PubMed

Front Microbiol. 2023 Sep 28;14:1264361. doi: 10.3389/fmicb.2023.1264361. eCollection 2023.ABSTRACTBACKGROUND: The results of omic methodologies are often reported as separate datasets. In this study we applied for the first time multi-omic features clustering and pathway enrichment to clarify the biological impact of vitamin B2 supplementation on broiler caeca microbiome.METHODS: The caeca contents of broilers fed +50 and +100 mg/kg vitamin B2 were analyzed by shotgun metagenomic and metabolomic. Latent variables extracted from NMR spectra, as well as taxonomic and functional features profiled from metagenomes, were integrated to characterize the effect of vitamin B2 in modulating caeca microbiome. A pathway-based network was obtained by mapping the observed input genes and compounds, highlighting connected strands of metabolic ways through pathway-enrichment analysis.RESULTS: At day 14, the taxonomic, functional and metabolomic features in the caeca of tested broilers showed some degree of separation between control and treated groups, becoming fully clear at 28 days and persisting up to 42 days. In the caeca of birds belonging to the control group Alistipes spp. was the signature species, while the signature species in the caeca of broilers fed +50 and +100 mg/kg vitamin B2 were Bacteroides fragilis and Lactobacillus crispatus, Lactobacillus reuteri, Ruminococcus torques, Subdoligranum spp., respectively. The pathway enrichment analysis highlighted that the specific biochemical pathways enhanced by the supplementations of vitamin B2 were N-Formyl-L-aspartate amidohydrolase, producing Aspartate and Formate; L-Alanine:2-oxoglutarate amino transferase, supporting the conversion of L-Alanine and 2-Oxoglutarate in Pyruvate and L-Glutamate; 1D-myo-inositol 1/4 phosphate phosphohydrolase, converting Inositol 1/4-phosphate and water in myo-Inositol and Orthophosphate. The results of this study demonstrated that the caeca of birds fed +50 and + 100 mg/kg were those characterized by taxonomic groups more beneficial to the host and with a higher concentration of myo-inositol, formic acid, amino acids and pyruvate involved in glycolysis and amino acid biosynthesis.CONCLUSION: In this study we demonstrated how to perform multi-omic features integration to describe the biochemical mechanisms enhanced by the supplementation of different concentrations of vitamin B2 in the poultry diet. The relationship between vitamin B2 supplementation and myo-inositol production was highlighted in our study for the first time.PMID:37840729 | PMC:PMC10568133 | DOI:10.3389/fmicb.2023.1264361

Front Microbiol. 2023 Sep 28;14:1244519. doi: 10.3389/fmicb.2023.1244519. eCollection 2023.ABSTRACTOBJECTIVE: To investigate the relationship between gut microbiota and the fecal metabolites of hypoxic environments in mice.METHODS: High-fat diet-induced obese mice (n = 20) and normal diet-fed mice (n = 20) were randomly divided into four groups: high altitude obese group (HOB), high altitude normal weight group (HN), low altitude obese group LOB (LOB), and low altitude normal weight group (LN). Fecal samples from each group were 16S rRNA gene sequenced, and five samples from each of the four groups above were selected for non-targeted fecal metabolomics analysis using liquid chromatography-mass spectrometry. The relationship between gut microbiota and fecal metabolites was analyzed using SIMCA 14.1, MetaboAnalyst 5.0 and R 4.1.11.RESULTS: (A) Body weight was significantly lower in the hypoxic obesity group than in the normoxic obesity group. (B) Differences in α-diversity and β-diversity were found in the fecal gut microbiota of mice of different body weights and altitude, and the diversity of gut microbiota was higher in the normal group than in the obese group; the results of the comparison between the two groups showed that Faecalibaculum, Romboutsia, Lactobacillus, and A2 were associated with obesity; Romboutsia was associated with hypoxia. (C) The metabolic profiles of fecal metabolites differed between groups: gut microbiota were associated with nucleotide and amino acid metabolism in the same body groups, while gut microbiota were associated with lipid and amino acid metabolism in the same oxygen concentration groups.CONCLUSION: (a) Gut microbiota diversity was reduced in obese groups. Romboutsia was the dominant microbiota in the hypoxia group. (b) Gut microbiota were associated with nucleotide and amino acid metabolism in the same body weight groups, while they were associated with lipid and amino acid metabolism in the same altitude groups.PMID:37840721 | PMC:PMC10569469 | DOI:10.3389/fmicb.2023.1244519

