Metabolomics of the diabetic nephropathy: behind the fingerprint of development and progression indicators. / Metabolómica de la nefropatía diabética: tras la huella de indicadores de desarrollo y progresión.

Current diagnostic methods are not very sensitive to detect the initial stages diabetic nephropathy of type 2. In this work, a review of metabolomic approximation studies for the identification of biomarkers of this disease with potential to differentiate between early stages, evaluate and direct treatment and help slow kidney damage. Using public (Pubmed and Google Scholar) and private (Scopus and Web of Knowledge) databases, a systematic search of the information published related to metabolomics of diabetic nephropathy in different biospecimens (urine, serum, plasma and blood) was made. Later, the MetaboAnalyst 4.0 software was used to identify the metabolic pathways associated with these metabolites. Groups of potential metabolites were identified for monitoring diabetic nephropathy with the available literature data. In the urine, oxide-3-hydroxyisovalerate, TMAO, aconite and citrate and hydroxypropionate derivatives are highlighted; meanwhile, in the serum: citrate, creatinine, arginine and its derivatives; and in the plasma: amino acids such as histidine, methionine and arginine has a potential contribution. Using MetaboAnalyst 4.0 the metabolic pathways related to these metabolites were related. The search for biomarkers to measure the progression of diabetic nephropathy, together with analytical strategies for their detection and quantification, are the starting point for designing new methods of clinical chemistry analysis. The association between the metabolic pathway dysfunction could be useful for the overall assessment of the treatment and clinical follow-up of this disease.

Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery.

OBJECTIVE: Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development. DESIGN: A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed. RESULTS: Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight. CONCLUSION: Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.