Veillonella and Bacteroides are associated with gestational diabetes mellitus exposure and gut microbiota immaturity.

BACKGROUND: Dysbiosis during childhood impacts the configuration and maturation of the microbiota. The immaturity of the infant microbiota is linked with the development of inflammatory, allergic, and dysmetabolic diseases. AIMS: To identify taxonomic changes associated with age and GDM and classify the maturity of the intestinal microbiota of children of mothers with GDM and children without GDM (n-GDM). METHODS: Next-generation sequencing was used to analyze the V3-V4 region of 16S rRNA gene. QIIME2 and Picrust2 were used to determine the difference in the relative abundance of bacterial genera between the study groups and to predict the functional profile of the intestinal microbiota. RESULTS: According to age, the older GDM groups showed a lower alpha diversity and different abundance of Enterobacteriaceae, Veillonella, Clostridiales, and Bacteroides. Regarding the functional profile, PWY-7377 and K05895 associated with Vitamin B12 metabolism were reduced in GDM groups. Compared to n-GDM group, GDM offspring had microbiota immaturity as age-discriminatory taxa in random forest failed to classify GDM offspring according to developmental age (OOB error 81%). Conclusion. Offspring from mothers with GDM have a distinctive taxonomic profile related to taxa associated with gut microbiota immaturity.

Advances in extracellular vesicles as mediators of cell-to-cell communication in pregnancy.

Cell-to-cell communication mediated by Extracellular Vesicles (EVs) is a novel and emerging area of research, especially during pregnancy, in which placenta derived EVs can facilitate the feto-maternal communication. EVs comprise a heterogeneous group of vesicle sub-populations with diverse physical and biochemical characteristics and originate by specific biogenesis mechanisms. EVs transfer molecular cargo (including proteins, nucleic acids, and lipids) between cells and are critical mediators of cell communication. There is growing interest among researchers to explore into the molecular cargo of EVs and their functions in a physiological and pathological context. For example, inflammatory mediators such as cytokines are shown to be released in EVs and EVs derived from immune cells play key roles in mediating the immune response as well as immunoregulatory pathways. Pregnancy complications such as gestational diabetes mellitus, preeclampsia, intrauterine growth restriction and preterm birth are associated with altered levels of circulating EVs, with differential EV cargo and bioactivity in target cells. This implicates the intriguing roles of EVs in reprogramming the maternal physiology during pregnancy. Moreover, the capacity of EVs to carry bioactive molecules makes them a promising tool for biomarker development and targeted therapies in pregnancy complications. This review summarizes the physiological and pathological roles played by EVs in pregnancy and pregnancy-related disorders and describes the potential of EVs to be translated into clinical applications in the diagnosis and treatment of pregnancy complications.

Early-Pregnancy Serum Maternal and Placenta-Derived Exosomes miRNAs Vary Based on Pancreatic ß-Cell Function in GDM.

CONTEXT: Pancreatic ß-cell function impairment is a key mechanism for developing gestational diabetes mellitus (GDM). Maternal and placental exosomes regulate maternal and placental responses during hyperglycemia. Studies have associated exosomal micro-RNAs (miRNAs) with GDM development. To date, no studies have been reported that evaluate the profile of miRNAs present in maternal and placental exosomes in the early stages of gestation from pregnancies that develop GDM. OBJECTIVE: We assessed whether early-pregnancy serum maternal and placenta-derived exosomes miRNA profiles vary according to pancreatic ß-cell function in women who will develop GDM. METHODS: A prospective nested case-control study was used to identify exosomal miRNAs that vary in early-pregnancy stages (<18 weeks of gestation) from women with normoglycemia and those who developed GDM based on their pancreatic ß-cell function using the homeostasis model assessment of pancreatic ß-cell function (HOMA-%ß) index. Early-pregnancy serum maternal and placenta-derived exosomes were isolated to obtain miRNA profiles. Potential target and pathway analyses were performed to identify molecular and metabolic pathways associated with the exosomal miRNAs identified. RESULTS: In early-pregnancy stages, serum maternal exosome size and concentration are modified in GDM group and fluctuate according to HOMA-%ß index. Serum maternal exosomal hsa-miR-149-3p and hsa-miR-455-3p in GDM are related to insulin secretion and signaling, lipolysis, and adipocytokine signaling. Early-pregnancy serum placenta-derived exosomes hsa-miR-3665 and hsa-miR-6727-5p in GDM are related to regulating genes involved in response to immunological tolerance of pregnancy and pathways associated with placental dysfunction. CONCLUSION: Early serum exosomal miRNAs differ depending on their origin (maternal or placental) and pancreatic ß-cell function. This research provides insights into the interactions between maternal and placental exosomal miRNAs and may have implications for identifying potential biomarkers or therapeutic targets for GDM.