Trends Analyt Chem. 2023 Nov;168:117300. doi: 10.1016/j.trac.2023.117300. Epub 2023 Sep 20.ABSTRACTMetabolic assays serve as pivotal tools in biomedical research, offering keen insights into cellular physiological and pathological states. While mass spectrometry (MS)-based metabolomics remains the gold standard for comprehensive, multiplexed analyses of cellular metabolites, innovative technologies are now emerging for the targeted, quantitative scrutiny of metabolites and metabolic pathways at the single-cell level. In this review, we elucidate an array of these advanced methodologies, spanning synthetic and surface chemistry techniques, imaging-based methods, and electrochemical approaches. We summarize the rationale, design principles, and practical applications for each method, and underscore the synergistic benefits of integrating single-cell metabolomics (scMet) with other single-cell omics technologies. Concluding, we identify prevailing challenges in the targeted scMet arena and offer a forward-looking commentary on future avenues and opportunities in this rapidly evolving field.PMID:37840599 | PMC:PMC10569257 | DOI:10.1016/j.trac.2023.117300

J Diabetes Res. 2023 Oct 5;2023:9164883. doi: 10.1155/2023/9164883. eCollection 2023.ABSTRACTDiabetic nephropathy (DN) is a metabolic disease wherein chronic hyperglycemia triggers various renal cell dysfunctions, eventually leading to progressive kidney failure. Rosa laevigata Michx. is a traditional Chinese herbal medicine. Many studies have confirmed its antioxidative, anti-inflammatory, and renoprotective effects. However, the effects and mechanisms of Rosa laevigata Michx. polysaccharide (RLP) in DN remain unclear. In this study, a DN mouse model was established to investigate the therapeutic effect of RLP on DN mice. Then, nontargeted metabolomics was used to analyze the potential mechanism of RLP in the treatment of DN. Finally, the effects of RLP on ferroptosis and the PI3K/AKT pathway were investigated. The results demonstrated that RLP effectively alleviated renal injury and reduced inflammation and oxidative stress in the kidney. In addition, nontargeted metabolomic analysis indicated that RLP could modulate riboflavin metabolism and tryptophan metabolism in DN mice. Notably, ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney were also ameliorated following RLP treatment. In conclusion, this study confirmed that RLP had a significant therapeutic effect on DN mice. Furthermore, RLP treatment modulated tryptophan metabolism and inhibited ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney.PMID:37840577 | PMC:PMC10569897 | DOI:10.1155/2023/9164883

Food Funct. 2023 Oct 16. doi: 10.1039/d3fo03199c. Online ahead of print.ABSTRACTYangxian black rice, as one of the ancient Chinese black rice varieties, is widely planted in the Yangxian area of China. This study investigated the physicochemical properties, phenolic content and in vitro digestion profile of Chinese black rice under gradient milling treatment. The chemical composition, color, pasting and thermal properties of black rice with different milling degrees were comprehensively compared. In vitro digestion analysis indicated that cooked rice flour had higher rapidly digestible starch (RDS) and lower resistant starch (RS) contents compared with the uncooked one. Besides, all cooked black rice samples exhibited high predicted glycemic index (pGI) value and whole black rice showed a lower pGI than refined rice. The microstructure and the abundance of phenolic compounds in the solid matrix during different treatments or digestion stages were observed by CLSM. Furthermore, a total of 102 phenolic constituents were absolutely quantified by targeted metabolomics techniques. Methanol extraction and moderate cooking treatment contributed to the release of phenolic compounds from the solid matrix of whole black rice. Besides, compared to the gastric digestion stage, the transition in the intestinal environment caused a decrease in the majority of the analyzed polyphenols. Identifying the phenolic constituents was favorable for a better elucidation of the chemical basis of the function and nutritional value of Chinese black rice.PMID:37840531 | DOI:10.1039/d3fo03199c

