Targeted interventions aimed at reducing circulating succinate levels in a subject, and kits and methods for determining the effectiveness of such interventions

Abstract

The present invention relates to kits suitable for determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject, in particular the ratio of (Prevotellaceae + Veillonellaceae) / (Odoribacteriaceae + Clostridiaceae), or for determining the level of succinate in a sample of body fluids from a subject. The invention also relates to a method for determining whether a targeted intervention aimed at reducing circulating succinate levels in a subject has been effective. Finally, the invention relates to targeted interventions for use in the prevention and / or treatment of a disease associated with elevated circulating succinate levels in a patient.

Description

Targeted interventions aimed at reducing circulating succinate levels in a subject, and kits and methods for determining the effectiveness of such interventions Field of Invention The present invention relates to targeted interventions aimed at reducing circulating succinate levels in a subject. The invention further relates to kits and a method for determining the effectiveness of such interventions. Background of the Invention Cardiovascular disease (CVD) is a collective term used to describe disorders of the heart and blood vessels and is the leading cause of death worldwide. In developed countries, CVD commonly manifests as coronary artery disease, atherosclerosis, and hypertension, with central obesity playing an increasingly important role as a risk factor. The generation of reactive oxygen species and the subsequent ramifications have been associated with the progression of CVD. Elevated levels of circulating succinate have also been detected in several high-risk CVD states such as hypertension (Sadagopan et al., 2007, Am. J. Hypertens. 20:1209-1215), ischemic heart disease (Aguiar et al., 2014, Cell Commun. Signal. 12:78) and type 2 diabetes mellitus (T2DM) (Guo et al., 2017, Nat. Commun. 8:15621; Sadagopan et al., 2007, Am. J. Hypertens. 20:1209-1215; Toma et al., 2008, J. Clin. Invest. 118:2526-2534; van Diepen et al., 2017, Diabetologia 60:1304-1313). In these scenarios, extracellular succinate is thought to signal through its related receptor SUCNR1 / GPR91, with pathological implications in hypertrophic cardiomyopathy (Aguiar et al., 2014, Cell Commun. Signal. 12:78), metabolic diseases related to obesity (McCreath et al., Diabetes.April 2015; 64(4):1154-67), renin-induced hypertension (Toma et al., 2008, J. Clin. Invest. 118:2526-2534) and diabetic retinopathy (Ariza et al., 2012, Front. Endocrinol. (Lausanne) 3: 22). Therefore, considering these subsequent effects, the reduction of the Reducing circulating succinate levels appears to be an attractive strategy for treating various diseases, including cardiovascular disease (CVD) and CVD-related conditions. The succinate receptor has also been suggested as a promising drug target for counteracting or preventing cardiovascular and fibrotic defects (Ariza et al., 2012, Front. Endocrinol. (Lausanne) 3:22). Interestingly, the exact origin of circulating succinate remains unclear. In this regard, it has been suggested that damaged tissues may contribute to the succinate found in the circulation (Ariza et al., 2012, Front. Endocrinol. (Lausanne) 3:22; Deen and Robben, 2011, J. Am. Soc. Nephrol. 22:1416-1422). Consequently, there is a need in the field for effective interventions aimed at reducing circulating succinate levels in an individual. Brief Summary of the Invention The inventors have surprisingly found that succinate produced by gut microbiota bacteria is a key contributor to total circulating succinate levels. Furthermore, they have demonstrated that the ratio of succinate-producing to succinate-consuming bacteria, specifically the ratio of (Prevotellaceae + Velllonellaceae) to (Odoribacteriaceae + Clostridlaceae), measured in a stool sample from a subject, can be correlated with circulating succinate levels in that same subject. Therefore, in a first aspect, the invention relates to a kit comprising reagents suitable for determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject, wherein the kit comprises primer sets designed to hybridize specifically with the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, or wherein the kit comprises probes that hybridize specifically with the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, and wherein the primer sets or probes comprise at least the -310% of the total amount of reagents that make up the kit. In a second aspect, the invention relates to the use of the kit according to the first aspect of the invention to detect the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject. In a third aspect, the invention relates to a kit comprising reagents suitable for determining the level of succinate in a sample of body fluids from a subject, wherein the presence of succinate in said sample of body fluids above a predetermined threshold level provides a positive result, and wherein the presence of succinate in said sample of body fluids below a predetermined threshold level or the absence of succinate in said sample of body fluids provides a negative result. In a fourth aspect, the invention relates to the use of the kit according to the third aspect of the invention to determine whether the level of succinate in a sample of body fluids from a subject is above a threshold level. In another aspect, the invention relates to the use of a kit for determining whether a probiotic intervention aimed at reducing circulating succinate levels in a subject has been effective, the kit comprising reagents suitable for determining the level of succinate in a sample of body fluids from a subject, wherein a circulating succinate level in the subject's body fluid sample after the probiotic intervention that is lower than the circulating succinate level in the subject's body fluid sample before the probiotic intervention is indicative that the probiotic intervention has been effective, and wherein a circulating succinate level in the subject's body fluid sample after the probiotic intervention that is equal to or greater than the circulating succinate level in the subject's body fluid sample before the probiotic intervention is indicative that the probiotic intervention has not been effective. -4 In a further aspect, the invention relates to a method for determining whether a targeted intervention, aimed at reducing circulating succinate levels in a subject, has been effective, the method comprising: (a) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject before the targeted intervention, and (b) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject after the targeted intervention, wherein a ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject after the targeted intervention that is lower than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject before the targeted intervention is indicative that the targeted intervention has been effective,and in which a ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention equal to or greater than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample before the targeted intervention is indicative that the targeted intervention has not been effective. In yet another aspect, the invention relates to a dietary intervention or dietary product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In yet another aspect, the invention relates to a product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the product decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract, wherein the product is selected from the group consisting of a product - 5 pharmacological and a probiotic product. In another additional aspect, the invention relates to a product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the product decreases the patient's circulating succinate levels, wherein the product is selected from the group consisting of a pharmacological product and a probiotic product. In a final aspect, the invention relates to a probiotic product comprising an effective amount of succinate-consuming bacteria, wherein the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Phascolarctobacterium spp., Ruminococcus spp. and combinations thereof. Brief Description of the Figures of the Invention Figure 1A and Figure 1B show the decision tree for identifying prognostic factors for the optimal / altered metabolic profile. The classification and regression tree for the optimal / altered metabolic profile is based on age, body mass index (BMI), succinate, cholesterol, high-density lipoprotein cholesterol (HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), and type 2 diabetes (T2DM). The pie charts represent the proportion of patients who met the optimal (dark gray) or altered (light gray) criteria at each node of the tree. Figures 2A to 2D show that circulating succinate levels are increased in obesity and type 2 diabetes. (Figure 2A) Circulating plasma levels in lean, obese, and type 2 diabetic (T2DM) individuals. Data are expressed as median and interquartile range. Differences were analyzed using the Kruskal-Wallis test with Dunn's post hoc multiple comparisons test. *, p<0.0001 vs. lean. (Figure 2B) Positive correlation between succinate levels and IMG, insulin, glucose, HOMA-IR, and triglycerides using the entire cohort. (Figure 2C) Negative correlation between succinate levels and SAT ATGL, SAT ABHD5, SAT HSL, and SAT ZAG levels. (Figure 2D) Positive correlation between succinate levels and SAT HIF1A and SAT CD163. subcutaneous adipose tissue (subcutaneous adipose tissue). Statistical analyses for (Figure 2B), (Figure 2C) and - 6(Figure 2D): Spearman correlation analysis. Figures 3A to 3J show that the gut microbiota composition of obese individuals is associated with circulating succinate levels. (Figure 3A) Percentage incidence within the Bacteroidetes and Firmicutes families in non-obese and obese individuals. (Figure 3B) Differences between non-obese and obese individuals at the family level: ratio of the Prevotellaceae plus Veillonellaceae families / (Odoribacteriaceae plus C1 os tridaceae families) (fam[(PtV) / (O+C)]). (Figure 3C) Positive correlation between serum succinate levels and the fam[(P+V) / (O+C)] ratio. (Figure 3D) Positive correlation between serum succinate levels and circulating zonulin levels. (Figure 3E) Validation studies were performed using cohort III. Percentage of incidence within the Bacteroidetes and Firmicutes families in lean and obese individuals. (Figure 3F) Positive correlation between plasma levels of succinate and Veillonellaceae.(Figure 3G) Differences between lean and obese individuals in the fam[(W+V) / (O+C)] ratio in the cohort III study. (Figure 3H) Positive correlation between serum succinate levels and the log[(W+V) / (O+C)] ratio in the cohort III study. Data information: For (Figure 3A) and (Figure 3E), values ​​are expressed as mean ± SD. For (Figure 3B) and (Figure 3G), data are represented in box-and-whisker plot format (whiskers: minimum to maximum). Statistical analyses: Mann-Whitney U test. *, p<0.05 vs. non-obese or lean. For (Figure 3C), (Figure 3D), (Figure 3F), and (Figure 3H), Spearman or Pearson correlation analyses with Bonferroni adjustment were used. (Figure 31) Seventeen subjects with type 2 diabetes mellitus (T2D) (9 women and 4 men) were included in the study. The P+V / O+C ratio is 4.70 ±6.12.(Figure 3J) The graph shows the Spearman correlation between plasma levels of succinate and Odoribacteraceae for 26 plasma samples from obese diabetic patients. The subjects were enrolled at the Endocrinology Department of Bellvitge University Hospital (Barcelona, ​​Spain). Figures 4I to 4E show the weight loss induced by the dietary intervention or dietary product that modifies the specific gut microbiota and influences circulating succinate levels, (Figure 4A) Serum levels of circulating succinate at baseline and after a 12-week dietary intervention or dietary product - 7(12-wDI) from cohort IV. (Figure 4B) Percentage incidence within the Bacteroidetes and Firmicutes families in obese individuals at baseline and after 12-wDI. (Figure 4C) Positive correlation between the change in serum succinate levels ([succinate] from 12-wDI - [succinate] from baseline) and the change in Prevotellaceae ([% abundance of Prevotellaceae] from 12-wDI - [% abundance of Prevotellaceae] from baseline). (Figure 4D) Differences between baseline and 12-wDI in the fain[(P+V) / (O+C)] ratio. (Figure 4E) Positive correlation between the change in serum succinate levels ([succinate] from 12-wDI - [succinate] from baseline) and the change in the ratio of (fam[P+V / O+C] from 12-wDI - íam[(P+V) / (O+C)] from baseline). Data information: For (Figure 4A) and (Figure 4B), values ​​are expressed as mean ± SD. For (Figure 4D), data are represented in box and whisker plot format (whiskers: from minimum to maximum). Statistical analyses: Wilcoxon signed-rank test.*, p<0.05 vs. baseline. For (Figure 4C) and (Figure 4D), Spearman correlation analysis with Bonferroni adjustment was used. Figures 5A to 5E show the gut microbiota composition in non-obese and obese subjects in Cohort II. (Figure 5A) Firmicutes / Bacteroidetes ratio; (Figure 5B) richness index (number of OTUs) and (Figure 5C) diversity index (Shannon-Weaver) calculated in non-obese and obese individuals. (Figure 5D) Percentage incidence within the Bacteroidetes and Firmicutes genera in non-obese and obese individuals; (Figure 5E) Ratio at the genus level of [(Prevotella spp. plus Veillonella spp.) / (Odoribacter spp. plus Clostridium spp.)] (gene[(P+V) / (O+C)]) in non-obese and obese individuals. Data information: For (Figure 5A), (Figure 5B), (Figure 5C), and (Figure 5E), the data are represented in box and whisker plot format (whiskers: from minimum to maximum). For (Figure 5D), the values ​​are expressed as mean ± SD. Statistical analysis: Mann-Whitney U test. *, p<0.05 vs. non-obese. Figures 6A to 6E show the composition of the gut microbiota in cohort IV of the dietary intervention study, (Figure 6A) richness index (number of OTUs) and (Figure 6B) diversity index (Shannon-Weaver) (Figure 6C) Firmicutes / Bacteroidetes ratio calculated at baseline and at 12-wDI in obese individuals from cohort IV of - 8. Microbiota. (Figure 6D) Differences in the percentage of incidence within the genera Bacteroidetes and Firmicutes at baseline and at 12-wDI. (Figure 6E) Ratio at the genus level of (gen[(P+V) / (O+C)]) at baseline and at 12-wDI. Data information: For (Figure 6A), (Figure 6B), (Figure 6C), and (Figure 6E), the data are represented in box and whisker plot format (whiskers: minimum to maximum). For (Figure 6D), the values ​​are expressed as mean ± SD. Statistical analysis: Wilcoxon signed-rank test. *, p<0.05 vs. 12-wDI. Figure 7 shows metabolic genes related to succinate metabolism and the microbiota that metabolizes succinate. Differences in the genes encoding enzymes are shown between group 1 (the proportion of patients decreased at the end of follow-up) and group 2 (the proportion of patients increased at the end of follow-up). Data are represented in a scatter plot with mean and standard deviation. Statistical analysis: Mann-Whitney U test. Figure 8A and Figure 8B show the effect of *Odoribacter laneus* on the glucose tolerance test (GTT) in obese mice. C57 / B16 mice were fed a high-fructose diet for 16 weeks. The resulting obese mice were then treated daily with 100 µL of *Odoribacter laneus* at 1x109 CFU / mL in PBS + 1% glycerol (vehicle) via oral feeding through a gastric tube for 24 days. The glucose tolerance test (Figure 8A) was improved in animals treated with *Odoribacter laneus*. The area under the curve (AUC) is shown in Figure 8B. Detailed Description of the Invention As explained previously, the inventors have surprisingly found that succinate produced by gut microbiota bacteria is a key contributor to total circulating succinate levels. Furthermore, they have demonstrated that the ratio of succinate-producing to succinate-consuming bacteria, specifically the ratio of (Prevotellaceae + Veillonellaceae) to (Odoribacteriaceae + Clostridiaceae), measured in a stool sample from a subject, can be correlated with circulating succinate levels in that same subject. -9 Kits of the invention The inventors have developed kits to determine the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. Therefore, in a first aspect, the invention relates to a kit comprising reagents suitable for determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject, preferably wherein the kit comprises primer sets designed to hybridize specifically with the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, or wherein the kit comprises probes that hybridize specifically with the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, and wherein the primer sets or probes comprise at least 10% of the total amount of reagents forming the kit. In the context of the present invention, a kit is understood to be a product containing the various reagents for use according to the different applications and methods of the invention, packaged in a manner that allows for its transport and storage. Additionally, the kits used in the invention may contain instructions for the simultaneous, sequential, or separate use of the different components contained in the kit. These instructions may be in the form of printed material or on an electronic medium capable of storing instructions that can be read or understood, such as, for example, electronic storage media (e.g., tapes, magnetic disks), optical media (e.g., CD-ROM, DVD), or audio materials. Alternatively, the media may contain internet addresses that provide such instructions. In a preferred embodiment, the kit comprises primer sets designed to hybridize specifically to the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium. - 