Dietary Patterns Are Associated with the Gut Microbiome and Metabolic Syndrome in Mexican Postmenopausal Women.

Postmenopausal women are at an increased risk of developing metabolic syndrome (MetS) due to hormonal changes and lifestyle factors. Gut microbiota (GM) have been linked to the development of MetS, and they are influenced by dietary habits. However, the interactions between dietary patterns (DP) and the GM of postmenopausal women, as well as their influence on MetS, still need to be understood. The present study evaluated the DP and microbiota composition of postmenopausal Mexican women with MetS and those in a control group. Diet was assessed using a food frequency questionnaire, and the GM were profiled using 16S rRNA gene sequencing. Greater adherence to a "healthy" DP was significantly associated with lower values of MetS risk factors. GM diversity was diminished in women with MetS, and it was negatively influenced by an "unhealthy" DP. Moreover, a higher intake of fats and proteins, as well as lower amounts of carbohydrates, showed a reduction in some of the short-chain fatty acid-producing genera in women with MetS, as well as increases in some harmful bacteria. Furthermore, Roseburia abundance was positively associated with dietary fat and waist circumference, which may explain 7.5% of the relationship between this macronutrient and MetS risk factors. These findings suggest that GM and diet interactions are important in the development of MetS in postmenopausal Mexican women.

Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity.

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.

Machine learning accurately predicts food exchange list and the exchangeable portion.

Introduction: Food Exchange Lists (FELs) are a user-friendly tool developed to help individuals aid healthy eating habits and follow a specific diet plan. Given the rapidly increasing number of new products or access to new foods, one of the biggest challenges for FELs is being outdated. Supervised machine learning algorithms could be a tool that facilitates this process and allows for updated FELs-the present study aimed to generate an algorithm to predict food classification and calculate the equivalent portion. Methods: Data mining techniques were used to generate the algorithm, which consists of processing and analyzing the information to find patterns, trends, or repetitive rules that explain the behavior of the data in a food database after performing this task. It was decided to approach the problem from a vector formulation (through 9 nutrient dimensions) that led to proposals for classifiers such as Spherical K-Means (SKM), and by developing this idea, it was possible to smooth the limits of the classifier with the help of a Multilayer Perceptron (MLP) which were compared with two other algorithms of machine learning, these being Random Forest and XGBoost. Results: The algorithm proposed in this study could classify and calculate the equivalent portion of a single or a list of foods. The algorithm allows the categorization of more than one thousand foods with a confidence level of 97% at the first three places. Also, the algorithm indicates which foods exceed the limits established in sodium, sugar, and/or fat content and show their equivalents. Discussion: Accurate and robust FELs could improve implementation and adherence to the recommended diet. Compared with manual categorization and calculation, machine learning approaches have several advantages. Machine learning reduces the time needed for manual food categorization and equivalent portion calculation of many food products. Since it is possible to access food composition databases of various populations, our algorithm could be adapted and applied in other databases, offering an even greater diversity of regional products and foods. In conclusion, machine learning is a promising method for automation in generating FELs. This study provides evidence of a large-scale, accurate real-time processing algorithm that can be useful for designing meal plans tailored to the foods consumed by the population. Our model allowed us not only to distinguish and classify foods within a group or subgroup but also to perform the calculation of an equivalent food. As a neural network, this model could be trained with other food bases and thus improve its predictive capacity. Although the performance of the SKM model was lower compared to other types of classifiers, our model allows selecting an equivalent food not from a group previously classified by machine learning but with a fully interpretable algorithm such as cosine similarity for comparing food.

An early prediction model for gestational diabetes mellitus based on metabolomic biomarkers.

