The Role of Succinate in the Regulation of Intestinal Inflammation

Connors, Jessica; Dawe, Nick; Limbergen, Johan Van

doi:10.3390/nu11010025

Cited by 228 publications

(202 citation statements)

References 81 publications

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“…The role of succinate in the metabolic regulation of immune cells has been extensively reviewed by others [13,[33][34][35]; yet, despite significant progress in recent years, further research is necessary to build a complete picture of both intracellular and extracellular functions of succinate, not only in immune cells Succinate is then released into the cytosol and the extracellular space, where it can act as a signaling metabolite. (right) Succinate is also a catabolic metabolite of microbial carbohydrate fermentation.…”

Section: Succinate a Metabolite With Pleiotropic Functionsmentioning

confidence: 99%

“…In a generally healthy status, colonic and cecal concentrations of SCFAs range from 1 to 3 mM, whereas in circulation the concentrations of these metabolites are in the micromolar range. At the systemic level, acetate is the most abundant SCFA (5-200 μM), followed by propionate and butyrate (≤12-13 μM) [5,34]. By comparison, succinate is detected at a relatively low concentration in the gut lumen, likely related to its conversion to propionate by cross-feeding between different gut bacteria [59].…”

Section: Microbiota-derived Succinate In Health and Diseasementioning

confidence: 99%

“…In the context of disease, several studies have revealed a clear association between gut microbiota disturbances, linked for example to antibiotic-induced dysbiosis [63,64], motility disturbances [65] and specially IBD [34,66,67], and succinate accumulation in the gut lumen. More specifically, there is a wealth of evidence, both in mice and humans, demonstrating that IBD causes an increase in fecal succinate, which has been related to disease activity [68][69][70][71].…”

Section: Microbiota-derived Succinate In Health and Diseasementioning

confidence: 99%

See 2 more Smart Citations

Gut microbiota-derived succinate: Friend or foe in human metabolic diseases?

Fernández‐Veledo

Vendrell

2019

Rev Endocr Metab Disord

207

147

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There is now a wealth of evidence showing that communication between microbiota and the host is critical to sustain the vital functions of the healthy host, and disruptions of this homeostatic coexistence are known to be associated with a range of diseases including obesity and type 2 diabetes. Microbiota-derived metabolites act both as nutrients and as messenger molecules and can signal to distant organs in the body to shape host pathophysiology. In this review, we provide a new perspective on succinate as a gut microbiota-derived metabolite with a key role governing intestinal homeostasis and energy metabolism. Thus, succinate is not merely a major intermediary of the TCA traditionally considered as an extracellular danger signal in the host, but also a byproduct of some bacteria and a primary cross-feeding metabolite between gut resident microbes. In addition to maintain a healthy microbiome, specific functions of microbiota-derived succinate in peripheral tissues regulating host nutrient metabolism should not be rule out. Indeed, recent research point to some probiotic interventions directed to modulate succinate levels in the intestinal lumen, as a new microbiota-based therapies to treat obesity and related co-morbidities. While further research is essential, a large body of evidence point to succinate as a new strategic mediator in the microbiota-host cross-talk, which might provide the basis for new therapeutically approaches in a near future.

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Section: Succinate a Metabolite With Pleiotropic Functionsmentioning

confidence: 99%

Section: Microbiota-derived Succinate In Health and Diseasementioning

confidence: 99%

Section: Microbiota-derived Succinate In Health and Diseasementioning

confidence: 99%

See 1 more Smart Citation

Gut microbiota-derived succinate: Friend or foe in human metabolic diseases?

Fernández‐Veledo

Vendrell

2019

Rev Endocr Metab Disord

207

147

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“…[ 80 ] Succinate is known to induce superoxide production and mucosa damage in colon, [ 81,82 ] and its physiological concentration in the intestinal contents and feces is around 1–3 m m . [ 83 ] Thus, one might speculate that the suppressing effect of succinate observed on colonic proliferation might be due to toxicity resulting from the high dose used in this study (30 mL of 100 m m solution each day). [ 80 ]…”