10 In another preferred embodiment, the kit comprises probes that specifically hybridize to the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium. As used herein, the term 16S rRNA gene refers to a bacterial gene encoding the component of the small 30S subunit of a prokaryotic ribosome that binds to the Shine-Dalgarno sequence. Sequence analysis of the 16S ribosomal RNA (rRNA) gene has been widely used to identify bacterial species and conduct taxonomic studies. Bacterial 16S rRNA genes typically contain nine hypervariable regions that demonstrate considerable sequence diversity among different bacterial species and can be used for species identification. Therefore, as used herein, the term 16S rRNA gene hypervariable regions refers to such sequences in the 16S ribosomal rRNA gene, which allow for the identification of a single bacterial species or differentiation among a limited number of different species or genera.In the context of the present invention, the hypervariable regions of the 16S rRNA gene allow the identification or differentiation of at least one succinate-producing bacterium and at least one succinate-consuming bacterium. The identification of these regions can be mediated by techniques well known to those skilled in the art. Non-limiting examples of such techniques include polymerase chain reaction (PCR) amplification, real-time polymerase chain reaction (RT-PCR), in situ hybridization (ISH), Northern blotting, or microalignment. In one particular embodiment, the hypervariable regions of the 16S rRNA gene are used to identify bacteria of the species Prevotella spp., Veillonella spp., Odoribacter spp., and / or Clostridium spp. In a preferred embodiment, the Prevotella spp. 16S rRNA gene comprises a sequence having at least 85%, at least 90%, at least 95%, at least 99%, or at least 100% identity with SEQ ID No: 1 (GenBank registration no: AB244770; version no: AB244770.1; date of last modification April 19, 2007). In a more preferred embodiment, the Prevotella spp. is Prevotella copri and the gene for 16S rRNA comprises the sequence with SEQ ID No: 1. In a preferred embodiment, the gene of -11 Veillonella spp. for 16S rRNA comprises a sequence having at least 90%, at least 95%, at least 99%, or at least 100% identity with SEQ ID No: 2 (Genbank registration no: EF108443; version no: EF108443.1, date of last modification January 3, 2011). In a more preferred embodiment, Veillonella spp. is Veillonella rogosae and the gene for 16S rRNA comprises the sequence with SEQ ID No: 2. In a preferred embodiment, the Odoribacter spp. gene for 16S rRNA comprises a sequence having at least 86%, at least 90%, at least 95%, at least 99%, or at least 100% identity with SEQ ID No: 3 (Genbank registration no: AB547648; version no: AB547648.1; date of last modification November 9, 2012). In a more preferred embodiment, the Odoribacter spp. is Odoribacter laneus and the gene for 16S rRNA comprises the sequence with SEQ ID No: 3. In a preferred embodiment, the Clostridium spp. genefor 16S rRNA comprises a sequence having at least 95%, at least 99%, or at least 100% identity with SEQ ID No: 4. In a more preferred embodiment, the Clostridium spp. is Clostridium ramosum and the gene for 16S rRNA comprises the sequence with SEQ ID No: 4 (Genbank registration no: AB627078; version no: AB627078.1, date of last modification November 9, 2012). As used herein, the term primer set refers to a set of RNA or DNA oligonucleotides (preferably approximately 15–35 bases) that specifically hybridizes to the hypervariable regions of the 16S rRNA gene and serves as a starting point for DNA synthesis. Primers are required for DNA polymerase-mediated amplification in a PCR-based reaction. The quantity, concentration, and / or relative average size of each amplicon can then be analyzed using techniques known to those skilled in the art. Non-limiting examples of such techniques include gel electrophoresis or RT-PCR-based techniques. It is also possible to sequence the target nucleic acid using these primers after further steps known to those skilled in the art. As used herein, the term probe refers to oligonucleotide sequences of DNA or RNA that hybridize by complementarity with a specific sequence. In other words, the probe hybridizes with a specific single-stranded nucleic acid (DNA or RNA) whose The 12-base sequence allows probe-target base pairing due to complementarity between the probe and the target. In a preferred embodiment, the resulting hybrid can be detected using techniques known to those skilled in the field. For example, the probe can be labeled with a marker, which may be radioactive or fluorescent molecules, and immobilized on a membrane or in situ. Commonly used markers are 32P (a radioactive isotope of phosphorus incorporated into the phosphodiester bond in the DNA probe) or digoxigenin, a non-radioactive antibody-based marker. DNA sequences or RNA transcripts that have moderate to high sequence similarity to the probe are then detected by visualizing the hybridized probe using autoradiography or other imaging techniques.Typically, either X-ray images of the filter are taken, or the filter is placed under UV light or a microscope for detection of the fluorescently labeled probe. The detection of sequences with moderate or high similarity depends on how rigorous the hybridization conditions were applied—high rigor, such as high hybridization temperature and low salt in the hybridization buffers, allows hybridization only between nucleic acid sequences that are very similar, while low rigor, such as lower temperature and high salt, allows hybridization when the sequences are less similar. As used herein, the term oligonucleotide refers to a single-stranded DNA or RNA molecule, preferably up to 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, or 13 bases in length (upper limit). The oligonucleotides of the invention are DNA or RNA molecules, preferably at least 2, at least 5, at least 10, at least 12, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, or at least 25 nucleotide bases in length (lower limit). The base length intervals can be combined in all different ways using the lower and upper limits mentioned above, for example, at least 2 and up to 30 bases, at least 10 and up to 15 bases, at least 5 and up to 15 bases, or at least 15 and up to 18 bases. As used herein, the term hybridize specifically refers to the conditions that allow the hybridization of two polynucleotides under very rigorous or moderately harsh conditions. - 13. Rigorous. The rigor of hybridization reactions can be easily determined by someone skilled in the technique and is generally an empirical calculation that depends on probe length, wash temperature, and salt concentration. In general, longer probes require higher temperatures for proper pairing, while shorter probes require lower temperatures. Hybridization generally depends on the ability of denatured DNA to re-pair when complementary strands are present in an environment below its melting temperature. The greater the desired degree of homology between the probe and the target sequence, the higher the relative temperature that must be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more rigorous, while lower temperatures would make them less so. See Brown T, Gene Cloning (Chapman & Hall, London, UK, 1995). In preferred embodiments, the primer assemblies or probes comprise at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% of the total amount of reagents comprising the kits of the invention. In one particular embodiment, the total amount of reagents comprising the kits of the invention refers to the total number of reagents in the kit. As used herein, the term succinate refers to a metabolite that is the anion of succinic acid, also known as butanedioate. It is an intermediate in the tricarboxylic acid (TCA) cycle and plays a crucial role in the generation of adenosine triphosphate (ATP) in the mitochondria. The chemical formula of succinate is C4H4O42-. As used herein, the expression circulating succinate or circulating succinate in a subject refers to the detectable succinate in a blood, plasma, or serum sample from a subject. As used herein, the expression "succinate-producing bacteria" refers to bacteria that produce and release succinate. In the context of the present invention, the expression "succinate-producing bacteria" also refers to bacteria that actively produce succinate and bacteria that do not actively produce succinate, provided that - 14 that the latter can produce and release succinate when environmental conditions permit (i.e., in the presence of appropriate substrates). In one particular embodiment, succinate-producing bacteria are bacteria that actively produce succinate. In another particular embodiment, succinate-producing bacteria are bacteria that do not actively produce succinate, provided they can produce and release succinate when environmental conditions permit (i.e., in the presence of appropriate substrates). A person skilled in the art could design an assay to determine whether a bacterium is a succinate-producing bacterium.In this example, the bacteria can be grown in culture medium for a predetermined time, and the conditioned culture medium can then be analyzed for the accumulation of succinate, which indicates that the bacteria are succinate-producing. Examples of succinate-producing bacteria are known in the art: Louis et al., 2014, Nat. Rev. Microbiol 12:661-672; Nakayama et al., 2017, Front. Microbiol. 8:197; Vogt et al., 2015, Anaerobe 34:106-115. Preferably, these bacteria are intestinal bacteria, meaning they can survive and multiply efficiently in a subject's intestine. In a preferred embodiment, these bacteria are selected from the group consisting of Prevotella spp., Veillonella spp., and Bacteroides spp. Paraprevotella spp., Succinovibrio spp., Ruminococcus spp., Fibrobacter succinogenes and combinations thereof.Ideally, the succinate-producing bacteria should belong to the families Prevotellaceae and Velllonellaceae. The Prevotellaceae family belongs to the phylum Bacteroidetes, class Bacteroidetes, and order Bacteroldales. It comprises four genera: Prevotella, Alloprevotella, Hallella, and Paraprevotella. The Velllonellaceae family belongs to the phylum Finoids, class Negativicutes, and order Selenomonadales. It includes six genera: Veillonella, Megasphaera, Dialister, Allisonella, Anaeroglobus, and Negativicoccus. Even more ideally, the succinate-producing bacteria should be a selected species from the group consisting of Prevotella copri, Prevotella intermedia, Prevotella nigrescens, Prevotella melaninogenica, Prevotella nanceensis, Veillonella rogosae, Veillonella atypica, and combinations thereof. Prevotella and Veillonela are both gram-negative bacteria. As used in this document, the expression bacteria that - 15. "Consuming succinate" refers to bacteria that consume succinate. In the context of the present invention, the expression "bacteria that consume succinate" refers equally to bacteria that actively consume succinate and bacteria that do not actively consume succinate, provided that the latter can consume succinate when environmental conditions permit (i.e., in the presence of succinate). In one particular embodiment, the bacteria that consume succinate are bacteria that actively consume succinate. In another particular embodiment, the bacteria that consume succinate are bacteria that do not actively consume succinate, provided that they can consume succinate when environmental conditions permit (i.e., in the presence of succinate). A person skilled in the art could design an assay to determine whether a bacterium is a succinate-consuming bacterium.In the example, the bacteria can be grown in culture medium containing succinate for a predetermined time. The conditioned culture medium can then be analyzed to determine the depletion of succinate in that medium and the accumulation of an end product such as butyrate, which is indicative that the bacteria are succinate-consuming. Examples of succinate-consuming bacteria are known in the art: Ferreyra et al., 2014, Cell Host Microbe. 16:770-777; Reichardt et al., 2014, ISME J. 8:1323-1335. Preferably, these bacteria are intestinal bacteria, meaning they can survive and multiply efficiently in a subject's intestine. In a preferred embodiment, these bacteria are selected from the group consisting of Odoribacter spp., Clostridium spp., Phascolarctobacterium succinatutens, and combinations thereof.More preferably, the bacteria that consume succinate are those of the families Odoribacteriaceae and Clostridiaceae. The family Odoribacteriaceae belongs to the phylum Bacteroidetes, the class Bacteroideae, and the order Bacteroidales. The family Clostridiaceae belongs to the phylum Firmicutes, the class Clostridia, and the order Clostridiales. Even more preferably, the bacteria that produce succinate are a selected species from the group consisting of Odoribacter laneus; Odoribacter splanchnicus; Clostridium scinderdens; Clostridium symbiosum; Clostridium perfringens; Clostridium citroniae; Clostridium hathewayi; Clostridium ramosum, and combinations thereof. Odoribacter are Gram-negative bacteria, while Clostridium are Gram-negative. - 16 gram-positive bacteria. As used herein, the expression "ratio of succinate-producing bacteria to succinate-consuming bacteria" refers to the result of dividing the total number of, or a specific subset of, succinate-producing bacteria by the total number of, or a specific subset of, succinate-consuming bacteria. In a preferred embodiment, the ratio of succinate-producing bacteria to succinate-consuming bacteria to be determined is the ratio of (Prevotellaceae + Veillonellaceae) / (Odoribacteriaceae + Clostridiaceae). As used herein, the term feces refers to solid or semi-solid fecal residues of food that could not be digested in the intestine. In one particular embodiment, a fecal sample is collected from a subject after defecation. As used herein, the term subject or patient refers to all animals classified as mammals and includes, but is not limited to, domestic and farm animals, primates, and humans, e.g., humans, non-human primates, cows, horses, pigs, sheep, goats, dogs, cats, or rodents. Preferably, the subject is a male or female of any age or race. In a second aspect, the invention relates to the use of the kit according to the first aspect of the invention to detect the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject, preferably the ratio of (Prevotellaceae + Veillonellaceae) / (Odoribacteriaceae + Clostridiaceae). In a third aspect, the invention relates to a kit comprising reagents suitable for determining the level of succinate in a sample of body fluids from a subject, wherein the presence of succinate in said sample of body fluids above a predetermined threshold level provides a positive result, and wherein the presence of succinate in said sample of body fluids below a predetermined threshold level or the absence of succinate in said sample of body fluids provides a negative result. - 17As used herein, the expression "reagents suitable for determining the level of succinate in a body fluid" refers to reagents that can directly or indirectly detect the presence of succinate in a sample. Non-limiting examples include reagents that can detect the presence of NADPH or Pi, which can be generated in the presence of succinate. A non-limiting example of a reaction in which the presence of succinate results in the generation of Pi is as follows: succinate + ATP + CoA converted by succinyl-CoA synthase to succinyl-CoA + ADP + Pi. In one particular example, the color intensity at 450 nm of the reaction product is directly proportional to the concentration of succinate in the sample. In a preferred embodiment, at least one of the reaction products is detectable by a color change. In another preferred embodiment, the kit comprises a succinate-specific enzyme. In preferred embodiments, the reagents suitable for determining the succinate level in a body fluid each comprise at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% of the total amount of reagents comprising the kits of the invention. In one particular embodiment, the total amount of reagents comprising the kits of the invention refers to the total number of reagents in the kit. As used herein, the term body fluid or subject's body fluid refers to a biological fluid obtained from a subject's body. Non-limiting examples of body fluid include blood, saliva, cerebrospinal fluid, urine, feces, bone marrow, a nipple aspirate, plasma, serum, cerebrospinal fluid (CSF), stool, a buccal or oropharyngeal swab, a surgical body fluid specimen, or a sample obtained from a body fluid biopsy. Therefore, as used herein, the expression body fluid specimen refers to an isolated sample of a subject's body fluid. Methods for isolating body fluid specimens are well known to those skilled in the art. In one particular embodiment, the body fluid is urine, blood, or saliva; preferably urine. In a preferred embodiment where the body fluid is urine, the succinate threshold level is preferably between 5 and 15 JM, more preferably between 8 and 12 JM, and even lower. - 18preferably 10 |JM. In a preferred embodiment in which the body fluid is blood, the threshold level of succinate is preferably between 50 and 70 (JM, more preferably between 55 and 65 pM, and still more preferably 60 |JM. As used herein, the term threshold level refers to the concentration level of at least one specific analyte that indicates a subject is classified as having an abnormal metabolic profile associated with an increased risk of developing metabolic disorders such as diabetes, and is therefore prone to such metabolic disorders if the patient's analyte level is above this threshold level. Threshold levels are typically calculated using the CART (classification tree and regression) statistical method to determine characteristic