BACKGROUND: Gestational diabetes mellitus (GDM) represents the main metabolic alteration during pregnancy. The available methods for diagnosing GDM identify women when the disease is established, and pancreatic beta-cell insufficiency has occurred.The present study aimed to generate an early prediction model (under 18 weeks of gestation) to identify those women who will later be diagnosed with GDM. METHODS: A cohort of 75 pregnant women was followed during gestation, of which 62 underwent normal term pregnancy and 13 were diagnosed with GDM. Targeted metabolomics was used to select serum biomarkers with predictive power to identify women who will later be diagnosed with GDM. RESULTS: Candidate metabolites were selected to generate an early identification model employing a criterion used when performing Random Forest decision tree analysis. A model composed of two short-chain acylcarnitines was generated: isovalerylcarnitine (C5) and tiglylcarnitine (C5:1). An analysis by ROC curves was performed to determine the classification performance of the acylcarnitines identified in the study, obtaining an area under the curve (AUC) of 0.934 (0.873-0.995, 95% CI). The model correctly classified all cases with GDM, while it misclassified ten controls as in the GDM group. An analysis was also carried out to establish the concentrations of the acylcarnitines for the identification of the GDM group, obtaining concentrations of C5 in a range of 0.015-0.25 µmol/L and of C5:1 with a range of 0.015-0.19 µmol/L. CONCLUSION: Early pregnancy maternal metabolites can be used to screen and identify pregnant women who will later develop GDM. Regardless of their gestational body mass index, lipid metabolism is impaired even in the early stages of pregnancy in women who develop GDM.

Pecans and Its Polyphenols Prevent Obesity, Hepatic Steatosis and Diabetes by Reducing Dysbiosis, Inflammation, and Increasing Energy Expenditure in Mice Fed a High-Fat Diet.

Pecans (Carya illinoinensis) are considered a functional food due to the high content of polyunsaturated fatty acids, dietary fiber and polyphenols. To determine the effect of whole pecans (WP) or a pecan polyphenol (PP) extract on the development of metabolic abnormalities in mice fed a high-fat (HF) diet, we fed C57BL/6 mice with a Control diet (7% fat), HF diet (23% fat), HF containing 30% WP or an HF diet supplemented with 3.6 or 6 mg/g of PP for 18 weeks. Supplementation of an HF diet with WP or PP reduced fat mass, serum cholesterol, insulin and HOMA-IR by 44, 40, 74 and 91%, respectively, compared to the HF diet. They also enhanced glucose tolerance by 37%, prevented pancreatic islet hypertrophy, and increased oxygen consumption by 27% compared to the HF diet. These beneficial effects were associated with increased thermogenic activity in brown adipose tissue, mitochondrial activity and AMPK activation in skeletal muscle, reduced hypertrophy and macrophage infiltration of subcutaneous and visceral adipocytes, reduced hepatic lipid content and enhanced metabolic signaling. Moreover, the microbial diversity of mice fed WP or PP was higher than those fed HF, and associated with lower circulating lipopolysaccharides (~83-95%). Additionally, a 4-week intervention study with the HF 6PP diet reduced the metabolic abnormalities of obese mice. The present study demonstrates that WP or a PP extract prevented obesity, liver steatosis and diabetes by reducing dysbiosis, inflammation, and increasing mitochondrial content and energy expenditure. Pecan polyphenols were mainly condensed tannin and ellagic acid derivatives including ellagitannins as determined by LC-MS. Herein we also propose a model for the progression of the HF diet-mediated metabolic disorder based on early and late events, and the possible molecular targets of WP and PP extract in preventive and intervention strategies. The body surface area normalization equation gave a conversion equivalent to a daily human intake dose of 2101-3502 mg phenolics that can be obtained from 110-183 g pecan kernels/day (22-38 whole pecans) or 21.6-36 g defatted pecan flour/day for an average person of 60 kg. This work lays the groundwork for future clinical studies.

Micro- and Macronutrient Intake and Food Group Frequency Consumed by Subjects with Cognitive Impairment and Dementia in Latin America: A Systematic Review.