Section: Gut Microbial Metabolites and Intestinal Stem Cell Activitiesmentioning

confidence: 99%

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

2020

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Microorganisms that colonize the gastrointestinal tract, collectively known as the gut microbiota, are known to produce small molecules and metabolites that significantly contribute to host intestinal development, functions, and homeostasis. Emerging insights from microbiome research reveal that gut microbiota‐derived signals and molecules influence another key player maintaining intestinal homeostasis—the intestinal stem cell niche, which regulates epithelial self‐renewal. In this review, the literature on gut microbiota‐host crosstalk is surveyed, highlighting the effects of gut microbial metabolites on intestinal stem cells. The production of various classes of metabolites, their actions on intestinal stem cells are discussed and, finally, how the production and function of metabolites are modulated by aging and dietary intake is commented upon.

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“…For succinate, we focused on the reductive tricarboxylic acid (TCA) cycle, as it produces the major end product of energy metabolism in anaerobic microorganisms. Many bacteria have incomplete TCA cycles and 11 are commensal obligate anaerobes, including Bacteroides spp., which use a branched TCA cycle to support fumarate respiration [27,28]. The end product of fumarate reduction, succinate, is secreted into the extracellular environment.…”

Section: Sagsmentioning

confidence: 99%

Single-cell genomics of uncultured bacteria reveals dietary fiber responders in the mouse gut microbiota

Chijiiwa

Hosokawa

Kogawa

et al. 2019

Preprint

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BackgroundThe gut microbiota can have dramatic effects on host metabolism; however, current genomic strategies for uncultured bacteria have several limitations that hinder their ability to identify responders to metabolic changes in the microbiota. In this study, we describe a novel singlecell genomic sequencing technique that can identify metabolic responders at the species level without the need for reference genomes, and apply this method to identify bacterial responders to an inulin-based diet in the mouse gut microbiota. ResultsInulin feeding changed the mouse fecal microbiome composition to increase Bacteroides spp., and increased microbial metabolic function resulted in increased succinate concentrations in the mouse intestine. Using our massively parallel single-cell genome sequencing technique, named SAG-gel platform, we obtained 346 single-amplified genomes (SAGs) from mouse gut microbes before and after dietary inulin supplementation. After quality control, the SAGs were classified as 267 bacteria, spanning two phyla, four classes, seven orders, and 14 families, and 31 different strains of SAGs were graded as high-and medium-quality draft genomes. From these, we have successfully obtained the genomes of the dominant inulin responders, Bacteroides spp., and identified their polysaccharide utilization loci and their specific metabolic pathways for succinate production. ConclusionsOur single-cell genomics approach generated a massive amount of SAGs, enabling functional analysis of uncultured bacteria in the intestinal microbiome and consideration of host responses. This enabled us to estimate metabolic lineages involved in the bacterial 2 fermentation of dietary fiber and metabolic outcomes such as short-chain fatty acid production in the intestinal environment based on the fibers ingested. The technique allows the in-depth isolation and characterization of uncultured bacteria with specific functions in the microbiota, and could be exploited to improve human and animal health. BackgroundThe gut microbiota plays a crucial role in the control of host physiology and metabolism through the release and transformation of metabolites like short-chain fatty acids (SCFAs) [1,2]. Many studies have demonstrated that dietary fiber supplementation can modulate gut microbiota composition and promote SCFA production [3][4][5]. This dietary fiber metabolism is particularly important for non-digestible inulin-type fructans classified as prebiotics, which are substrates that promote the growth of beneficial microorganisms in the gut [6][7][8][9][10][11][12]. Thus, to enhance the benefits of dietary fiber to the host, it is important to identify inulin responders in the complex microbiome community of the host intestine, and characterize their mechanisms of inulin fermentation and potential for SCFA production.Recently developed metagenomic approaches can provide comprehensive microbial profiling and putative functions using 16S rRNA gene amplicon sequencing and shotgun metagenome sequencing. These methods have enabled the ...

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The Role of Succinate in the Regulation of Intestinal Inflammation

Cited by 228 publications

References 81 publications

Gut microbiota-derived succinate: Friend or foe in human metabolic diseases?

Gut microbiota-derived succinate: Friend or foe in human metabolic diseases?

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

Single-cell genomics of uncultured bacteria reveals dietary fiber responders in the mouse gut microbiota

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