succinate values ​​for subjects with an altered metabolic profile or subjects with an optimal metabolic profile.The main elements of CART are: (a) rules for splitting data at a node based on the value of a variable; (b) stopping rules for deciding when a branch is terminal and cannot be split further; and (c) finally, a prediction for the target variable at each terminal node. In one particular embodiment, the kit is a home testing kit. As used herein, the term home testing kit refers to a testing kit that allows a subject to perform the test at home, for example, a urine test that indicates a positive or negative result by a color change or other means such as a digital output. The home test is designed for use by anyone without medical expertise, and as such, urine-based tests are ideal. Home testing kits are sensitive to the presence of succinate in a sample and change color or otherwise indicate when the particular test detects succinate sensitivity above the threshold. In one particular embodiment, the kit comprises at least one test strip. As used herein, a test strip is a strip of the type used to place a sample at a particular point that initiates a color test or other indicator test of a succinate sample. In the newer type of test, the test strip could also be of the digital type, in which an indicator display presents a message such as - 19 such as the presence or absence of a high succinate content rather than a simple color change. While "strip" in one embodiment means a single device, for the purposes of this invention, other embodiments covered by the term "test strip" include two or more devices joined together to facilitate the placement of urine on both at the same time. In yet another embodiment, it refers to two or more separate strips designed to be used simultaneously to obtain the results of the more and less sensitive tests at the same time. In a fourth aspect, the invention relates to the use of the kit according to the third aspect of the invention to determine whether the succinate level in a sample of a subject's body fluids is above a threshold level. In one particular embodiment, the subject's body fluid sample is a blood sample, a urine sample, or a stool sample. The succinate threshold levels are as defined above in this document. In another aspect, the invention relates to the use of a kit for determining whether a probiotic intervention aimed at reducing circulating succinate levels in a subject has been effective, the kit comprising reagents suitable for determining the level of succinate in a sample of body fluids from a subject, wherein a circulating succinate level in the subject's body fluid sample after the probiotic intervention that is lower than the circulating succinate level in the subject's body fluid sample before the probiotic intervention is indicative that the probiotic intervention has been effective, and wherein a circulating succinate level in the subject's body fluid sample after the probiotic intervention that is equal to or greater than the circulating succinate level in the subject's body fluid sample before the probiotic intervention is indicative that the probiotic intervention has not been effective. Method for determining whether a targeted intervention has been effective The inventors have demonstrated that an intervention that decreases the ratio of succinate-producing bacteria to bacteria that -20% consumption of succinate in the gastrointestinal tract of a subject can be effective in reducing circulating succinate levels in a subject. Therefore, in a further aspect, the invention relates to a method for determining whether a targeted intervention, aimed at reducing circulating succinate levels in a subject, has been effective, the method comprising: (a) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject before the targeted intervention, and (b) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject after the targeted intervention, wherein a ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject after the targeted intervention that is lower than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject before the targeted intervention is indicative that the targeted intervention has been effective,and in which a ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention is equal to or greater than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample before the targeted intervention is indicative that the targeted intervention has not been effective. In one particular embodiment, the subject is obese. In another particular embodiment, the subject has type 2 diabetes mellitus. In yet another particular embodiment, the subject is obese and has type 2 diabetes mellitus. According to the present invention, the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention is considered to be lower than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample before the targeted intervention when the ratio of succinate-producing bacteria to -21 bacteria that consume succinate in the subject's stool sample after the targeted intervention is at least 1.5%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 110%, at least 120%, at least 130%, at least 140%, at least 150% or lower than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample prior to the targeted intervention. Similarly, in the context of the present invention, the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention is considered to be greater than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample before the targeted intervention when the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention is at least 1.5%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 110%, at least 120%,at least 130%, at least 140%, at least 150% or more greater than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample prior to the targeted intervention. In the context of the present invention, the targeted intervention, aimed at reducing circulating succinate levels in a subject, has been effective when the circulating succinate levels in the subject after the targeted intervention are at least 1.5%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least -2295%, at least 100%, at least 110%, at least 120%, at least 130%, at least 140%, at least 150% or more lower than the circulating succinate levels in the subject before the targeted intervention. Similarly, a targeted intervention aimed at reducing circulating succinate levels in a subject has not been effective when the circulating succinate levels in the subject after the targeted intervention are equal to or less than 1.5%, at least 2%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 110%, or at least 120%. at least 130%, at least 140%, at least 150% or more higher than the circulating succinate levels in the subject before the targeted intervention. The term "intervention aimed at reducing circulating succinate levels in a subject" refers to any action performed on a subject with the objective of reducing circulating succinate levels in that subject. Preferably, such interventions comprise the administration of specific compounds or combinations of compounds, such as nutrients or combinations of nutrients, specific pharmaceutical or biological compounds. In a particular embodiment, the targeted intervention is selected from the group consisting of a dietary intervention or dietary product, a pharmacological intervention, and a probiotic intervention. Targeted interventions of the invention The targeted intervention may consist of a dietary intervention or a dietary product. Therefore, in a further aspect, the invention relates to a dietary intervention or a dietary product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In another aspect, the invention relates to the use of a dietary intervention or a dietary product for the manufacture of a medicament in the -23Prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In yet another aspect, the invention relates to a method for treating and / or preventing a disease associated with increased levels of circulating succinate in a patient, wherein the method comprises subjecting the patient to a dietary intervention or providing the subject with a dietary product, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In yet another aspect, the invention relates to the use of a dietary intervention or a dietary product for the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In another aspect, the invention relates to a dietary intervention or a dietary product for use in the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In another aspect, the invention relates to the use of a dietary intervention or a dietary product for the manufacture of a medicament in the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In yet another aspect, the invention relates to a method for the -24 treatment and / or prevention of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury and diabetic nephropathy, wherein the method comprises subjecting the patient to a dietary intervention or a dietary product, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In yet another aspect, the invention relates to the use of a dietary intervention or a dietary product for the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the method comprises subjecting the patient to a dietary intervention, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. As used herein, the term prevention refers to the prophylaxis of a disease or condition, that is, preventing or stopping the development or even occurrence of a disease or condition in its initial stage or before its onset. As used herein, the term treatment refers to the eradication, elimination, reversal, relief, modification, or control of the progression of a disease or condition after its onset and before or after the appearance of clinical signs.More precisely, the progression of the disease or condition is considered controlled if beneficial or desired clinical outcomes appear, including, but not limited to, reduction of symptoms, reduction of the duration of the disease or condition, stabilization of the pathological condition associated with the disease or condition (specifically, avoidance of further deterioration), delay in the progression of the disease or condition, and / or improvement of the pathological condition associated with the disease or condition and its remission (both partial and total). In one particular embodiment, the patient is obese. In another particular embodiment, the subject has type 2 diabetes mellitus. In yet another particular embodiment, the subject is obese and has type 2 diabetes mellitus. -25As used herein, the term obese refers to a subject suffering from obesity, where, as used herein, the term obesity is defined as indicated by the World Health Organization (WHO). According to the WHO, obesity and overweight refer to a state in which the obese or overweight subject has an abnormal or excessive accumulation of fat that may impair their health. More specifically, the WHO defines overweight and obesity using the body mass index (BMI) as follows, where BMI is defined as a person's weight in kilograms divided by the square of their height in meters (kg / m2): Overweight is a state of a subject with a BMI greater than or equal to 25 kg / m2; Obesity is a state of a subject with a BMI greater than or equal to 30 kg / m2. As used herein, the expression "disease associated with increased levels of circulating succinate in a patient" refers to a disease that is known to occur concurrently with elevated levels of circulating succinate, which have been associated with disease progression. Non-limiting examples of such diseases are hypertension (Sadagopan et al., 2007, Am. J. Hypertens. 20:1209-1215), ischemic heart disease (Aguiar et al., 2014, Cell Commun. Signal. 12:78), type 2 diabetes mellitus (T2DM) (Guo et al., 2017, Nat. Commun. 8:15621; Sadagopan et al., 2007, Am. J. Hypertens. 20:1209-1215; Toma et al., 2008, J. Clin. Invest. 118:2526-2534; 2014, Cell Commun. 12:78), obesity-related metabolic diseases (McCreath et al., Diabetes. April 2015; 64(4):1154-67), renin-induced hypertension (Toma et al., 2008, J. Clin. Invest.118:2526-2534), and diabetic retinopathy (Ariza et al., 2012, Front. Endocrinol. (Lausanne) 3: 22). In addition, elevated levels of succinate have been described in autoimmune diseases. Succinate has been detected abundantly in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) (Borestein et al., 1982, Arthritis Rheum. 25:947-953; Kim et al., 2014, PLoS One. 9:e97501), and a metabolic profiling study has identified succinate as the most differentially expressed metabolite in RA compared to other autoimmune diseases. -26arthropathies (Kim et al., 2014, PLoS One. 9:e97501). In one particular embodiment, the disease associated with increased circulating succinate levels in a patient is selected from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy. In a preferred embodiment, the disease is obesity. As used herein, the term "elevated circulating succinate levels" refers to a circulating succinate level that is elevated relative to a reference value. In one particular embodiment, the reference value is obtained from a healthy subject. In another particular embodiment, the reference value is obtained from subjects who do not have a medical history of a disease associated with elevated circulating succinate levels, preferably from the diseases listed above. In a particular embodiment, circulating succinate levels are considered to be increased relative to circulating succinate levels in a reference sample when they increase by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 120%, at least 150%, at least 200% or more relative to a reference sample. As used herein, the expression "decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria" refers to interventions in which the ratio of succinate-producing bacteria to succinate-consuming bacteria is decreased by decreasing the total number of succinate-producing bacteria, increasing the total number of succinate-consuming bacteria, or by a combination of both decreasing the total number of succinate-producing bacteria and increasing the total number of succinate-consuming bacteria. As used herein, the term patient gastrointestinal tract or digestive tract generally refers to the digestive structures extending from the mouth to the anus, but does not include the -27 accessory glandular organs such as the liver, bile ducts, or pancreas. The digestive tract is a system of organs within humans and other animals that takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. The mouth, esophagus, stomach, small intestine, and large intestine are part of the digestive tract. The digestive tract contains thousands of different bacteria in its intestinal microflora. In a particular embodiment, the term digestive tract in the context of the present invention refers specifically to the small intestine and / or the large intestine. In a particular embodiment, the ratio of succinate-producing bacteria to succinate-consuming bacteria that is to be reduced is the ratio of (Prevotellaceae + Veíllonellaceae) / (Odoribacteriaceae + Clostrídíaceae). As used herein, the term dietary intervention refers to an act or group of acts performed on a subject that involve following a specific diet of interest. As used herein, the term dietary product refers to a complete set of meals to be provided to the subject and comprising at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, or 100% of the subject's total food intake. In one particular embodiment, the dietary product comprises at least breakfast, lunch, and dinner. In one particular embodiment, the dietary product comprises one meal per day, two meals per day, three meals per day, four meals per day, or five or more meals per day.As used herein, the term diet refers to instructions regarding the foods an individual must consume to achieve the absorption of a predetermined amount of specific nutrients. In some cases, the diet may also include instructions regarding the type and amount of fluids the individual is to consume and the type and duration of physical exercise the individual must perform to achieve the same absorption of specific nutrients. Non-exhaustive examples of diets include a low-calorie diet or a Mediterranean diet. In one particular embodiment, the intervention comprises a hypocaloric diet, preferably a hypocaloric diet characterized by: -28 Fats make up 35-40% of total daily calorie intake; and carbohydrates make up 40-45% of total daily calorie intake; in which the dietary intervention or dietary product is administered for at least 12 weeks, and in which the dietary intervention or dietary product is optionally administered in combination with a physical exercise program. As used herein, the expression "total daily calorie intake" refers to the sum of the calories from each food item consumed by the individual during a given day. To calculate the daily percentage of fat, the calories from fat are divided by the total calories and then multiplied by 100. To calculate the daily percentage of carbohydrates, the calories from carbohydrates are divided by the total calories and then multiplied by 100. In a preferred embodiment, the diet is a Mediterranean diet. In the context of the present invention, a Mediterranean diet is characterized by a proportionately high consumption of olive oil, legumes, unrefined cereals, fruits, and vegetables; moderate to high consumption of fish; moderate consumption of dairy products (primarily cheese and yogurt); moderate consumption of wine; and low consumption of non-fish meat products. In a preferred embodiment, the diet includes extra virgin olive oil and nuts. In a preferred embodiment, 8-10% of the total fat consists of saturated fatty acids. In a preferred embodiment, the carbohydrates are low-glycemic index carbohydrates. Low-glycemic index carbohydrates are