BACKGROUND: Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and cognitive dysfunction have. OBJECTIVE: The main purpose of this study was to determine micro- and macronutrients and food frequency intake among the LAC population with mild cognitive impairment (MCI) and dementia. METHODS: A systematic review using PubMed, Cochrane, Lilacs, and Scielo databases. Energy intake as well as micro- and macronutrients intake were analyzed using a random-effect model and presented in a forest plot. RESULTS: Nine articles were included, an estimated energy intake of 1598.47 kcal (95% CI 1351.07-1845.88) was obtained. A daily consumption of 73.64 g/day (95% CI 64.07-83.2) of protein; 262.17 g/day (95% CI 214.51-309.93) of carbohydrates, and 57.91 g/day (95% CI 49.16-66.66) of fats were reported. A micronutrients daily intake consumption of 201.35µg/day of vitamin B9 (95% CI 125.32-277.38); 5.61µg/day of vitamin B12 (95% CI 2.53-8.70), and 139.67 mg/day of vitamin C (95% CI 59.33-220.02). Mineral intake of 637.32 mg/day of calcium (95% CI 288.54-986.11) and 9 mg/day of iron (95% CI 2.28-15.71) was obtained. A low intake of fruits and vegetables was found. CONCLUSION: Individuals with MCI and dementia from LAC have a nutritional deficiency characterized by a lower intake of fruits and vegetables, a high consumption of carbohydrates and protein, adequate fats intake and vitamins B12, vitamin C, and iron consumption, but a low intake of vitamin B9 and calcium.

Vachellia farnesiana Pods or a Polyphenolic Extract Derived from Them Exert Immunomodulatory, Metabolic, Renoprotective, and Prebiotic Effects in Mice Fed a High-Fat Diet.

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.

Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex.

BACKGROUND: M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related changes in the transcriptome of M1 macrophages during the internalization process of LDL particles. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy male and female subjects were separated using Hystopaque, and monocytes were isolated from PBMCs using a positive selection of CD14+ cells. Cells were stimulated with LDL 10 µg/mL, and the transcriptional profile of M1 macrophages performed during LDL internalization was determined using a Clariom D platform array. RESULTS: Chromosome Y influences the immune system and inflammatory responses in males expressing 43% of transcripts in response to LDL treatment. Males and females share 15 transcripts, where most correspond to non-coding elements involved in oxidative stress and endothelial damage. CONCLUSIONS: During LDL internalization, male monocyte-derived M1 macrophages display more marked proinflammatory gene expression. In contrast, female M1 macrophages display a more significant number of markers associated with cell damage.

The impact of short-chain fatty acid-producing bacteria of the gut microbiota in hyperuricemia and gout diagnosis.

INTRODUCTION/OBJECTIVES: Persistent hyperuricemia is a key factor in gout; however, only 13.5% of hyperuricemic individuals manifest the disease. The gut microbiota could be one of the many factors underlying this phenomenon. We aimed to assess the difference in taxonomic and predicted functional profiles of the gut microbiota between asymptomatic hyperuricemia (AH) individuals and gout patients. METHODS: The V3-V4 region of the 16S rRNA gene of the gut microbiota of AH individuals, gout patients, and controls was sequenced. Bioinformatic analyses were carried out with QIIME2 and phyloseq to determine the difference in the relative abundance of bacterial genera among the study groups. Tax4fun2 was used to predict the functional profile of the gut microbiota. RESULTS: AH individuals presented a higher abundance of butyrate- and propionate-producing bacteria than gout patients; however, the latter had more bacteria capable of producing acetate. The abundance of Prevotella genus bacteria was not significantly different between the patients but was higher than that in controls. This result was corroborated by the functional profile, in which AH individuals had less pyruvate oxidase abundance than gout patients and less abundance of an enzyme that regulates glutamate synthetase activation than controls. CONCLUSION: We observed a distinctive taxonomic profile in AH individuals characterized by a higher abundance of short-chain fatty acid-producing bacteria in comparison to those observed in gout patients. Furthermore, we provide scientific evidence that indicates that the gut microbiota of AH individuals could provide anti-inflammatory mediators, which prevent the appearance of gout flares. Key Points • AH and gout patients both have a higher abundance of Prevotella genus bacteria than controls. • AH individuals' gut microbiota had more butyrate- and propionate-producing bacteria than gout patients. • The gut microbiome of AH individuals provides anti-inflammatory mediators that could prevent gout flares.

Targeted Metabolomics Revealed a Sex-Dependent Signature for Metabolic Syndrome in the Mexican Population.