J Alzheimers Dis. 2023 Oct 6. doi: 10.3233/JAD-230403. Online ahead of print.ABSTRACTBACKGROUND: Comprehensive treatment of Alzheimer's disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. Personalized, multimodal therapies are needed to best prevent and treat Alzheimer's disease (AD).OBJECTIVE: The Coaching for Cognition in Alzheimer's (COCOA) trial was a prospective randomized controlled trial to test the hypothesis that a remotely coached multimodal lifestyle intervention would improve early-stage AD.METHODS: Participants with early-stage AD were randomized into two arms. Arm 1 (N = 24) received standard of care. Arm 2 (N = 31) additionally received telephonic personalized coaching for multiple lifestyle interventions. The primary outcome was a test of the hypothesis that the Memory Performance Index (MPI) change over time would be better in the intervention arm than in the control arm. The Functional Assessment Staging Test was assessed for a secondary outcome. COCOA collected psychometric, clinical, lifestyle, genomic, proteomic, metabolomic, and microbiome data at multiple timepoints (dynamic dense data) across two years for each participant.RESULTS: The intervention arm ameliorated 2.1 [1.0] MPI points (mean [SD], p = 0.016) compared to the control over the two-year intervention. No important adverse events or side effects were observed.CONCLUSION: Multimodal lifestyle interventions are effective for ameliorating cognitive decline and have a larger effect size than pharmacological interventions. Dietary changes and exercise are likely to be beneficial components of multimodal interventions in many individuals. Remote coaching is an effective intervention for early stage ADRD. Remote interventions were effective during the COVID pandemic.PMID:37840487 | DOI:10.3233/JAD-230403

Small Methods. 2023 Oct 15:e2301179. doi: 10.1002/smtd.202301179. Online ahead of print.ABSTRACTPopulation-level analysis masks significant heterogeneity between individual cells, making it difficult to accurately reflect the true intricacies of life activities. Microfluidics is a technique that can manipulate individual cells effectively and is commonly coupled with a variety of analytical methods for single-cell analysis. Single-cell omics provides abundant molecular information at the single-cell level, fundamentally revealing differences in cell types and biological states among cell individuals, leading to a deeper understanding of cellular phenotypes and life activities. Herein, this work summarizes the microfluidic chips designed for single-cell isolation, manipulation, trapping, screening, and sorting, including droplet microfluidic chips, microwell arrays, hydrodynamic microfluidic chips, and microchips with microvalves. This work further reviews the studies on single-cell proteomics, metabolomics, lipidomics, and multi-omics based on microfluidics and mass spectrometry. Finally, the challenges and future application of single-cell multi-omics are discussed.PMID:37840412 | DOI:10.1002/smtd.202301179

Nat Prod Res. 2023 Oct 15:1-5. doi: 10.1080/14786419.2023.2265535. Online ahead of print.ABSTRACTCallerya speciosa is a perennial edible and medicinal plant belonging to the family Fabaceae. This study was to reveal the similarities and differences between phytochemicals in different parts of C. speciosa using a combination of ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). In addition, the anti-diabetic activity of C. speciosa extracts was explored. A total of 141 compounds were identified and 34 robustly known chemical markers were marked. PCA and heat map analyses revealed that the stems, leaves and pods had similar phytochemical compounds, while compounds in roots and flowers differed from each other and from those in the above ground parts. In addition, extracts of C. speciosa roots and flowers exhibited anti-diabetic activity, which can be applied to the development of anti-diabetic drugs.PMID:37840299 | DOI:10.1080/14786419.2023.2265535

Mol Metab. 2023 Oct 13:101823. doi: 10.1016/j.molmet.2023.101823. Online ahead of print.ABSTRACTOBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD.METHODS: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis.RESULTS: After the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver.CONCLUSIONS: These data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD.PMID:37839774 | DOI:10.1016/j.molmet.2023.101823

J Ethnopharmacol. 2023 Oct 13:117294. doi: 10.1016/j.jep.2023.117294. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined.AIM OF THE STUDY: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism.MATERIALS AND METHODS: The Wistar male rats (7 weeks old; weight 180-200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease.RESULTS: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats.CONCLUSION: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.PMID:37839771 | DOI:10.1016/j.jep.2023.117294

Am J Kidney Dis. 2023 Oct 13:S0272-6386(23)00854-5. doi: 10.1053/j.ajkd.2023.08.015. Online ahead of print.ABSTRACTChronic kidney disease (CKD) and acute kidney injury (AKI) are heterogeneous syndromes defined clinically by serial measures of kidney function. Each condition possesses strong histopathologic associations including glomerular obsolescence or acute tubular necrosis, respectively. Despite such characterization, there remains wide variation in patient outcomes and treatment responses. Precision medicine efforts, as exemplified by the Kidney Precision Medicine Project (KPMP), have begun to establish evolving, spatially-anchored, cellular and molecular atlases of the cell types, states and niches of the kidney in health and disease. The KPMP atlas provides molecular context for CKD and AKI disease drivers, and will help define subtypes of disease that are not readily apparent from canonical functional or histopathologic characterization, but instead appreciable through advanced clinical phenotyping, pathomic, transcriptomic, proteomic, epigenomic, and metabolomic interrogation of kidney biopsy samples. This perspective outlines the structure of the KPMP, its approach to the integration of these diverse datasets, and its major outputs relevant to future patient care.PMID:37839688 | DOI:10.1053/j.ajkd.2023.08.015