characterized by a GI range of 55 or less.Examples of low-GI carbohydrates include fructose; beans (black, pinto, kidney, lentil, peanut, chickpea); small seeds (sunflower, flax, pumpkin, poppy, sesame, hemp); nuts, cashews, most whole grains (durum wheat / spelt / kamut wheat, millet, oats, rye, rice, barley); most vegetables, most sweet fruits (peaches, strawberries, mangoes); tagatose; mushrooms; and chili peppers. In a preferred embodiment, protein is 20% of total daily calorie intake. In a preferred embodiment, the dietary intervention or dietary product is administered for at least 12 weeks, for at least 16 -29 weeks, for at least 20 weeks, for at least 24 weeks, for at least one year, for at least two years, for at least three years, for at least four years, for at least five years, or indefinitely. In a preferred embodiment in which the dietary intervention or dietary product is optionally administered in combination with a physical exercise program, the duration of the physical exercise is at least 45 minutes per day for the duration of administration of the dietary product. In the context of the present invention, a hypocaloric diet is a diet in which the subject consumes fewer calories than they expend throughout the day. Therefore, to design a hypocaloric diet, it is necessary to calculate the subject's daily calorie requirement: that is, the basal metabolic rate (the energy expenditure of the body for normal functioning) must be determined, and the calories the subject expends through daily physical activity (i.e., walking, climbing stairs, etc.) and sports activity (i.e., training) must be added. Basal metabolic rate can be calculated using different methods and depends on various factors, such as a person's height and weight. It is also influenced by factors such as age, muscle mass, body temperature, etc. Basal metabolic rate can be calculated, for example, using the Harris-Benedict equation: Basal metabolism in men (metric): 66.473 + (13.751 x weight in kg) + (5.0033 x height in cm) - (6.7550 x age in years) Basal metabolism in women (metric): 655.1 + (9.463 x weight in kg) + (1.8 x height in cm) - (4.6756 x age in years) Therefore, in a preferred embodiment, daily calorie consumption is reduced by 200 kcal compared to total daily calorie requirements; in a preferred embodiment, daily calorie consumption is reduced by 300 kcal compared to total daily calorie requirements; in a preferred embodiment, daily calorie consumption is reduced by 400 kcal compared to total daily calorie requirements; in a preferred embodiment, daily calorie consumption is reduced by 500 kcal compared to total daily calorie requirements; in a preferred embodiment, daily calorie consumption is reduced by 600 kcal compared to total daily calorie requirements. Targeted intervention can also refer to an intervention -30pharmaceutical or a probiotic intervention. Therefore, in one aspect, the invention relates to a product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the product decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract, wherein the product is selected from the group consisting of a pharmaceutical product and a probiotic product. In a particular aspect, the invention also relates to a product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the product decreases the patient's circulating succinate levels, wherein the product is selected from the group consisting of a pharmaceutical product and a probiotic product. In another aspect, the invention relates to the use of a pharmacological product or a probiotic product for the manufacture of a medicament in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In a particular aspect, the invention also relates to the use of a pharmacological product or a probiotic product for the manufacture of a medicament in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the product decreases the patient's circulating succinate levels. In yet another aspect, the invention relates to a method for treating and / or preventing a disease associated with increased levels of circulating succinate in a patient, wherein the method comprises administering a pharmacological product or a probiotic product to the patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. In a particular aspect, the invention also relates to a method for treating and / or preventing a disease associated with increased levels of circulating succinate in a patient, wherein the method comprises administering a pharmacological product or a probiotic product to the patient, wherein the product decreases the -31 levels of circulating succinate in the patient. In another aspect, the invention relates to a product for use in the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the product decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract, wherein the product is selected from the group consisting of a pharmacological product and a probiotic product.In one particular aspect, the invention also relates to a product for use in the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the product decreases the patient's circulating succinate levels, wherein the product is selected from the group consisting of a pharmacological product and a probiotic product. In another aspect, the invention relates to the use of a pharmacological product or a probiotic product for the manufacture of a medicament in the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract.In one particular aspect, the invention also relates to the use of a pharmacological product or a probiotic product for the manufacture of a medicament in the prevention and / or treatment of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the product decreases the patient's circulating succinate levels. In yet another aspect, the invention relates to a method for the -32 treatment and / or prevention of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury and diabetic nephropathy, wherein the method comprises administering a pharmacological product or a probiotic product to the patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract.In one particular aspect, the invention also relates to a method for the treatment and / or prevention of a selected disease from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy, wherein the method comprises administering a pharmacological product or a probiotic product to the patient, wherein the product decreases the patient's circulating succinate levels. The terms and expressions prevention, treatment, decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria, decreases circulating succinate levels, and gastrointestinal tract are as defined above. As used herein, the term pharmacological intervention refers to an act or group of acts performed on a subject that includes administering a drug product of interest to that subject. As used herein, the term drug product or drug composition refers to a product or composition with a chemical formulation that has been adapted to deliver a predetermined dose of one or more therapeutic agents for the treatment of a specific disease or condition. Such agents are normally in combination with a pharmaceutically acceptable carrier in such drug product or composition. As used herein, the term carrier refers to a diluent or excipient with which the active ingredient or active agent is administered.Such pharmaceutical carriers may be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. These are preferably used as aqueous carriers. -33 Aqueous saline solutions and aqueous solutions of dextrose and glycerol, particularly for injectable solutions. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences by E.W. Martin, 1995. Preferably, the carriers of the invention are approved by a state or federal regulatory agency or are listed in the United States Pharmacopeia or another generally recognized pharmacopoeia for use in animals, and more particularly in humans. The vehicles and excipients necessary to manufacture the desired dosage form of the pharmaceutical composition of the invention will depend, among other factors, on the selected dosage form. Such dosage forms of the pharmaceutical composition will be manufactured according to conventional methods known to those skilled in the art.A review of different methods of administering active ingredients, the excipients to be used, and the procedures for producing them can be found in the Treatise on Galenic Pharmacy, C. Faulí i Trillo, Luzán 5, SA de Ediciones, 1993. Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions, or emulsions) composition for oral, topical, or parenteral administration. In addition, the pharmaceutical composition may contain stabilizers, suspensions, preservatives, surfactants, and similar agents as needed. As used herein, the term probiotic intervention refers to an act or group of acts performed on a subject that includes administering a probiotic product of interest to that subject. As used herein, the expression probiotic product or probiotic composition refers to a product or composition containing a probiotic agent, where the probiotic agent is understood to be live microorganisms that confer a health benefit on the host when administered in adequate amounts. Probiotics exert their beneficial effects when they are live. Preferably, such health benefits are specific to, and even more preferably form the basis of, the treatment or prevention of a specific disease or condition. Typically, probiotics are bacterial populations.There are four basic ways to consume probiotics: as a concentrated culture added to a beverage (e.g., fruit juice, etc.). -34inoculated in prebiotic fibers, as a food supplement in freeze-dried cellular dosage forms (e.g. powder, capsules, tablets, etc.) and inoculated in milk-based foods. In one particular embodiment, the patient is an obese patient. The term obese is used as defined above. In one particular embodiment, the disease associated with increased circulating succinate levels in a patient is selected from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury, and diabetic nephropathy. In a particular embodiment, the ratio of succinate-producing bacteria with respect to succinate-consuming bacteria to be reduced is the ratio of {Prevotellaceae + Velllonellaceae) / (Odoribacteriaceae + Clostrlddiaceae). In one particular embodiment, the drug product specifically targets succinate-producing bacteria, and preferably the drug product is selected from the group consisting of an antibiotic, an antibacterial antibody, and a bacteriophage. The expression "specifically targets succinate-producing bacteria" refers to a drug product that selectively reduces the population of succinate-producing bacteria relative to the total bacteria. Selection methods for determining whether a drug product selectively reduces the population of succinate-producing bacteria can be readily devised by someone skilled in the art.In one particular example, a screening method to determine whether a specific drug product selectively reduces the population of succinate-producing bacteria may involve culturing Prevotella in a medium containing the specific drug product and comparing the growth of Prevotella with the growth of other types of bacteria. As used herein, the term antibiotic refers to a type of antimicrobial product or composition used in the treatment and prevention of bacterial infections. They can either destroy or inhibit the growth of bacteria. They can be administered as a drug product or composition. In one particular embodiment, the antibiotic is a specific antibiotic effective against bacteria. -35 Gram-negative bacteria. In a preferred embodiment, the antibiotic specific against Gram-negative bacteria is a beta-lactam antibiotic. In a more preferred embodiment, the antibiotic specific against Gram-negative bacteria is a monobactam antibiotic. In a still more preferred embodiment, the antibiotic specific against Gram-negative bacteria is aztreonam. As used herein, the term antibacterial antibody refers to (a) an antibody-antibiotic conjugate (AAC) that combines key attributes of an antibody and an antibiotic, or (b) a monoclonal antibacterial antibody (DiGiandomenico and Sellman, Current Opinion in Microbiology 2015, 27: 78-85). An AAC has three components: an antibiotic payload to destroy bacteria, an antibody to direct the delivery of the payload to bacteria, and a linker that attaches the payload to the antibody. AACs are potentially effective in treating specific bacterial infections. One non-limiting example of bacteria that has been shown to be targeted by an AAC is Staphylococcus aureus.On the other hand, monoclonal antibacterial antibody technology refers to the use of bacteria-specific monoclonal antibodies (mAbs) to reduce the bacterial load of those specific bacteria. Passive immunization of individuals with mAbs selected for their superior functional activity can both neutralize bacterial virulence and take advantage of the host's immune response against specific bacteria. In this regard, bacterial capsular polysaccharides have been successfully selected as vaccine antigens (i.e., against Streptococcus pneumoniae and Haemophilus influenzae), and specific antitoxin antibodies are also being developed. Surface antigens are considered a promising target for the discovery of antibacterial antibodies.The key activities of bacterial surface-specific monoclonal antibodies (mAbs) are coupling the host immune system through complement fixation and opsonophagocytic destruction (OPK). The general methodology for producing monoclonal antibodies using hybridomas is well understood. Immortal cell lines that produce antibodies can also be created using techniques other than fusion, such as direct transformation of B lymphocytes with oncogenic DNA or transfection with Epstein-Barr virus. See, for example, M. Schreier et al. -36al., Hybridoma Techniques (1980); Hammerling et al., Monoclonal Antibodies And T-cell Hybridomas (1981); Kennett et al., Monoclonal Antibodies (1980). Monoclonal antibodies against Prevotella are commercially available (i.e., DMAB9450 anti-Prevotella Intermedia monoclonal antibody against the OMZ 248 strain of Prevotella Intermedia from chronic human periodontitis, by Creative Diagnostics). As used herein, the term bacteriophage refers to a virus that infects and replicates within a bacterium. Phages replicate within the bacterium after injecting their genome into the bacterial cytoplasm. They have been used for over 90 years as an alternative to antibiotics. In one particular embodiment, the bacteriophage selectively infects Prevotella. In a preferred embodiment, the bacteriophage selectively infects Prevotella ruminicola. In a more preferred embodiment, the bacteriophage is selected from the group consisting of φΒΗΒΟΙ, φΒΗΒ02 (Klieve et al. 1989 Api. Environ. Microbiol. 55: 1630-4) and φ4ΑΒ.29 (Gregg K et al. 1994 Microbiology 140: 2109-14). In another preferred embodiment, the bacteriophage selectively infects Bacteroides fragilis, which is also a known succinate producer. In a more preferred embodiment, the bacteriophage is selected from the group consisting of φB124-14 and φB40-8 (Ogilvie et al.).2013 Nature Communications 4, 2420). In one particular embodiment, the probiotic product comprises succinate-consuming bacteria. In a preferred embodiment, the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Clostridium spp., Phascolarctobacterium spp., Ruminococcus spp., and combinations thereof. In a particular embodiment, the probiotic product is a combination of Odoribacter spp. and Clostrldium spp.; a combination of Odoribacter spp. and Ruminococcus spp.; a combination of Odoribacter spp. and Phascolarctobacterium spp.; a combination of Clostrldium spp. and Ruminococcus spp.; a combination of Clostrldium spp and Phascolarctobacterium spp.; a combination of Ruminococcus spp. and Phascolarctobacterium spp.; a combination of Odoribacter spp., Clostrldium spp. and Ruminococcus spp.; a combination of Odoribacter spp., Clostrldium spp., and Phascolarctobacterium spp.; a combination of Odoribacter spp., Ruminococcus spp., and -37Phascolarctobacterium spp.; a combination of Clostridium spp., Ruminococcus spp., and Phascolarctobacterium spp.; or a combination of Odoribacter spp., Clostridium spp., Ruminococcus spp., and Phascolarctobacterium spp. In a preferred embodiment, Odoribacter spp. is selected from the group consisting of Odoribacter laneus, Odoribacter splanchnicus, and combinations thereof. In a more preferred embodiment, the Odoribacter spp. is Odoribacter laneus. In a still more preferred embodiment, the Odoribacter spp. is the DSM22474 strain of Odoribacter laneus. In a preferred embodiment, Clostridium spp. is selected from the group consisting of Clostridium scindens, Clostridium symbiosum, Clostridium perfringens, Clostridium citroniae, Clostridium hathewayi, Clostridium ramosum, and combinations thereof. In a preferred embodiment, Phascolarctobacterium spp. is selected from the group consisting of Phascolarctobacterium succinatutens and Phascolarctobacterium faecium. In a preferred embodiment, Ruminococcus spp. It is Ruminococcus bromii. In another aspect, the invention relates to a product for use in a method for improving an altered metabolic profile in a patient, wherein the product decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract, and wherein the product is selected from the group consisting of a dietary product, a pharmaceutical product, and a probiotic product. All terms and embodiments described elsewhere herein are equally applicable to this aspect of the invention. As used herein, the term altered metabolic profile refers to a set of threshold values ​​for various parameters associated with the risk of developing metabolic pathologies such as diabetes. In one particular embodiment, the altered metabolic profile is associated with an increased risk of suffering from a selected metabolic dysfunction