Metabolic syndrome (MetS) is a group of several metabolic conditions predisposing to chronic diseases. Individuals diagnosed with MetS are physiologically heterogeneous, with significant sex-specific differences. Therefore, we aimed to investigate the potential sex-specific serum modifications of amino acids and acylcarnitines (ACs) and their relationship with MetS in the Mexican population. This study included 602 participants from the Health Workers Cohort Study. Forty serum metabolites were analyzed using a targeted metabolomics approach. Multivariate regression models were used to test associations of clinical and biochemical parameters with metabolomic profiles. Our findings showed a serum amino acid signature (citrulline and glycine) and medium-chain ACs (AC14:1, AC10, and AC18:10H) associated with MetS. Glycine and AC10 were specific metabolites representative of discrimination according to sex-dependent MetS. In addition, we found that glycine and short-chain ACs (AC2, AC3, and AC8:1) are associated with age-dependent MetS. We also reported a significant correlation between body fat and metabolites associated with sex-age-dependent MetS. In conclusion, the metabolic profile varies by MetS status, and these differences are sex-age-dependent in the Mexican population.

Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance.

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.

Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.

BACKGROUND AND AIM: Circulating amino acids are modified by sex, body mass index (BMI) and insulin resistance (IR). However, whether the presence of genetic variants in branched-chain amino acid (BCAA) catabolic enzymes modifies circulating amino acids is still unknown. Thus, we determined the frequency of two genetic variants, one in the branched-chain aminotransferase 2 (BCAT2) gene (rs11548193), and one in the branched-chain ketoacid dehydrogenase (BCKDH) gene (rs45500792), and elucidated their impact on circulating amino acid levels together with clinical, anthropometric and biochemical parameters. METHODS AND RESULTS: We performed a cross-sectional comparative study in which we recruited 1612 young adults (749 women and 863 men) aged 19.7 ± 2.1 years and with a BMI of 24.9 ± 4.7 kg/m2. Participants underwent clinical evaluation and provided blood samples for DNA extraction and biochemical analysis. The single nucleotide polymorphisms (SNPs) were determined by allelic discrimination using real-time polymerase chain reaction (PCR). The frequencies of the less common alleles were 15.2 % for BCAT2 and 9.83 % for BCKDH. The subjects with either the BCAT2 or BCKDH SNPs displayed no differences in the evaluated parameters compared with subjects homozygotes for the most common allele at each SNP. However, subjects with both SNPs had higher body weight, BMI, blood pressure, glucose, and circulating levels of aspartate, isoleucine, methionine, and proline than the subjects homozygotes for the most common allele (P < 0.05, One-way ANOVA). CONCLUSION: Our findings suggest that the joint presence of both the BCAT2 rs11548193 and BCKDH rs45500792 SNPs induces metabolic alterations that are not observed in subjects without either SNP.

Serum Metabolite Profile Associated with Sex-Dependent Visceral Adiposity Index and Low Bone Mineral Density in a Mexican Population.

Recent evidence shows that obesity correlates negatively with bone mass. However, traditional anthropometric measures such as body mass index could not discriminate visceral adipose tissue from subcutaneous adipose tissue. The visceral adiposity index (VAI) is a reliable sex-specified indicator of visceral adipose distribution and function. Thus, we aimed to identify metabolomic profiles associated with VAI and low bone mineral density (BMD). A total of 602 individuals from the Health Workers Cohort Study were included. Forty serum metabolites were measured using the targeted metabolomics approach, and multivariate regression models were used to test associations of metabolomic profiles with anthropometric, clinical, and biochemical parameters. The analysis showed a serum amino acid signature composed of glycine, leucine, arginine, valine, and acylcarnitines associated with high VAI and low BMD. In addition, we found a sex-dependent VAI in pathways related to primary bile acid biosynthesis, branched-chain amino acids, and the biosynthesis of pantothenate and coenzyme A (CoA). In conclusion, a metabolic profile differs by VAI and BMD status, and these changes are gender-dependent.

Altered Microbial Composition of Drug-Sensitive and Drug-Resistant TB Patients Compared with Healthy Volunteers.

