Evaluation of gut microbiota predictive potential associated with phenotypic characteristics to identify multifactorial diseases.

Gut microbiota has been implicated in various clinical conditions, yet the substantial heterogeneity in gut microbiota research results necessitates a more sophisticated approach than merely identifying statistically different microbial taxa between healthy and unhealthy individuals. Our study seeks to not only select microbial taxa but also explore their synergy with phenotypic host variables to develop novel predictive models for specific clinical conditions. DESIGN: We assessed 50 healthy and 152 unhealthy individuals for phenotypic variables (PV) and gut microbiota (GM) composition by 16S rRNA gene sequencing. The entire modeling process was conducted in the R environment using the Random Forest algorithm. Model performance was assessed through ROC curve construction. RESULTS: We evaluated 52 bacterial taxa and pre-selected PV (p < 0.05) for their contribution to the final models. Across all diseases, the models achieved their best performance when GM and PV data were integrated. Notably, the integrated predictive models demonstrated exceptional performance for rheumatoid arthritis (AUC = 88.03%), type 2 diabetes (AUC = 96.96%), systemic lupus erythematosus (AUC = 98.4%), and type 1 diabetes (AUC = 86.19%). CONCLUSION: Our findings underscore that the selection of bacterial taxa based solely on differences in relative abundance between groups is insufficient to serve as clinical markers. Machine learning techniques are essential for mitigating the considerable variability observed within gut microbiota. In our study, the use of microbial taxa alone exhibited limited predictive power for health outcomes, while the integration of phenotypic variables into predictive models substantially enhanced their predictive capabilities.

What is Already Known on this Subject? While the gut microbiota has been implicated as potential signatures or biomarkers for various clinical conditions, the establishment of causality in humans remains largely elusive.The role of the gut microbiota in maintaining the host organism's proper physiological function is well-established, yet data regarding the composition of the gut microbiota in disease states often suffer from poor reproducibility.What Are the New Findings? Our study demonstrates that relying solely on differences in the relative abundance of bacterial taxa between groups falls short as a means of identifying clinical markers.We advocate the use of robust statistical tools, such as bootstrapping, to mitigate the substantial variability observed in gut microbiota studies, thereby enhancing the reproducibility of research findings.Our findings underscore the limited predictive power of microbial taxa in isolation for health outcomes.The integration of phenotypic variables into predictive models with gut microbiota significantly augments the ability to predict health outcomes.How This Study Might Advance Research Despite the growing enthusiasm for using gut microbiota as biomarkers for various clinical conditions, the lack of standardization throughout the research process impedes progress in this field.Our study emphasizes the necessity of rigorously testing predictions of clinical conditions based on gut microbiota using bootstrapping techniques, promoting greater reproducibility in research findings.

Is There an Advantage in Enriching Parenteral Lipid Emulsions Containing Fatty Acids From Fish Oil With Medium-Chain Triglycerides? A Study on Body Pool Concentrations of ω-3 Fatty Acids in Lewis Rats.

BACKGROUND: The addition of medium-chain triglycerides (MCTs) into parenteral lipid emulsions rich in fatty acids from fish oil (FOLEs) has been shown to improve their clearance and extrahepatic uptake. We assessed whether this effect could favor the leukocyte uptake of ω-3 polyunsaturated fatty acids (PUFAs) for immunomodulatory purposes METHODS: Following 5-day adaptation in metabolic cages, 42 male Lewis rats fed with AIN-93M chow were killed (baseline control group [BC]) or submitted to central venous catheterization and distributed into (1) surgical control group without parenteral infusion (chow group), (2) test emulsion (MCT/LCT/FO) group with the parenteral infusion of a FOLE containing 40% MCT, and (3) control emulsion group (LCT/FO) with the parenteral infusion of an FOLE without MCT. The 2 FOLEs had similar ω-3 PUFA contents and ω-6/ω-3 PUFA ratios and were infused during 48 and 72 hours. Concentrations of ω-3 and ω-6 PUFAs in plasma, liver, and blood mononuclear and polymorphonuclear leukocytes were assessed by gas chromatography RESULTS: In both FOLE groups, leukocyte concentrations of ω-3 PUFAs peaked after 48 hours' infusion (vs BC). At this time point, plasma concentrations of ω-3 PUFAs were higher in MCT/LCT/FO group than in LCT/FO group and the opposite was found in the liver (P<.05), but no differences in PUFA concentrations were observed between these groups in leukocytes (P>.05) CONCLUSION: The ω-3 PUFAs provided by FOLEs rich in MCT were less incorporated by liver and remained more available for extrahepatic cell delivery, but this did not result in a clear benefit in increasing their incorporation by peripheral leukocytes.

Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include a Compensatory Mechanism That Balances Fatty Acid ß and ω Oxidation.