from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic cardiomyopathy, ischemia / reperfusion injury, and diabetic nephropathy. The characteristic values ​​of an altered metabolic profile in the context of the present invention are as follows: Insulin > 25 pLU / ml - Glucose > 100 (mg / dl) -38HOMA-IR >3,21 - Triglycerides > 1.7 (mM) The threshold values ​​for glucose and triglycerides are defined by the American Diabetes Association, the American Heart Association, or the International Diabetes Federation to define metabolic syndrome. However, in the context of the invention, these thresholds do not necessarily refer to metabolic syndrome. The threshold value for HOMA-IR (Homeostatic Model of Insulin Resistance Index) has been described elsewhere (Ceperuelo-Mallafré et al., J Clin Endocrinol Metab. May 2014; 99(5): E908-19; Cardona F. et al., Clin Chem. October 2006; 52(10): 1920-5). As used herein, the term "improving an altered metabolic profile in a patient" refers to actions aimed at lowering the values ​​of parameters associated with the risk of developing metabolic disorders such as diabetes. In one embodiment, the values ​​of the parameters associated with the risk of developing metabolic disorders are lowered below the threshold values ​​that define the altered metabolic profile. In a preferred embodiment, all values ​​of the parameters associated with the risk of developing metabolic disorders are lowered below the threshold values ​​that define the altered metabolic profile. In a final aspect, the invention relates to a probiotic product comprising an effective quantity of succinate-consuming bacteria, wherein the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Phascolarctobacterium spp., Ruminococcus spp., and combinations thereof. The terms probiotic product and succinate-consuming bacteria are used as defined above. In a particular embodiment, the probiotic product is a combination of Odoribacter spp. and Clostridium spp.; a combination of Odoribacter spp. and Ruminococcus spp.; a combination of Odoribacter spp. and Phascolarctobacteríum spp.; a combination of Clostridium spp. and Ruminococcus spp.; a combination of Clostridium spp. and Phascolarctobacteríum spp.; a combination of Ruminococcus spp. and Phascolarctobacteríum spp.; a combination of Odoribacter spp., Clostridium -39spp. and Ruminococcus spp.; a combination of Odoribacter spp., Clostridium spp. and Phascolarctobacterium spp.; a combination of Odoribacter spp., Ruminococcus spp. and Phascolarctobacterium spp.; a combination of Clostridium spp., Ruminococcus spp. and Phascolarctobacterium spp.; or a combination of Odoribacter spp., Clostridium spp., Ruminococcus spp. and Phascolarctobacterium spp. In a preferred embodiment, the Odoribacter spp. is selected from the group consisting of Odoribacter laneus, Odoribacter splanchnicus, and combinations thereof. In a more preferred embodiment, the Odoribacter spp. is Odoribacter laneus. In a still more preferred embodiment, the Odoribacter spp. is the DSM22474 strain of Odoribacter laneus. In a preferred embodiment, the Clostridium spp. is selected from the group consisting of Clostridium scindens, Clostridium symbiosum, Clostridium perfringens, Clostridium citroniae, Clostridium hathewayi, Clostridium ramosum, and combinations thereof. In a preferred embodiment, the Phascolarctobacterium spp. is selected from the group consisting of Phascolarctobacterium succinatutens and Phascolarctobacterium faecium. In a preferred embodiment, Ruminococcus spp. It is Ruminococcus bromii. The invention also reveals the following aspects: 1. A kit comprising reagents suitable for determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject, wherein the kit comprises primer sets designed to hybridize specifically with the hypervariable regions of the 16S rRNA genome in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, or wherein the kit comprises probes that hybridize specifically with the hypervariable regions of the 16S rRNA genome in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, and wherein the primer sets or probes comprise at least 10% of the total amount of reagents forming the kit. 2. Use of the kit according to aspect 1 to detect the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject. 3. The kit according to aspect 1 or the use according to aspect 2, wherein the ratio of succinate-producing bacteria to succinate-consuming bacteria is the ratio of (Prevotellaceae + Veillonellaceae) / (Odoribacteriaceae + Clostridiaceae). 4. A method for determining whether a targeted intervention, aimed at reducing circulating succinate levels in a subject, has been effective, the method comprising: (a) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject before the targeted intervention, and (b) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject after the targeted intervention, wherein a ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject after the targeted intervention that is lower than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject before the targeted intervention is indicative that the targeted intervention has been effective,and in which a ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention equal to or greater than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample before the targeted intervention is indicative that the targeted intervention has not been effective. 5. The aspect 4 method, in which the targeted intervention is selected from the group consisting of a dietary intervention or dietary product, a pharmacological intervention, and a probiotic intervention. 6. A dietary intervention or dietary product for use in the prevention and / or treatment of a disease associated with levels -41 increased circulating succinate in a patient, in which the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract. 7. The dietary intervention or dietary product for use according to aspect 6, wherein the intervention comprises a hypocaloric diet characterized in that: Fat makes up 35-40% of total daily calorie intake; and carbohydrates make up 40-45% of total daily calorie intake; in which the dietary intervention or dietary product is administered for at least 12 weeks, and in which the dietary intervention or dietary product is optionally administered in combination with a physical exercise program. 8. A product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate, wherein the product decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract, wherein the product is selected from the group consisting of a pharmacological product and a probiotic product. 9. The dietary intervention or dietary product for use according to any one of aspects 6 or 7, or the product for use according to aspect 8, in which the patient is obese. 10. The dietary intervention or dietary product for use according to any one of aspects 6, 7 or 9, or the product for use according to any one of aspects 8 or 9, wherein the disease associated with increased levels of circulating succinate in a patient is selected from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury and diabetic nephropathy. 11. The dietary intervention or dietary product for use according to any one of aspects 6-7 or 9-10, or the product for use according to -42any one of aspects 8 to 10, wherein the ratio of succinate-producing bacteria to succinate-consuming bacteria is the ratio of (Prevotellaceae + Velllonellaceae) / (Odoribacteriaceae + Clostridiaceae). 12. The product for use according to any one of aspects 8 to 11, wherein the drug product specifically targets succinate-producing bacteria, and wherein the drug product is selected from the group consisting of an antibiotic, an antibacterial antibody, and a bacteriophage. 13. The product for use according to any one of aspects 8 to 12, wherein the probiotic product comprises succinate-consuming bacteria. 14. The product for use according to aspect 13, wherein the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Clostridium spp., Phascolarctobacterium succinatetens and combinations thereof. 15. A probiotic product comprising an effective amount of succinate-consuming bacteria, wherein the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Clostridium spp., Phascolarctobacterium succinatutens and combinations thereof. The following invention is described in this document by means of the following examples, which should be interpreted as merely illustrative and not limiting to the scope of the invention. EXAMPLES Materials and methods Study design and patients The present study comprised five different clinical substudies to achieve the following objectives: 1) to analyze circulating succinate levels in lean, obese, and diabetic subjects using a study -43 cross-sectional, cohort I; 2) examine the relationship between intestinal microbiota and succinate (discovery cohort II and confirmatory cohort III); 3) establish the connection between circulating succinate and intestinal microbiota (dietary intervention study cohort IV and follow-up study cohort V). All studies were conducted in accordance with the principles of the Declaration of Helsinki. All volunteers received information about their participation in the study and provided written informed consent. The studies were approved by the respective review boards of the local Ethics Committees of the participating hospitals. Inclusion criteria for all subjects: (1) white men and women; (2) INC range from thin to obese (adequately represented in each group); (3) absence of underlying pathology on physical examination and tests other than those associated with excess weight or diabetes; (4) signed informed consent for participation in the study. Exclusion criteria for all subjects: (1) severe systemic disease unrelated to obesity such as cancer, severe renal or hepatic disease; (2) systemic diseases with intrinsic inflammatory activity; (3) history of liver disease (chronic active hepatitis or cirrhosis) and / or abnormal liver function (ALT and / or AST 3 times above the upper limit of normal); impaired renal function (creatinine greater than 1.4 mg / dl in women and 1.5 mg / dl in men); (4) pregnant and lactating women; (5) vegetarians or subjects on an irregular diet; (6) patients with severe eating disorders; (7) clinical symptoms and signs of infection in the previous month; (8) chronic anti-inflammatory treatment with steroidal and / or non-steroidal anti-inflammatory drugs; (9) prior antibiotic treatment in the last 3 months; (10) significant psychiatric history; (11) uncontrolled alcoholism or drug addiction. Cohort I of cross-sectional study Design: single-point observational study. Participants: Ninety-one subjects (49 women and 42 men) were included in the cross-sectional study (30 lean, 41 obese and 20 patients with T2DM). -44Obesity was classified according to World Health Organization (WHO) criteria. Patients with type 2 diabetes mellitus (T2DM) were diagnosed according to American Diabetes Association criteria with stable metabolic control in the previous 6 months, as defined by stable glycated hemoglobin levels. No patients were treated with insulin; 60% were treated with metformin, 20% with sulfonylureas, and less than 15% with dipeptidyl peptidase-4 inhibitors. Subjects were enrolled at the Endocrinology Department of Joan XXIII University Hospital (Tarragona, Spain). Intervention: All patients fasted overnight before subcutaneous adipose tissue (SAT) and blood collection. SAT was obtained during scheduled, non-urgent surgical procedures, including laparoscopic surgery for hiatal hernia repair or cholecystectomy. SAT samples were washed in phosphate-buffered saline (PBS) and immediately frozen in liquid nitrogen at -80°C, or used immediately for fractionation. For SAT fractionation, freshly prepared SAT was cut into small cubes (10–30 mg), washed in PBS, and incubated in medium 199 (Gibco, Grand Island, NY) plus 4% bovine serum albumin and 2 mg / mL type I collagenase (Sigma-Aldrich, St. Louis, MO) for 1 h in a 37°C agitated water bath. Anthropometric and clinical variables are summarized in Table 1. -45Table 1. Anthropometric and clinical characteristics in cohort I. Related to figure 1 (AB). Cross-sectional study (cohort I) Lean Obese T2EM n 30 41 20 Age (years) 49 (40.75-63.25) 56 (41.50-70) 65 (56.75-70.75) Sex (female / male) 14 / 16 23 / 18 12 / 8 BMI (kg / m2) 23.75 (22-24.88) 30.52 (27.75-33.66)** 29.06 (27-31.03) Insulin (pU / ml) 5.65 (2.55-8.42) 9.87 (4.45-16.07)* 13.31 (9.42-21.64) Glucose (mg / dl) 89 (83-106) 100 (88.75-108.5)* 139.5 (109.75-162.75)## HCMA IR 1.50 (0.98-2.40) 2.55 (1.19-3.45) 4.96 (3.19-3.31)## TAS 119.40 ± 6.07 138.13 ± 18.95* 142.5 ± 20 TAD 67 (60-75) 80 (70-80) 80 (62.5-83) Cholesterol (irM) 4.86 ± 1.23 4.94 ± 1.05 4.58 ± 1.08 HDL Cholesterol (miM) 1.35 (1.04- 1.61) 1.23 (1.02-1.52) 1.11 (0.98-1.47) Triglycerides (niM) 0. 97 (0.861.09) 1.23 (0.74-1.66) 1.83 (1.38-2.26)# sIL6 (pg / ml) 1.62 (1.33- 2.77) 1.63 (1.02-2.57) 1.70 (1.03-2.44) sTNFRl (ng / ml) 1.92 ± 0.53 2.02 ± 0.35 2.23 ± 0.39 STNFR2 (ng / ml) 2.92 ± 0.89 3.60 ± 1.17 5.43 ± 1.07## Data are presented as mean ± SD or median (25-75 years), as appropriate. Differences were analyzed using one-way ANOVA with Bonferroni correction (normal distribution) or Kruskal-Wallis test with Dunn's post-hoc multiple comparisons test (data not normally distributed). BMI: body mass index; HOMA-IR: homeostatic model assessment of insulin resistance index; SBP: systolic blood pressure; DBP: diastolic blood pressure. *p<0.05, **p<0.01 vs. lean; #p<0.05, ##p<0.01 vs. obese. -46 Discovery Cohort II Design: single-point observational study. Participants: Twenty women (10 lean and 10 obese) were included in the cross-sectional study. Obesity was classified according to QMS criteria. Subjects were enrolled in outpatient surgery at the Endocrinology Department of the Virgen de la Victoria University Hospital in Málaga (Málaga, Spain). Study participants did not receive antibiotics, probiotics, prebiotics, or any other medical treatment that influences the gut microbiota during the 3 months prior to the start of the study. Intervention: All patients had fasted overnight before blood and stool collection. Anthropometric and clinical variables are summarized in Table 2. Confirmatory Cohort III Design: single-point observational study. Participants: Seventeen subjects (10 women and 7 men) were included in the study (9 lean and 8 obese). Obesity was classified according to QMS criteria. Subjects were enrolled in the Service of Endocrinology at the Dr. Josep Trueta University Hospital (Girona, Spain). Study participants did not receive treatment with antibiotics, probiotics, prebiotics, or any other medical treatment that influences the gut microbiota during the 3 months prior to the start of the study. Intervention: All patients had fasted overnight before blood and stool collection. Anthropometric and clinical variables are summarized in Table 2. Table 2. Anthropometric and analytical characteristics in cohort studies II and III. Related to figure 2 (AD). Discovery Cohort II Confirmatory Cohort III Non-obese Obese P Thin Obese P η 10 10 9 8 Age 41.6 14.06 43.4 15.5 6 ns 50.22 1 9.11 52.88 1 7.3 ns Sex (women / men) 10 / 0 10 / 0 ns 4 / 5 6 / 2 ns Weight (kg) 71.1 (65.2 84.5) 108.7 (93.8 121.5) 0.001 64.8 (sepsis,6) 122.25 (115.52 125.62) 0.001 Waist (cm) 92.7 9 15.45 124.1 11 15.39 <0.001 81.89 1 9.75 126.12 1 14.47 <0.00 1 Hip (cm) 103.913.76 124.2511 5.6 0.002 98.77 1 5.87 134 1 14.48 0.002 BMI 25.69 1 1.6 38.8216, 58 <0.001 23.2 (20.2524.9) 46.35 (38.1548.07) <0.00 1 Insulin (μυ / ml) 8.79 (7.9910.40) 19.6 (16.5233.88) <0.001 2.62 1 1, 92 18.4 1 12 <0.00 1 Glucose (mg / dl) 92 (82.75- 93) 112 (97.75124.25) <0.001 85 1 5.96 99.75 1 11.2 <0.00 1 HCMA IR 1.9810.28 713.33 0.001 0.58 1 0.44 4.33 1 2.59 0.001 TAS 108.5 (104.5114.2) 121 (119.5136) 0.001 121 1 10.68 139 1 16.96 0.001 TAD 61.5 (5671) 75.5 (65.75- 79) 0.015 66.67 1 11.42 78.5 1 7.43 0.015 Cholesterol (mg / dl) 188.6 1 9.47 210.2 1 43.83 ns 200.33 1 29.71 186.75 1 58.83 ns HDL cholesterol (mg / dl) 65.7 1 15.50 43.6 1 8.66 0.001 61.89 1 17.49 52.25 1 17.5 0.001 LDL cholesterol (mg / dL) 112.86 1 16.1 131.26 1 31.82 ns 72.22 1 28.97 103 1 65.58 ns TG (mg / dl) 85.2 1 32.04 199.2 1 46.7 <0.001 121 1 10.68 139 1 16.96 <0.00 1 Zonulin (ng / ml) 500.87 1 44.61 869.33 1 199.01 0.03 634.481 224.32 834.08 1 315.25 0.04, Data are presented as mean ± SD or median (25-75 years), as appropriate. Differences were analyzed using the t-test for independent samples (normal distribution) or the Mann-Whitney U test (data not normally distributed). BMI: body mass index; HOMA-IR: homeostatic model assessment of insulin resistance index; SBP: systolic blood pressure; DBP: diastolic blood pressure; TG: triglycerides. A p-value of less than 0.05 was considered significant. Cohort IV of dietary intervention or dietary product Design: intervention study. Participants: Nine obese women (a subsample from the registered study ISRCTN88315555) were included in the study. Subjects were enrolled in outpatient surgery at the Endocrinology Department of the Virgen de la Victoria University Hospital in Málaga. Study participants did not receive antibiotics, probiotics, prebiotics, or any other medical treatment that influences the gut microbiota during the 3 months prior to the start of the study. Intervention: Patients underwent an intervention involving a hypocaloric Mediterranean diet and a physical exercise program. The Mediterranean diet included extra virgin olive oil and nuts and reduced energy intake by approximately 600 kcal. The diet comprised fat (35–40%; 8–10% saturated fatty acids), carbohydrates (40–45%; low glycemic index), and protein (20%) (Davis et al., 2015, Nutrients 7:9139–9153; Martinez-Gonzalez and Sanchez-Villegas 2004, Eur. J. Epidemiol. 