Mycobacterium tuberculosis infection has three discernible outcomes: active tuberculosis, latent tuberculosis, or clearance of the bacterium. The outcome of the infection depends on the interaction of the bacterium, the immune system, and the microbiome of the host. The current study uses 16S rRNA sequencing to determine the diversity and composition of the respiratory microbiome of drug-resistant and drug-sensitive tuberculosis patients as well as healthy volunteers. Tuberculosis patients exhibited increased microbial diversity and differentially abundant bacteria than healthy volunteers. Compositional differences were also observed when comparing drug-sensitive or -resistant tuberculosis patients. Finally, we defined and assessed the differences in the core sputum microbiota between tuberculosis patients and healthy volunteers. Our observations collectively suggest that in sputum, Mycobacterium tuberculosis infection is related to altered bacterial diversity and compositional differences of core members of the microbiome, with potential implications for the bacterial pulmonary ecosystem's stability and function.

Gut Microbiota in Mexican Children With Acute Diarrhea: An Observational Study.

BACKGROUND: Acute diarrhea is the second leading cause of preventable mortality and morbidity in children worldwide. This study aimed to identify the main pathogens associated with acute diarrhea and to describe changes in gut microbiota in Mexican children. METHODS: This single-center observational study included 30 children (6 months to 5 years old) with acute diarrhea who were referred to the Instituto Nacional de Pediatría of Mexico City and 15 healthy volunteers (control group). Stool samples at day 0 (D0) and day 15 (D15) were collected for identification of microorganisms (reverse transcriptase-polymerase chain reaction analyses with xTAG gastrointestinal pathogen panel multiplex assay) and microbiota analysis (16S gene amplification sequencing). Prescription decisions were made by the treating clinician. RESULTS: The main pathogens identified were norovirus and Campylobacter jejuni (20% each). The majority of patients (n = 24) were prescribed Saccharomyces boulardii CNCM I-745 for treatment of acute diarrhea. Diarrheic episodes resolved within 1 week of treatment. Compared with D15 and control samples, D0 samples showed significantly lower alpha diversity and a clear shift in overall composition (beta diversity). Alpha diversity was significantly increased in S. boulardii-treated group between D0 and D15 to a level similar to that of control group. CONCLUSIONS: In these children, acute diarrhea was accompanied by significant alterations in gut microbiota. S. boulardii CNCM I-745 treatment may facilitate gut microbiota restoration in children with acute diarrhea, mostly through improvements in alpha diversity.

Metabolic flexibility during normal pregnancy allows appropriate adaptation during gestation independently of BMI.

BACKGROUND & AIMS: Overweight and obesity in reproductive-age women hasten the development of insulin resistance and increase risk for deterioration of pregnancy metabolism. These pregnancy-associated metabolic changes are similar to those of the metabolic syndrome. Thus, some metabolic flexibility must allow appropriate adaptation to the metabolic load that pregnancy imposes. We evaluated metabolic flexibility during uncomplicated pregnancy in women with pre-gestational normal weight or overweight. METHODS: In 20 women with singleton pregnancies, pre-pregnancy BMI was categorized as normal-weight (Nw) or overweight (Ow). The women were seen quarterly, and fasting and postprandial blood samples were collected at each visit. Indirect fasting and/postprandial calorimetry was performed to evaluate metabolic flexibility (Δrespiratory quotient (RQ) = RQpostprandial - RQfasting). RESULTS: In the first trimester, metabolic flexibility was lower in the Ow group compared to the Nw group (0.031 ± 0.0131 vs 0.077 ± 0.018, respectively) without a statistically significant difference (p = 0.053). In the second trimester, the Ow group was significantly more flexible than the Nw group (0.190 ± 0.016 vs 0.077 ± 0.015, respectively (p = 0.004)). For the third trimester, the Ow and Nw groups did not differ in metabolic flexibility (0.074 ± 0.013 vs 0.087 ± 0.021, respectively) (p = 0.40). The most influential variables for metabolic flexibility during pregnancy were lactate, leptin, ß-hydroxybutyrate, glycerol, aromatic amino acids, medium and long chain acylcarnitine's. CONCLUSIONS: Our findings indicate that metabolic flexibility changes throughout pregnancy, independently of pre-pregnancy BMI. These changes maintain metabolic homeostasis between the mother and foetus, allowing for appropriate adjustments during pregnancy.

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

OBJECTIVE: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. METHODS: Hypervariable V3-V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. RESULTS: We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. CONCLUSION: Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.