Am J Obstet Gynecol MFM. 2023 Oct 13:101188. doi: 10.1016/j.ajogmf.2023.101188. Online ahead of print.ABSTRACTBACKGROUND: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment.OBJECTIVE: To investigate whether structured lifestyle interventions based on a Mediterranean diet or Mindfulness-Based Stress Reduction during pregnancy are associated with differences in fetal and neonatal brain development.STUDY DESIGN: This is a secondary analysis of the randomized clinical trial IMPACT BCN, conducted in Barcelona, Spain, 2017-2020. Singleton pregnancies were randomly allocated into three groups: Mediterranean diet intervention, stress reduction program or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week Mindfulness-Based Stress Reduction program adapted for pregnancy. Magnetic resonance (MRI) of 90 fetal brains was performed at 36-39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale (NBAS) in 692 newborns at 1-3 months. Fetal outcomes were the total brain volume and lobular/regional volumes obtained from a 3D reconstruction and semiautomatic segmentation of MRI images. Neonatal outcomes were the six clusters' scores of the NBAS. Multiple regression analyses were conducted to assess the association between the interventions and fetal/neonatal outcomes.RESULTS: Compared with the usual care group, Mediterranean diet offspring had a larger fetal total brain volume [mean (SD); 284.11 (23.92) cm3vs. 294.01 (26.29) cm3; p=0.04], corpus callosum [mean (SD) 1.16 (0.19) cm3vs. 1.26 (0.22) cm3; p= 0.03], right frontal lobe [44.20 (4.09) cm3vs. 46.60 (4.69) cm3; p=0.02] volumes at MRI, and higher scores in the NBAS clusters of autonomic stability [mean (SD); 7.4 (0.9) vs. 7.6 (0.7); p=0.04], social-interactive [mean (SD); 7.5 (1.5) vs. 7.8 (1.3); p= 0.03], and range of state [mean (SD); 4.3 (1.3) vs. 4.5 (1.0); p=0.04]. Compared to the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume [1.63 (0.32) m3vs. 1.79 (0.30) cm3; p=0.03] at MRI, and higher scores at NBAS in the neonatal regulation of state [mean (SD); 6.0 (1.8) vs. 6.5 (1.5); p<0.01].CONCLUSIONS: Maternal structured lifestyle interventions based on promotion of Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development.PMID:37839546 | DOI:10.1016/j.ajogmf.2023.101188

Sci Total Environ. 2023 Oct 13:167833. doi: 10.1016/j.scitotenv.2023.167833. Online ahead of print.ABSTRACTOxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of polycyclic aromatic derivatives with oxygen-containing functional groups that induce oxidative stress and mutations. However, studies of the carcinogenic and metabolic effects of OPAHs are limited. In this study, we analyzed the carcinogenic effects of four different OPAHs and found that 9-fluorenone (FLO), 9,10-anthraquinone (AQ), and 7,12-benz(a)anthraquinone (BAQ) promoted cell invasion and metastasis via epithelial-mesenchymal transition (EMT) and induced endothelial cell angiogenesis by affecting the expression of vascular endothelial growth factor (VEGF), angiopoietin (ANG), and platelet-derived growth factor (PDGF), whereas 1,8-naphthalic anhydride (NAD) did not show significant carcinogenic effects. In addition, combined with metabolomic analysis, we found that the tumor-promoting effects of different OPAHs were related to their effects on the metabolome, especially the metabolism of glutathione related to oxidative stress. These results provide an experimental basis for studying the carcinogenic and metabolic effects of OPAHs, and an important reference for comprehensively assessing the ecological and health risks of this compounds.PMID:37839476 | DOI:10.1016/j.scitotenv.2023.167833