19:9–13). Dietary adherence was measured as previously described (Trichopoulou et al., 2003, N. Engl. J. Med. 348:2599–2608). Patients were encouraged to gradually increase their level of physical activity to reach at least 45 minutes per day throughout the study, which was assessed monthly by their personal trainer. Participants kept a record of their physical activity using a GENEActiv© accelerometer.Physical activity levels were assessed using the rapid physical activity assessment questionnaire (Topolski et al., 2006, Prev. Chronic Dis. 3:A118). The dietary and physical intervention involved weekly individual visits with a nutritionist for three months. In addition, a program was initiated. Nutritional education was provided to 49 participants to modify dietary and lifestyle habits with the aim of promoting both weight loss and subsequent weight maintenance. All patients fasted overnight before blood and stool collection, both before and after the intervention. The five anthropometric and clinical variables are summarized in Table 3. None of the volunteers received antibiotic, prebiotic, probiotic, synbiotic, vitamin supplement, or any other medical treatment that influences the gut microbiota during the three months prior to or during the study. Table 3. Anthropometric and analytical characteristics in cohort IV of the dietary intervention or dietary product study. Related to figure 3 (AJ). N 9 - Age (years) 45.56 ± 4.362 - Weight, kg 93.26 ± 11.83 80.12 ± 9.60 <0.001 BMI, kg / m2 36.10 ± 4.64 31 ± 3.58 <0.001 Waist (am) 115.56 ± 12.32 101.56 ± 10.23 <0.001 Hip (am) 121.11 ± 6.80 112.22 ± 6.61 <0.001 Glucose (nM) 81.78 ± 7.20 81.67 ± 7.09 0.973 Cholesterol (rrM) 193.89 ± 24.10 167.33 ± 26.87 0.006 HDL cholesterol (irM) 57.44 ± 11.57 52.22 ± 9.58 0.064 LDL cholesterol (níM) 120.58 ± 18.23 101.16 ± 22.43 0.013 Triglycerides, mg / dL 79.33 ± 29.09 69.78 ± 15.22 0.304 Insulin, pLU / ml 11.05 ± 4.64 9.12 ± 1.39 0.393 HCMA-IR 2.21 ± 0.97 1.91 ± 0.28 0.444 Hb 13.20 (12.25-14.10) 12.90 (11.90-13.85) 0.514 Hblac 5.17 ± 0.41 5.19 ± 0.28 0.834 CRP 4.75 ± 3.07 4.41 ± 2.68 0.750 INF 13.84 ± 1.03 13.88 ± 1.11 0.864 IL-6 4.33 ± 0.47 4.54 ± 1.0 0.491 Resistin 4.60 ± 1.51 5.21 ± 2.23 0.227 Adiponectin 8.63 ± 2.67 6.97 ± 3.12 0.142 Succinate (μΜ) 57.641 22.23 43.061 11.59 0.034 - 50 Data are presented as mean ± SD or median (25-75 years), as appropriate. Differences were analyzed using the paired t-test (normal distribution) or the Wilcoxon signed-rank test (non-normally distributed data). BMI: body mass index; HOMA-IR: homeostatic model assessment of insulin resistance index; SBP: systolic blood pressure; DBP: diastolic blood pressure. A p-value of less than 0.05 was considered significant. Cohort V of follow-up study Design: spontaneous observational follow-up study. Participants: Nineteen patients were followed for 2 years to assess the spontaneous progression of the gut microbiota. General counseling was provided to the subjects. None of the 19 volunteers received antibiotic, prebiotic, probiotic, synbiotic, vitamin supplement, or any other medical treatment that influences the gut microbiota in the 3 months prior to the start of the study or during the study (2 years). All patients fasted overnight before blood and stool sample collection, both before and after the follow-up period. Anthropometric and clinical variables are summarized in Table 4. Table 4. Anthropometric, clinical and microbiota characteristics of cohort V. Related to Table 5. Cohorte V n 19 Sex (muj eres / hombres) 10 / 9 Razón 2,2013,18 Succinate (μΜ) 94,22128,18 Weight (kg) 77,5 (64,8- 121,7) BMI (kg / m2) 28,5 ¢23,2-45,8) Belt (cm) 96 (83-127) Cadera (cm) 107 (101-135) TAS 128116.38 TAD 71.79110.73 Glucose (mg / dl) 92.32110.84 Cholesterol 196.32144.07 (mg / di) HDL cholesterol (mg / dl) 55.63±17.4 Triglicéridos (mg / dl) 85.26±48.12 Hblac (%) 5.59±0.54 Prevotellaceae 5.39+8.19 Veilloneaceae 1.8 (0.9-2.3) Odoribacteraceae ND Clostrídaceae 3.1 (2.8-4.8) RLQ / nn / nznz / E / Yii The data are presented as mean ± DE or median (25th-75th), as appropriate. IMG: body mass index; TAS: systolic arterial tension; TAD: diastlic arterial tension. ND: not detected. Determinaciones aníticas Blood samples were drawn after a 12-hour fast. Serum and plasma were separated and immediately frozen at -80°C. Serum biochemical parameters were measured in duplicate. Glucose, cholesterol, HDL cholesterol, and triglycerides were measured in serum using conventional enzymatic methods (Randox Laboratories Ltd., Antrim, UK). Insulin was measured using an immunoradiometric assay (BioSource International, Camarillo, CA). Gene expression analysis Total RNA was extracted from the SAT using the RNeasy Lipid Tissue Midi kit (Qiagen, Hilden, Germany). The total RNA content was measured at 260 nm, and purity was assessed using the OD260 / OD280 ratio. For gene expression analysis, 1 Fg of RNA was reverse transcribed using primers and the Reverse Transcription System (Applied Biosystems, Foster City, CA). For microRNA analysis, cDNA synthesis was performed using the TaqMan microRNA Reverse Transcription Kit (ThermoFisher Scientific, Waltham, MA). Real-time PCR (qPCR) was performed on a 7900HT Fast real-time PCR system using TaqMan gene expression assays (Applied Biosystems) for ATGL (Hs 00386101_ml), ZAG (Hs 00426651_ml), ABHD5 (Hs01104373), HSL (Hs 00193510_ml), CD163 (Hs00174705_ml), HIF1A (Hs00153153_ml), IL1B (Hs001749097_ml), and CCL2 (Hs00234140_ml). The results were calculated using - 52 the comparative Ct method (2-AACt) and were expressed in relation to the expression of the 18S maintenance gene (Hs 03928985 gl). Fecal microbiome analysis 16S sequencing (cohort II and IV) The collected stool samples were immediately frozen at -80°C. Genomic DNA was extracted following the recommendations of the International Human Microbiome Standards (IHMS; http: / / www.microbiome-standards.org) (Santiago et al., 2014, BMC Microbiol. 14:112). A frozen aliquot (250 mg) of each sample was suspended in 250 mL of guanidine thiocyanate, 40 mL of 10% N-lauroylsarcosine, and 500 mL of 5% N-lauroylsarcosine. DNA was extracted by mechanically disrupting the microbial cells with beads, and nucleic acids were recovered from the clear strands by alcohol precipitation. A 1 mg equivalent of each sample was used for DNA quantification using a spectrophotometer (NanoDrop Technologies, Wilmington, DE). DNA integrity was examined by microcapillary electrophoresis using an Agilent 2100 Bioanalyzer device with the DNA 12000 kit, which resolves the distribution of double-stranded DNA fragments up to 17.000 bp in length. Sequences of the 16S ribosomal rRNA gene were amplified from cDNA using the 16S Metagenomics kit (Thermo Fisher Scientific, Italy). The kit included two sets of primers that selectively amplify the corresponding hypervariable regions of the 16S region in bacteria: primer set V24-8 and primer set V3-6, 7-9. The PCR conditions used were 10 min at 95°C, 30 cycles of 30 s at 95°C, 30 s at 58°C, and 20 s at 72°C, followed by 10 min at 72°C. The concentration and average size of each amplicon were determined using the Quant-iT PicoGreen cDNA assay kit (Invitrogen). The number of DNA fragments per microliter was calculated, and libraries were created using the Ion Plus Fragment Library Kit (Thermo Fisher Scientific). Barcodes were added to each sample using the Ion Xpress 1-16 Barcode Adapter Kit (Thermo Fisher Scientific).Library concentrations were determined using the Ion Universal Library Quantification Kit (Thermo Fisher Scientific). Emulsion PCR and sequencing were performed. - 53 amplicon libraries on an Ion 520 chip (Ion 520™ chip kit) were sequencing using the Ion Torrent S5™ system and the Ion 520™ / 530™ Kit-Chef (Thermo Fisher Scientific) according to the manufacturer's instructions. After sequencing, individual sequence reads were filtered using Ion Reporter V4.0 software to remove low-quality and polyclonal sequences. Metagenomic analysis (cohort III and V) Total DNA was extracted from frozen human stool samples using the QIAamp DNA Stool Mini kit (Qiagen, Courtaboeuf, France). Quality assessment was performed using prinseq-lite software with the following parameters: min length, 50; trim qual right, 20; trim qual type, medium; and trim qual window, 20. R1 and R2 reads from Illumina sequencing were joined using fastq-join from the ea-tools suite. The fastq files were converted to fasta files using the fastq to fasta tool from the FastX-Toolkit. These files were then filtered against the human genome, downloaded from the NCBI FTP site (ftp: / / ftp.ncbi.nIm.nih.g0v / gen0mes / H sapiens / ).The non-aligned files, i.e., those that were not mapped against the human genome, were the input files of a BLASTn search against a custom bacterial database (Bacteria 2015 06 09) consisting of the human microbiome and bacterial genes downloaded from the NCBI FTP site (ftp: / / ftp.ncbi.nlm.nih.gov / genomes / HUMAN MICROBIOM / Bacteria / and ftp: / / ftp.ncbi.nlm.nih.gov / genomes / archive / old refseq / Bacteria / ). The best matches were extracted from the BLASTn output files, converted into contingency tables, and transformed into BIOM format for use as input files for the open-source segmentation software Quantitative Insights Into Microbial Ecology (QIIME) version 1.9.0 (Langmead and Salzberg, 2012, 9:357-359; Schmieder and Edwards, 2011, Bioinformatics 27:863-864). Measurement of circulating succinate Fluorimetric method Circulating serum / plasma succinate levels were measured -54 using the EnzyChromTM succinate assay kit (BioAssay Systems, Hayward, CA). The assay sensitivity was 12 μM and the intra- and inter-assay variance coefficients were less than 3.5 and 6.95%, respectively. CL-EM / EM and NMR analysis Circulating succinate levels obtained by the fluorimetric assay were validated using LC-MS / MS and NMR analyses. For this purpose, a subsample of plasma samples from cohort I was prepared as previously reported with some modifications (Nagana Gowda et al., 2015, Anal. Chem. 87:706-715; Tulipani et al., 2013, Anal. Chem. 85:341-348). Importantly, the succinic acid concentration measured by the fluorimetric assay correlated with that measured by LC-MS / MS (r=0.617, p=0.019) and by NMR (r=0.769, p=0.043), indicating that the fluorimetric assay could be used to measure human succinate levels, which is faster and more cost-effective than the other two methodologies. Measurement of circulating zonulin Serum zonulin was measured as a surrogate marker of intestinal permeability. Plasma / circulating serum zonulin levels were assessed using the Human Zonulin ELISA Kit (MyBiosource, San Diego, CA) (Smecuol et al., 2005, Clin. Gastroenterol. Hepatol. 3:335-341; Wang et al., 2000, J. Cell Sci. 113 Pt 24:4435-4440). This assay has high sensitivity (1 ng / ml) and excellent specificity for zonulin detection and detects only the active (uncleaved) form. Intra- and inter-assay coefficients of variation for these determinations were <10%. Statistical analysis Statistical analysis was performed using SPSS version 15 (Chicago, IL). For clinical and anthropometric variables, data with a normal distribution were expressed as mean SD, and for variables without a Gaussian distribution, they were expressed as median (25th-75th quartiles). Student's t-test with Bonferroni correction was used to compare the mean value of continuous variables with a normal distribution. -55 a Gaussian distribution, the Kruskal-Wallis test with Dunn's post-hoc multiple comparisons test was used. To analyze differences in nominal variables between groups, the χ² test was used. For microbiota data, statistical significance was tested using the independent samples t-test or the Mann-Whitney U test as part of the SPSS software package. For intervention studies, the Wilcoxon signed-rank test or the paired samples t-test was used for paired data analysis in the two prospective cohorts as appropriate. Pearson and Spearman correlation coefficients with Bonferroni adjustment were used to analyze the relationship between parameters. To determine which variables were associated with circulating succinate, multiple linear repression analysis (radual direct selection procedures) was employed.All variables associated with a succinate-containing variable in the analysis were included in their respective models. A p-value of less than 0.05 was considered significant. For functional studies, statistical analysis was performed using R statistical software version 3.3.3. The Wilcoxon rank-sum test was used for hypothesis testing between the two groups (group 1 vs. group 2). Heat maps were generated using a hierarchical clustering algorithm to visualize methanonomic function and metabolite differences within the dataset. Threshold level of succinate associated with an altered metabolic profile An altered metabolic profile in an individual is defined as a set of threshold values ​​for various parameters that are associated with the risk of developing metabolic disorders such as diabetes. The characteristic values ​​of an altered metabolic profile are as follows: Insulin > 25 pLU / ml, glucose > 100 (mg / dl), HOMA-IR > 3.21, triglycerides > 1.7 (mM). The threshold values ​​for glucose and triglycerides are values ​​defined by the American Diabetes Association, the American Heart Association, or the International Diabetes Federation to define metabolic syndrome. However, in the context of the invention, these thresholds are not -56 are necessarily related to metabolic syndrome. The threshold value for HOMA-IR (homeostatic model assessment of insulin resistance index) has been described elsewhere (Ceperuelo-Mallafré et al., J Clin Endocrinol Metab. May 2014; 99(5):E908-19; Cardona F. et al., Clin Chem. October 2006; 52(10):1920-5). Based on data from the 94 patients in cohort I (Table 1), the inventors calculated the threshold value for circulating succinate associated with an altered metabolic profile, as defined above. Specifically, the inventors used the CART (classification tree and regression) statistical method to determine the characteristic succinate values ​​of subjects with an altered metabolic profile versus subjects with an optimal one. The CART method was performed using the Statistical Package for the Social Sciences, version 19 (SPSS, Chicago, IL). The CART method is a graphical representation of a series of decision rules. CART is a nonparametric, stepwise procedure in which the classifiability of variables is evaluated with respect to a cutoff point. Subjects with values ​​less than the cutoff point are assigned to one category, while those with values ​​greater than the cutoff point are assigned to a second category in the tree.The main elements of CART are: (a) rules for splitting data at a node based on the value of a variable; (b) stopping rules for deciding when a branch is terminal and cannot be further divided; and (c) finally, a prediction for the target variable at each terminal node. The threshold value of circulating succinate obtained with this method for blood samples is 60,390 |JM (Figure 1A), while the threshold level of circulating succinate for urine samples is 10,250 |JM (Figure 1B). Example 1: Circulating succinate levels are elevated in obesity and are associated with a worse metabolic profile In a cohort of 91 patients stratified by obesity and type 2 diabetes mellitus (T2DM) (cohort 1), plasma succinate levels were significantly higher in obese individuals than in lean individuals (Figure 2A, Table 1), and a comparable increase was detected in T2DM patients with the same fat mass index (FMI), consistent with a recent report (van Diepen et al., 2017, Diabetologia 60:1304-1313). These results suggest that systemic succinate also -57 is associated with body weight status. Consequently, a positive association was found between circulating succinate levels and BMI (Figure 2B), but also with insulin, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides (Figure 2B). Consistent with the documented role of succinate in blood pressure regulation (He et al., 2004, Nature 429:188-193; Sadagopan et al., 2007, Am. J. Hypertens. 20:1209-1215), circulating succinate was also positively correlated with diastolic blood pressure (R=0.386, p=0.039). A multiple regression analysis model (R2=0.295) adjusted for age and sex showed that BMI and glucose (β=0.495 p<0.001 and β=0.279 p=0.013, respectively) were the main determinants of circulating succinate levels. Succinate has been shown to have antilipolytic actions in adipose tissue by coupling with SUCNR1, inhibiting the release of fatty acids from adipocytes (McCreath et al., 2015, Diabetes 64:1154-1167; Regard et al., 2008, Cell 135:561-571). Consistent with this, the determination of the metabolic gene expression profile in SAT from a representative subset of cohort I (n=42) revealed a negative association between systemic succinate levels and genes encoding key enzymes involved in the intracellular degradation of triacylglycerols, including adipose triglyceride lipase (ATGL), aβ-domain hydrolase containing protein 5 (ABHD5), and hormone-sensitive lipase (HSL) (Figure 2C). A similar negative association was found for the gene encoding zinc-alpha-2-glycoprotein (ZAG) of secreted lipolytic factor AT (Figure 2C).Conversely, a positive association was found between succinate and hypoxia-inducible factor HIF-Iα (Figure 2D), a key transcription factor underlying chronic inflammation and AT dysfunction in obesity (Trayhurn et al., 2008, Am. J. Physiol. Regul. Integr. Comp. Physiol. 295:R1097; Ye, 2009, Int. J. Obes. (Lond.) 33:54-66). In fact, a clear role for succinate has been established in innate immune signaling, where it enhances the production of interleukin-1 beta (IL-1β) by stabilizing HIF1α (Corcoran and O'Neill 2016, J. Clin. Invest. 