterations in circulating succinate levels were associated with specific metagenomics signatures linked to energy production and carbohydrate metabolism [64]. It has been related with an antilipolytic action in adipose tissue through the succinate receptor 1 (SUCNR1), inhibiting the release of fatty acid from adipocytes.…”

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening

“…Evidence from translational studies also supports a role for gut microbiota alterations in IR development, consistent with parallel alterations in plasma metabolites known to be modulated by the gut microbiota (15). However, conclusions about which specific bacterial species inhabiting the human gut are responsible for disrupting glucose homeostasis are contradictory across human and animal studies (14,(16)(17)(18). To address these issues, we aimed to acquire a better understanding of the childhood microbiome and its association with metabolic complications underlying obesity.…”