J Plant Physiol. 2023 Oct 7;290:154116. doi: 10.1016/j.jplph.2023.154116. Online ahead of print.ABSTRACTA plant's genome encodes enzymes, transporters and many other proteins which constitute metabolism. Interactions of plants with their environment shape their growth, development and resilience towards adverse conditions. Although genome sequencing technologies and applications have experienced triumphantly rapid development during the last decades, enabling nowadays a fast and cheap sequencing of full genomes, prediction of metabolic phenotypes from genotype × environment interactions remains, at best, very incomplete. The main reasons are a lack of understanding of how different levels of molecular organisation depend on each other, and how they are constituted and expressed within a setup of growth conditions. Phenotypic plasticity, e.g., of the genetic model plant Arabidopsis thaliana, has provided important insights into plant-environment interactions and the resulting genotype x phenotype relationships. Here, we summarize previous and current findings about plant development in a changing environment and how this might be shaped and reflected in metabolism and its regulation. We identify current challenges in the study of plant development and metabolic regulation and provide an outlook of how methodological workflows might support the application of findings made in model systems to crops and their cultivation.PMID:37839392 | DOI:10.1016/j.jplph.2023.154116

Talanta. 2023 Oct 7;268(Pt 1):125296. doi: 10.1016/j.talanta.2023.125296. Online ahead of print.ABSTRACTBladder cancer (BC) represents a significant global health concern, for which early detection is essential to improve patient outcomes. This review evaluates the potential of the urinary volatile organic compounds (VOCs) as biomarkers for detecting and staging BC. The methods used include gas chromatography-mass spectrometry (GC-MS)-based metabolomics and electronic-nose (e-nose) sensors. The GC-MS studies that have been published reveal diverse results in terms of diagnostic performance. The sensitivities range from 27 % to an impressive 97 %, while specificities vary between 43 % and 94 %. Furthermore, the accuracies reported in these studies range from 80 to 89 %. In the urine of BC patients, a total of 80 VOCs were discovered to be significantly altered when compared to controls. These VOCs encompassed a variety of chemical classes such as alcohols, aldehydes, alkanes, aromatic compounds, fatty acids, ketones, and terpenoids, among others. Conversely, e-nose-based studies displayed sensitivities from 60 to 100 %, specificities from 53 to 96 %, and accuracies from 65 to 97 %. Interestingly, conductive polymer-based sensors performed better, followed by metal oxide semiconductor and optical sensors. GC-MS studies have shown improved performance in detecting early stages and low-grade tumors, providing valuable insights into staging. Based on these findings, VOC-based diagnostic tools hold great promise for early BC detection and staging. Further studies are needed to validate biomarkers and their classification performance. In the future, advancements in VOC profiling technologies may significantly contribute to improving the overall survival and quality of life for BC patients.PMID:37839328 | DOI:10.1016/j.talanta.2023.125296

Talanta. 2023 Sep 29;268(Pt 1):125249. doi: 10.1016/j.talanta.2023.125249. Online ahead of print.ABSTRACTEstimates of post-mortem interval (PMI), which often serve as pivotal evidence in forensic contexts, are fundamentally based on assessments of variability among diverse molecular markers (including proteins and metabolites), their correlations, and their temporal changes in post-mortem organisms. Nevertheless, the present approach to estimating the PMI is not comprehensive and exhibits poor performance. We developed an innovative approach that integrates multi-omics and artificial intelligence, using multimolecular, multimarker, and multidimensional information to accurately describe the intricate biological processes that occur after death, ultimately enabling inference of the PMI. Called the multi-omics stacking model (MOSM), it combines metabolomics, protein microarray electrophoresis, and fourier transform-infrared spectroscopy data. It shows improved prediction accuracy of the PMI, which is urgently needed in the forensic field. It achieved an accuracy of 0.93, generalized area under the receiver operating characteristic curve of 0.98, and minimum mean absolute error of 0.07. The MOSM integration framework not only considers multiple markers but also incorporates machine-learning models with distinct algorithmic principles. The diversity of biological mechanisms and algorithmic models further ensures the generalizability and robustness of PMI estimation.PMID:37839320 | DOI:10.1016/j.talanta.2023.125249

Food Chem. 2023 Oct 10;436:137719. doi: 10.1016/j.foodchem.2023.137719. Online ahead of print.ABSTRACTProbiotic-fermented plant-based foods are associated with weight loss. Here, we hypothesized probiotic-fermented tomato (FT) as a functional food with potential to alleviate obesity, thus the obesity-alleviating effects and mechanisms of FT on high-fat diet-induced obese mice were explored via biochemical, gut microbiome, and serum metabolomics analysis. The results showed that FT performed better than unfermented tomato in reducing body weight gain and fat accumulation, improving dyslipidemia and glucose homeostasis, and relieving inflammation and adipocytokine dysregulation. Particularly, live probiotic-fermented tomato (LFT) was associated with improved diversity, composition, and structure of gut microbiota, suppressed obesity-related genera growth (e.g., Clostridium, Olsenella, and Mucispirillum), and promoted beneficial genera growth (e.g., Roseburia, Coprococcus, and Oscillospira), which were associated negatively with body weight, TC, TG, and TNF-α levels. Additionally, LFT was associated with positive changes in glycerophospholipids, sphingolipids, unsaturated fatty acids, and amino acids levels. Collectively, as a functional food, LFT possessed potential for obesity alleviation.PMID:37839120 | DOI:10.1016/j.foodchem.2023.137719