126:3699-3707; Tannahill et al., 2013, Nature 496:238-242). However, systemic succinate levels were found to be associated with the expression of the marker. -58 anti-inflammatory macrophages GDI63 in SAT (Figure 2D), but not with inflammatory markers such as IL-1β or MCP-1 (R=0.116, p=0.466; R=0.039, p=0.809, respectively), supporting the idea that succinate may have differential intracellular and extracellular functions, as previously indicated for other stress-related factors such as osteopontin and heat shock proteins. It should be noted that, although some associations were also found in visceral adipose tissue, stronger correlations were detected in SAT, suggesting that subcutaneous fat depots are more sensitive to succinate than visceral fat. Example 2: The composition of the gut microbiota is associated with circulating succinate levels In an independent cohort (cohort II, clinical and anthropometric characteristics summarized in Table 2), serum succinate concentration was significantly higher in obese than non-obese individuals (43.93 ± 16.16 pM vs. 23.21 ± 1.57 pM, p = 0.0020). It should be noted that serum succinate concentration is approximately one-third lower than that found in plasma (Ariza et al., 2012, Front. Endocrinol. (Lausanne) 3:22, and this study). Analysis of the composition of the intestinal microbiota by sequencing the 16S rRNA gene revealed an increase in the Firmicutes / Bacteroidetes ratio in obese subjects (Figure 3A), and decreased richness and biodiversity at the phylum and genus level (Figure 5B-C) (Duncan et al., 2008, Int. J. Obes. (Lond.) 32:1720-1724; Ley et al., 2005, Proc. Nati. Acad. Sci. USA 102:11070-11075; Ley et al., 2006, Nature 444:1022-1023; Zhang et al., 2009, Proc. Nati. Acad. Sci. USA 106:2365-2370). It was found that the relative abundance (RA) of Prevotellaceae (37.5213.86% versus 12.9313.97%, p=0.0005) and Veillonellaceae (36.0819.52% versus 19.5114.26%, p=0.03), known succinate producers (Louis et al., 2014, Nat. Rev. Microbiol 12:661-672; Nakayama et al., 2017, Front. Microbiol. 8:197; Vogt et al., 2015, Anaerobe 34:106-115), was higher in obese than in non-obese individuals (Figure 3A). Consequently, serum succinate levels were positively correlated with Prevotellaceae (R=0.465; p=0.039). In contrast, the AR of the Odoribacteraceae (1.5810.68% vs. 6.1811.64%, p=0.005) and Clostridaceae (0.0910.04%) families was lower. - 59 versus 1.0210.36%, p=0.05), known succinate consumers (Ferreyra et al., 2014, Cell Host Microbe. 16:770-777; Reichardt et al., 2014, ISME J. 8:1323-1335), was significantly lower in obese than non-obese individuals (Figure 3A). No differences were detected in other bacterial families such as Paraprevotellaceae, Bacteroidaceae or Ruminococcaceae, which are also related to succinate metabolism (Ferreyra et al., 2014, Cell Host Microbe 16:770-777; Louis et al., 2014, Nat. Rev. Microbiol 12:661-672; Morotomi et al., 2008, Int. J. Syst. Evol. Microbiol. 58:2716-2720; O'Herrin and Kenealy 1993, Appl. Environ. Microbiol. 59:748-755; Watanabe et al., 2012, Appl. Environ. Microbiol. 78:511-518).Consequently, the ratio of [(Prevetellaceae + Veillonellaceae) / (Odoribacteraceae + Cíes tridaceae)] (r[P+V / O+C]), specific succinate producers by consumers, was significantly higher in obese subjects (Figure 3B) and was positively correlated with serum succinate levels (Figure 3C). At the genus level, the succinate-producing member Mitsuokella spp. was found to be enriched in fecal samples from obese subjects (9.67% vs. 0.11%, p=0.08), which was accompanied by a significant decrease in the succinate-consuming members Phascolarctobacterium spp. (7.27% vs. 24.15%, p=0.018) and Odoribacter spp. (0.810.27% vs. 3.6611.81%, p=0.017) (Figure 5D). Correspondingly, the gender-specific succinate-producer / succinate-consumer ratio was also significantly higher in obese than non-obese individuals (Figure 5E). According to the intestinal hyperpermeability hypothesis, the intestinal dysbiosis characteristic of obesity is directly related to the translocation of bacteria and their products into the systemic circulation (Slyepchenko et al., 2016, Curr. Pharm. Des. 22:6087-6106). As expected, circulating levels of zonulin, a useful biomarker of intestinal permeability, were significantly higher in obese than in non-obese individuals (869.331199.013 ng / ml vs. 500.87144.61 ng / ml, p=0.04). A positive correlation was found between serum succinate and circulating zonulin (R=0.61; p=0.011) (Figure 3D), which suggests that, similar to the elevated levels of circulating lipopolysaccharides in obesity, intestinal permeability may be closely associated with the presence of succinate in the systemic circulation. - 60 To further investigate the relationship between serum succinate and the gut microbiome, random sequencing of the whole genome of fecal DNA was performed in an independent cohort (confirmatory cohort III; clinical and anthropometric characteristics are summarized in Table 2). As indicated in previous cohorts, plasma succinate levels were significantly higher in obese individuals than in lean individuals (101.72±9.37 μM vs 78.24±14.4 μM, p=0.043). Furthermore, a significant increase in the Velllonellaceae family was found (2.37±0.39% vs. 1.41±0.24%, p=0.043) in obese subjects (Figure 3E), as well as a positive correlation between Velllonellaceae and plasma succinate levels (R=0.773; p<0.001) (Figure 3F). Consequently, obese subjects had a higher fam[(P+V) / (O+C)] ratio (Figure 3G), which was positively correlated with plasma succinate levels (Figure 3H).Similar to cohort II, obese individuals had higher zonulin levels (Table 2), which were also positively associated with circulating succinate levels (R=0.59; p=0.0152). An even higher fam[(P+V) / (O+C)] ratio was found for obese diabetic subjects (Figure 31). In this subgroup of patients, a correlation was found between Odoribacteriaceae and plasma succinate levels (Figure 3J). Overall, these data demonstrated that, despite interindividual heterogeneity, circulating succinate levels are associated with specific components of the gut microbiota. Interestingly, microorganisms linked to circulating succinate levels have previously been associated with cardiovascular disease (CVD) and / or its risk factors. Thus, succinate-consuming genera such as Odoribacter and Clostridium have been linked to a decrease in clinical parameters associated with CVD risk (Karlsson et al., 2012, Nat. Commun. 3:1245; Tang et al., 2017, Circ. Res. 120:1183-1196). Conversely, the genus Prevotella, which was found to be increased in obese individuals, has recently been associated with hypertension (Li et al., 2017b, Microbiome 5:14) and TMAO-induced atherosclerosis (Koet et al., 2013, Nat. Med. 19:576-585; Org et al., 2015, Atherosclerosis 241:387-399).Along these lines, Chen and colleagues have shown that resveratrol modulates the gut microbiota by inhibiting the Prevotella genus, which in turn induces a decrease in circulating TMAO levels (Chen et al., 2016, MBio 7:e02210-02215), which points to the. - 61 gut microbiota as an attractive target for pharmacological or dietary intervention or dietary products to reduce the risk of developing CVD. Example 3: Modification of the gut microbiota through dietary weight loss intervention affects circulating succinate levels To determine whether diet-induced modifications in the gut microbiota could be reflected in variations in circulating succinate levels, a prospective 12-week study of dietary intervention or dietary product was conducted in obese patients with the goal of weight loss (cohort IV, Table 3). Serum succinate levels decreased after the intervention (Figure 4A) in parallel with an increase in the richness of genera and families (Figure 6A). Although no significant differences were detected in the diversity of genera or families (Figure 6B), a decrease in the Firmicutes / Bacteroidetes ratio was identified (Figure 6C), similar to that reported in a previous dietary weight loss intervention study (Cotillard et al., 2013, Nature 500:585-588; Dao et al., 2016, Clinical Nutrition Experimental 6:39-58; Healey et al., 2017, Nutr. Rev. 75:1059-1080). According to the results of the two previous cohorts (cohorts II and III), a significant decrease was found in the succinate-producing families Prevotellaceae (17.91% vs. 7.15% vs. 2.47%, p=0.019) and Veillonellaceae (13.11% vs. 3.73% vs. 1.48%, p=0.027) after the dietary intervention or dietary product (Figure 4B). Comparatively to what was observed in cohort III, a positive correlation was found between the change in the incidence of Prevotellaceae ([Prevotellaceae] tas m intervention- [Prevotellaceae] basai) and succinate levels (R=0.751; p=0.019) (Figure 4C). Correspondingly, the fam[(P+V) / (O+C)] ratio decreased significantly after weight loss (Figure 4D) in parallel with a decrease in succinate, which was reflected in a positive correlation between the change in the fam[(P+V) / (O+C)] ratio and the change in circulating succinate (post-intervention - baseline) (Figure 4E).Similar observations were found at the gender level (Figure 6D), and the gen[(P+V) / (O+C)] ratio decreased significantly after the intervention (Figure 6E). Taken together, these results indicate that a short-term dietary weight-loss intervention impacts different members of the gut commensal community related to succinate metabolism. Specifically, a decrease in succinate producers concomitant with an increase in succinate consumers at two taxonomic levels, which correlates with the observed decrease in systemic succinate levels, points to circulating succinate as a novel metabolite associated with dysbiosis in the context of obesity. Notably, the combined analysis of both microbiota cohorts (cohorts II and IV) validated the strong positive correlation between the fam[(P+V) / (O+C)] ratio and circulating serum succinate levels (n=38, R=0.646; p<0.001). Reassuringly, multiple regression analysis revealed that the proposed ratio based on [succinate-producing] versus [succinate-consuming] families was the primary determinant of systemic succinate levels (R²=0.744, β=0.597; p=0.007). Despite these strong correlations, exactly how microbial communities interact and utilize succinate remains unknown. In addition, other microbial groups may be responsible for succinate production (e.g., Succinovibrio spp., Ruminococcus spp. or Fibrobacter succinogenes) and consumption (e.g., Dialister spp., Phascolartobacterium succinate) (Ferreyra et al., 2014, Cell Host Microbe. 16:770-777; Louis et al., 2014, Nat. Rev.Microbiol 12:661-672; Morotomi et al., 2008, Int. J. Syst. Evol. Microbiol. 58:2716-2720; O'Herrin and Kenealy 1993, Appl. Environ. Microbiol. 59:748-755; Watanabe et al., 2012, Appl. Environ. Microbiol. 78:511-518). However, the present results strongly link the specific fam[(P+V) / (O+C)] ratio with circulating succinate. Example 4: Spontaneous evolution of the microbiota drives changes in systemic succinate Finally, to assess the spontaneous evolution of the microbiota, 19 subjects were studied who received advice on general healthy habits: at baseline and 2 years later (see Methods section, description of cohort V in Table 4). No significant differences in body weight were observed in these patients. - 63 at follow-up. A metagenomic approach was used instead of 16S sequencing to analyze the gut microbiota in this cohort. At the end of follow-up, subjects were classified into two groups based on changes in the ratio of families [producing succinate] to those [consuming succinate] (group 1, decreased ratio, vs. group 2, increased ratio). A reduction in the (P+V) / (O+C) ratio was associated with a significant decrease in succinate levels (Table 5, group 1), while a significant increase in this ratio was associated with an increase in systemic succinate (Table 5, group 2). Table 5. Anthropometric and analytical characteristics in cohort V. ινΐΛ / a / zuzu / uu i oí a Follow-up study (cohort V) Group 1 Group 2 P ARatio EH-V / C+O -1,1411,29 2,8313,20 0,002 n 8 11 Sexo (women / hombres) 6 / 2 4 / 7 0, 096 ASuccinate (irM) -25,19127,11 12,33132,75 0,017 AWeight (kg) -0.25 (-19.1- 3.47) 1.8 (-1-3.8) 0.351 AIMC (kg / m2) 0.15 (-3.35- 1.42) 0.30 (-0.4-1.3) 0.840 Belt (cm) 8 (-39-11) 8 (4.75-10.5) 0.475 ACdrop (cm) 2 (-33-6) 3 (-0.5-3.75) 0.887 ATAS -0.71123.73 3.20116.56 0, 693 ATAD -1.71113.74 6.8111.50 0.185 Aglucose (mg / dl) -1±7.78 616.15 0.042 AColesterol (mg / dl) 6.12130.60 -4.09122.83 0.415 AColesterol HDL (mg / dl) 2.87112.91 0.5517.12 0.620 ATriglicéridos (mg / dl) 1.61121.61 6.63127.56 0, 675 AHblac (%) 0.4110.70 0.410.68 0.969 APzevotellaceae -3.6614.29 6.2117.68 0.005 Δ Vei 12 onel ia cea e -0.4411.89 -0.711.38 0.728 Δ Odoribacteraceae ND ND - OClostridaceae 0.26 (-0.660.44) -1.1 (-2.82- 0.58) 0.039 Data are presented as mean ± SD or median (25th–75th), as appropriate. Differences were analyzed using the t-test for independent samples (normal distribution) or the Mann-Whitney U test (data not normally distributed). Group 1 (patient ratio decreases at the end of follow-up) and group 2 (patient ratio increases at the end of follow-up); BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure. ND: not detected. A p-value of less than 0.05 was considered significant. These results demonstrate that variations in gut microbial composition, independent of changes in body weight, are directly related to circulating succinate. It should be noted that elevated systemic succinate occurred in parallel with impaired glucose homeostasis, which contrasts with recently reported findings in animal models showing that microbiota-produced succinate is directly related to improved glucose homeostasis (De Vadder et al., 2016, Cell Metab. 24:151-157). In fact, high levels of succinate have been associated with various human pathological conditions including cardiovascular disease (Aguiar et al., 2014, Cell Commun. Signal. 12:78) and T2DM (Guo et al., 2017, Nat. Commun. 8:15621; Sadagopan et al., 2007, Am. J. Hypertens. 20:1209-1215; Toma et al., 2008, J. Clin. Invest. 118:2526-2534; van Diepen et al., 2017, Diabetologia 60:13041313). Multivariate analyses identified statistically significant associations between the expression of 64 genes encoding metabolic enzymes and the fam[(P+V) / (O+C) ratio. Hierarchical clustering of these metagenomic data and associations between the fam[(P+V) / (O+C) ratio, circulating succinate, and succinate-related microbial species identified two clusters (labeled A and B, data not shown) with a clear relationship to the fam[(P+V) / (O+C) ratio, primarily reflected by succinate levels. The metagenomically derived clusters were also confirmed when analyzing associations with Prevotellaceae and Clostrida ceae, revealing a strong inverse relationship. The main positive associations in cluster A were with genes encoding metabolic enzymes involved in amino acid transport and metabolism ([E]), while cluster B -65 showed a predominance of associations with genes related to energy production and conversion ([C]). Robust relationships with genes related to carbohydrate transport and metabolism ([G]) were revealed in both clusters. Interestingly, the A1 / A2 and B1 / B2 subclusters segregated based on inverse associations with Veillonellaceae and Clostridaceae. These results link the fam[(P+V) / (O+C) ratio, the specific gut microbiota, and circulating succinate levels to a specific molecular entity and metabolic function. Differences in gene expression profiles associated with specific bacterial communities were also evident when the cohort was classified into two groups according to the fam[(P+V) / (O+C)] ratio (group 1 vs. group 2) (Figure 7). An increase in the abundance of genes encoding enzymes associated with carbohydrate transport and metabolism ([G]), such as pectate lyase [EC:4.2.2.2], pectinesterase [EC:3.1.1.11], and glycosyl hydrolase [EC:3.2.1.52], was detected after 2 years of follow-up in subjects in whom the fam[(P+V) / (O+C)] ratio increased in parallel with an increase in succinate levels. Interestingly, in these patients a decrease in the abundance of genes that encode for enzymes that connect the pentose phosphate pathway to glycolysis was also observed, such as ribulokinase [EC:2.7.1.16] and transaldolase [EC:2.2.1.2].Genes associated with metabolic pathways linked to the biosynthesis of secondary metabolites ([Q]), such as succinylbenzoic acid-CoA ligase [EC:6.2.1.26], or those associated with amino acid transport and metabolism ([E]), such as phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase [EC:5.3.1.16] and glutamate synthase [EC:1.4.1.14], were also modified. Intriguingly, all of these genes showed the strongest association with the fam [(P+V) / (O+C)] ratio (data not shown). More importantly, projecting these enzymes onto the KEGG metabolic pathway map identified central metabolism as the main process associated with the fam [(P+V) / (O+C)] ratio. Among them, glycoside hydrolase and glutamate synthase were particularly interesting due to their functional roles in activating glycolysis and producing succinate through the GABA bypass pathway.It is also worth mentioning the negative association of the fam[(P+V) / (O+C)] ratio with ribulokinase and transaldolase, which can also promote glycolysis a. -66 through inhibition of the pentose phosphate pathway (data not shown). Mapping of the main enzymes positively or negatively correlated with the fam[(P+V) / (O+C)] ratio revealed a clear connection between their functional characteristics and succinate metabolism (adapted from KEGG's metabolic pathways) (data not shown). In conclusion, the present study reveals for the first time a strong association between the microbial community, gene composition and metabolism and circulating succinate levels in humans. Example 5: Glucose tolerance test in obese mice treated with Odoribacter laneus C57 / B16 mice were fed a high-fructose diet for 16 weeks. Obese mice were then treated daily with Odoribacter laneus at 100 µL of bacteria (1109 CFU / mL) in PBS 1 with 1% glycerol (vehicle) via oral feeding through a gastric tube for 24 days. Glucose tolerance (Figure 8A) was improved in the Odoribacter laneus-treated animals. The area under the curve (AUC) is shown in Figure 8B. ινΐΛ / a / zuzu / uu i oí a