BACKGROUND: More than half of patients who undergo Roux-en-Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal (GI) metabolic mechanisms of this improvement are still elusive. METHODS: Paired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18), and ileum (n = 18), collected by double-balloon enteroscopy. RESULTS: After RYGB, improvements in body composition and weight-related and glucose homeostasis parameters were observed. Plasma-enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid (TCA) cycles, gluconeogenesis, malate-aspartate shuttle, and carnitine synthesis. In GI tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the TCA cycle were enriched, particularly in plasma, jejunum, and ileum. Fluctuations of dicarboxylic acids (DCAs) were relevant in several metabolomic tests, and metabolite alterations included aminomalonate and fumaric, malic, oxalic, and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism. CONCLUSIONS: RYGB was associated with systemic and GI metabolic reprogramming. DCA alterations link ω and ß fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement.

NUTRITIONAL SUPPORT FOR FULMINANT HEPATITIS.

INTRODUCTION: fulminant hepatitis (FH) is associated with exacerbated hypercatabolism, hypoglycemia and hyperammonemia that are accompanied by the release of proinflammatory cytokines and catabolic hormones into the systemic circulation worsening patient's clinical condition. Nutritional support is a crucial element for the recovery of these patients. OBJECTIVES: the aim of this review is to update Nutritional Support for Fulminant Hepatitis. METHODS: the review was performed using electronic search on Medline-PubMed using Mesh-terms. RESULTS AND DISCUSSION: there are not many data available on nutritional support to fulminant hepatitis or acute liver failure. Strategies for initial nutritional intervention are focused on the control of the previously described FH metabolic derangements, and should be individualized according to the severity of patient's clinical condition. Energy and protein can be provided in amounts of 25­40 kcal/kg/day and 0.8-1.2 g/kg/day, respectively. Enteral nutrition therapy is indicated for patients with advancing encephalopathy or for those who cannot be properly fed orally. Euglycemia must be achieved and protein intake can be based on BCAA formulae. Lipids can be administered as energy supplementation with caution. Adequate nutrition therapy can potentially reduce morbidity and mortality of FH patients.

Introducción: la hepatitis fulminante se asocia a un exacerbado hipercatabolismo, la hipoglicemia y la hiperamonemia están acompañadas por la liberación de citocinas proinflamatorias y hormonas catabólicas en la circulación sistémica, empeorando la condición clínica del paciente. El apoyo nutricional es un elemento crucial para la recuperación de estos pacientes. Objetivos: el objetivo de esta revisión es actualizar el apoyo nutricional para la hepatitis fulminante. Métodos: la revisión se llevó a cabo mediante la búsqueda electrónica en Medline-PubMed, utilizando malla de términos. Resultados y discusión: no hay muchos datos disponibles sobre el apoyo nutricional para lahepatitis fulminante o fallo hepático agudo. Las estrategias de intervención nutricional inicial se centran en el control de los trastornos metabólicos de la hepatitis fulminante descritos anteriormente, que deben ser individualizadas de acuerdo a la gravedad de la situación clínica del paciente. Energía y proteína se pueden proporcionar en cantidades de 25­40 kcal / kg / día y 0,8-1,2 g / kg / día, respectivamente. La terapia nutricional enteral está indicada en pacientes con encefalopatía avanzada o para aquellos que no pueden ser adecuadamente alimentados por vía oral. Se debe obtener una euglicemia y la ingesta de proteínas puede estar basada en fórmulas de BCAA. Los lípidos se pueden administrar como suplemento energético con precaución. Una terapia nutricional adecuada puede potencialmente reducir la morbilidad y la mortalidad de los pacientes con hepatitis fulminante.

Ingestion of glutamine and maltodextrin two hours preoperatively improves insulin sensitivity after surgery: a randomized, double blind, controlled trial.

OBJECTIVE: To investigate whether the abbreviation of preoperative fasting with a drink containing glutamine and dextrinomaltose improves organic response to surgical trauma. METHODS: Thirty-six female patients adult (18-62 years) candidates for elective laparoscopic cholecystectomy were randomly divided into three groups: conventional fasting (fasting group), and two groups receiving two different diets, eight hours (400ml) and two hours before induction of anesthesia (200ml): carbohydrate (CHO) group (12.5% dextrinomaltose) and the glutamine (GLN) group (12.5% dextrinomaltose and 40 and 10g of glutamine, respectively). Blood samples were collected pre and postoperatively. RESULTS: Twenty-eight patients completed the study. No pulmonary complication occurred. Gastric residual volume was similar between groups (p = 0.95). Postoperatively, all patients from the fasting group had abnormal glucose (> 110mg/dl), this abnormality being of 50% when compared to the CHO group (p = 0.14), and of 22.2% when compared to the GLN group (p = 0.01). All patients who had the fasting period shortened (CHO + GLN) had normal postoperative insulin, contrasting with 66.7% in the fasted group (p = 0.02). The abnormal sensitivity to insulin postoperatively rose from 32.1% to 46.4% of cases (p = 0.24), and it occurred in only 11.1% of patients in GLN group when compared to 55.5% in the fasting group (p = 0.02). CONCLUSION: the abbreviation of preoperative fasting for two hours with dextrinomaltose and glutamine improves insulin sensitivity in patients undergoing elective laparoscopic cholecystectomy.