Food Chem. 2023 Oct 13;436:137633. doi: 10.1016/j.foodchem.2023.137633. Online ahead of print.ABSTRACTIn this work, the impact of gluten free (GF) breads enriched with spirulina on the ecology of the colon microbiota of non-celiac volunteers was investigated. Simulation of digestion of GF breads was conducted with an in vitro gut model. Microbiomics and metabolomics analyses were done during colon fermentations to study the modulation of the microbiota. From the results, a general increase in Proteobacteria and no reduction of detrimental microbial metabolites were observed in any conditions. Notwithstanding, algae enriched sourdough breads showed potential functionalities, as the improvement of some health-related ecological indicators, like i) microbiota eubiosis; ii) production of bioactive volatile organic fatty acids; iii) production of bioactives terpenes. Our results indicate that a sourdough fermentation and algae enrichment can mitigate the negative effect of GF breads on gut microbiota of non-celiac consumers.PMID:37839115 | DOI:10.1016/j.foodchem.2023.137633

Diabetes Metab Res Rev. 2023 Oct 15:e3734. doi: 10.1002/dmrr.3734. Online ahead of print.ABSTRACTCONTEXT: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high-risk patients for referral to the most aggressive and costly prevention strategies is needed.OBJECTIVE: To validate in type 2 diabetes the association with all-cause mortality of a 14-metabolite score (14-MS) previously reported in the general population and whether this score can be used to improve well-established mortality prediction models.METHODS: This is a sub-study consisting of 600 patients from the "Sapienza University Mortality and Morbidity Event Rate" (SUMMER) study in diabetes, a prospective multicentre investigation on all-cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high-throughput proton nuclear magnetic resonance metabolomics.RESULTS: In type 2 diabetes, the 14-MS showed a significant (p < 0.0001) association with mortality, which was lower (p < 0.0001) than that reported in the general population. This difference was mainly due to two metabolites (histidine and ratio of polyunsaturated fatty acids to total fatty acids) with an effect size that was significantly (p = 0.01) lower in diabetes than in the general population. A parsimonious 12-MS (i.e. lacking the 2 metabolites mentioned above) improved patient discrimination and classification of two well-established mortality prediction models (p < 0.0001 for all measures).CONCLUSIONS: The metabolomic signature of mortality in the general population is only partially effective in type 2 diabetes. Prediction markers developed and validated in the general population must be revalidated if they are to be used in patients with diabetes.PMID:37839040 | DOI:10.1002/dmrr.3734

NPJ Sci Food. 2023 Oct 14;7(1):54. doi: 10.1038/s41538-023-00231-0.ABSTRACTDue to the rampant rise in obesity and diabetes, consumers are desperately seeking for ways to reduce their sugar intake, but to date there are no options that are both accessible and without sacrifice of palatability. One of the most promising new ingredients in the food system as a non-nutritive sugar substitute with near perfect palatability is D-psicose. D-psicose is currently produced using an in vitro enzymatic isomerization of D-fructose, resulting in low yield and purity, and therefore requiring substantial downstream processing to obtain a high purity product. This has made adoption of D-psicose into products limited and results in significantly higher per unit costs, reducing accessibility to those most in need. Here, we found that Escherichia coli natively possesses a thermodynamically favorable pathway to produce D-psicose from D-glucose through a series of phosphorylation-epimerization-dephosphorylation steps. To increase carbon flux towards D-psicose production, we introduced a series of genetic modifications to pathway enzymes, central carbon metabolism, and competing metabolic pathways. In an attempt to maximize both cellular viability and D-psicose production, we implemented methods for the dynamic regulation of key genes including clustered regularly interspaced short palindromic repeats inhibition (CRISPRi) and stationary-phase promoters. The engineered strains achieved complete consumption of D-glucose and production of D-psicose, at a titer of 15.3 g L-1, productivity of 2 g L-1 h-1, and yield of 62% under test tube conditions. These results demonstrate the viability of whole-cell catalysis as a sustainable alternative to in vitro enzymatic synthesis for the accessible production of D-psicose.PMID:37838768 | DOI:10.1038/s41538-023-00231-0