Claims

1. A kit comprising reagents suitable for determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject, wherein the kit comprises primer sets designed to hybridize specifically to the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, or wherein the kit comprises probes that hybridize specifically to the hypervariable regions of the 16S rRNA gene in at least one succinate-producing bacterium and in at least one succinate-consuming bacterium, and wherein the primer sets or probes comprise at least 10% of the total amount of reagents forming the kit.

2. Use of the kit according to claim 1, to detect the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from a subject.

3. Kit according to claim 1 or use according to claim 2, wherein the ratio of succinate-producing bacteria to succinate-consuming bacteria is the ratio of {Prevotellaceae + Veillonellaceae} / (Odoribacteriaceae + Clostridiaceae).

4. Use of a kit to determine whether the level of succinate in a sample of body fluids from a subject is above a threshold level, the kit comprising reagents suitable for determining the level of succinate in a sample of body fluids from a subject, wherein the presence of succinate in said sample of body fluids above a predetermined threshold level provides a positive result, and wherein the presence of succinate in said sample of body fluids below a predetermined threshold level or the absence of succinate in said sample of body fluids provides a negative result.

5. Use according to claim 4, wherein the subject's body fluid sample is a blood sample, a urine sample or a feces sample.

6. Use according to claim 5, wherein if the body fluid is blood the threshold level of succinate is between 50 and 70 pM, or if the body fluid is urine the threshold level of succinate is between 5 and 15 pM.

7. Use of a kit to determine whether a probiotic intervention aimed at reducing circulating succinate levels in a subject has been effective, the kit comprising reagents suitable for determining the level of succinate in a sample of body fluids from a subject, wherein a circulating succinate level in the subject's body fluid sample after the probiotic intervention lower than the circulating succinate level in the subject's body fluid sample before the probiotic intervention is indicative that the probiotic intervention has been effective, and wherein a circulating succinate level in the subject's body fluid sample after the probiotic intervention equal to or greater than the circulating succinate level in the subject's body fluid sample before the probiotic intervention is indicative that the probiotic intervention has not been effective.

8. A method for determining whether a targeted intervention, aimed at reducing circulating succinate levels in a subject, has been effective, the method comprising: (a) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject before the targeted intervention, and (b) determining the ratio of succinate-producing bacteria to succinate-consuming bacteria in a stool sample from the subject after the targeted intervention, wherein a ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject after the targeted intervention that is less than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the stool sample from the subject before the targeted intervention is indicative that the targeted intervention has been effective.and in which a ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample after the targeted intervention equal to or greater than the ratio of succinate-producing bacteria to succinate-consuming bacteria in the subject's stool sample before the targeted intervention is indicative that the targeted intervention has not been effective.

9. Method according to claim 8, wherein the targeted intervention is selected from the group consisting of a dietary intervention or dietary product, a pharmacological intervention, and a probiotic intervention.

10. Method according to any one of claims 8 or 9, wherein the patient is obese.

11. Method according to any one of claims 8-10, wherein the patient has type 2 diabetes mellitus.

12. Dietary intervention or dietary product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate in a patient, wherein the intervention decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract.

13. Dietary intervention or dietary product for use according to claim 12, wherein the intervention comprises a hypocaloric diet characterized in that: fat is 35-40% of the total daily calorie intake; and carbohydrates are 40-45% of the total daily calorie intake; wherein the dietary intervention or dietary product is administered for at least 12 weeks, and wherein the dietary intervention or dietary product is optionally administered in combination with a physical exercise program.

14. Product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate, wherein the product decreases the ratio of succinate-producing bacteria to succinate-consuming bacteria in the patient's gastrointestinal tract, wherein the product is selected from the group consisting of a pharmacological product and a probiotic product.

15. Product for use in the prevention and / or treatment of a disease associated with increased levels of circulating succinate, wherein the product decreases the patient's circulating succinate levels, wherein the product is selected from the group consisting of a pharmacological product and a probiotic product.

16. Dietary intervention or dietary product for use according to any one of claims 12 or 13, or product for use according to any one of claims 14 or 15, wherein the patient is obese.

17. Dietary intervention or dietary product for use according to any one of claims 12, 13 or 16, or product for use according to any one of claims 14-15 or 16, wherein the disease associated with increased levels of circulating succinate in a patient is selected from the group consisting of obesity, cardiovascular disease, hypertension, type 2 diabetes mellitus, chronic heart failure, ischemic heart disease, ischemia / reperfusion injury and diabetic nephropathy.

18. Dietary intervention or dietary product for use according to any one of claims 12-13 or 16-17, or product for use according to any one of claims 14 to 17, wherein the ratio of succinate-producing bacteria to succinate-consuming bacteria is the ratio of (Prevotellaceae + Veillonellaceae) / (Odoribacteriaceae + Clostridiaceae).

19. Product for use according to any one of claims 14 to 18, wherein the drug product specifically targets succinate-producing bacteria, and wherein the drug product is selected from the group consisting of an antibiotic, an antibacterial antibody, and a bacteriophage.

20. Product for use according to any one of claims 14 to 18, wherein the probiotic product comprises succinate-consuming bacteria.

21. Product for use according to claim 20, wherein the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Clostridium spp., Phascolarctobacterium spp., Ruminococcus spp. and combinations thereof.

22. Product for use according to claim 21, wherein the succinate-consuming bacteria are selected from the group consisting of Phascolarctobacterium succinatutens, Phascolarctobacterium faecium, Ruminococcus bromii and Odoribacter laneus.

23. Probiotic product comprising an effective amount of succinate-consuming bacteria, wherein the succinate-consuming bacteria are selected from the group consisting of Odoribacter spp., Phascolarctobacterium spp., Ruminococcus spp. and combinations thereof.

24. Probiotic product according to claim 23, wherein the succinate-consuming bacteria are selected from the group consisting of Phascolarctobacterium succinatutens, Phascolarctobacterium faecium, Ruminococcus bromii and Odoribacter laneus.