PubMed

Nat Rev Nephrol. 2023 Apr 11. doi: 10.1038/s41581-023-00705-0. Online ahead of print.ABSTRACTScientific reductionism has been the basis of disease classification and understanding for more than a century. However, the reductionist approach of characterizing diseases from a limited set of clinical observations and laboratory evaluations has proven insufficient in the face of an exponential growth in data generated from transcriptomics, proteomics, metabolomics and deep phenotyping. A new systematic method is necessary to organize these datasets and build new definitions of what constitutes a disease that incorporates both biological and environmental factors to more precisely describe the ever-growing complexity of phenotypes and their underlying molecular determinants. Network medicine provides such a conceptual framework to bridge these vast quantities of data while providing an individualized understanding of disease. The modern application of network medicine principles is yielding new insights into the pathobiology of chronic kidney diseases and renovascular disorders by expanding the understanding of pathogenic mediators, novel biomarkers and new options for renal therapeutics. These efforts affirm network medicine as a robust paradigm for elucidating new advances in the diagnosis and treatment of kidney disorders.PMID:37041415 | DOI:10.1038/s41581-023-00705-0

Metabolomics. 2023 Apr 11;19(4):39. doi: 10.1007/s11306-023-01998-9.ABSTRACTINTRODUCTION: The metabolomic profiles of Soldiers entering the U.S. Special Forces Assessment and Selection course (SFAS) have not been evaluated.OBJECTIVES: To compare pre-SFAS blood metabolomes of Soldiers selected during SFAS versus those not selected, and explore the relationships between the metabolome, physical performance, and diet quality.METHODS: Fasted blood samples and food frequency questionnaires were collected from 761 Soldiers prior to entering SFAS to assess metabolomic profiles and diet quality, respectively. Physical performance was assessed throughout SFAS.RESULTS: Between-group differences (False Discovery Rate < 0.05) in 108 metabolites were detected. Selected candidates had higher levels of compounds within xenobiotic, pentose phosphate, and corticosteroid metabolic pathways, while non-selected candidates had higher levels of compounds potentially indicative of oxidative stress (i.e., sphingomyelins, acylcarnitines, glutathione, amino acids). Multiple compounds higher in non-selected versus selected candidates included: 1-carboxyethylphenylalanine; 4-hydroxy-nonenal-glutathione; α-hydroxyisocaproate; hexanoylcarnitine; sphingomyelin and were associated with lower diet quality and worse physical performance. CONCLUSION: Candidates selected during SFAS had higher pre-SFAS levels of circulating metabolites that were associated with resistance to oxidative stress, higher physical performance and higher diet quality. In contrast, non-selected candidates had higher levels of metabolites potentially indicating elevated oxidative stress. These findings indicate that Soldiers who were selected for continued Special Forces training enter the SFAS course with metabolites associated with healthier diets and better physical performance. Additionally, the non-selected candidates had higher levels of metabolites that may indicate elevated oxidative stress, which could result from poor nutrition, non-functional overreaching/overtraining, or incomplete recovery from previous physical activity.PMID:37041398 | DOI:10.1007/s11306-023-01998-9

Cell Mol Immunol. 2023 Apr 12. doi: 10.1038/s41423-023-01011-2. Online ahead of print.ABSTRACTThe imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.PMID:37041314 | DOI:10.1038/s41423-023-01011-2

Sci Rep. 2023 Apr 11;13(1):5854. doi: 10.1038/s41598-023-33067-5.ABSTRACTLess invasive rumen sampling methods, such as oro-esophageal tubing, became widely popular for exploring the rumen microbiome and metabolome. However, it remains unclear if such methods represent well the rumen contents from the rumen cannula technique. Herein, we characterized the microbiome and metabolome in the rumen content collected by an oro-esophageal tube and by rumen cannula in ten multiparous lactating Holstein cows. The 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Untargeted metabolome was characterized using gas chromatography of a time-of-flight mass spectrometer. Bacteroidetes, Firmicutes, and Proteobacteria were the top three most abundant phyla representing ~ 90% of all samples. Although the pH of oro-esophageal samples was greater than rumen cannula, we found no difference in alpha and beta-diversity among their microbiomes. The overall metabolome of oro-esophageal samples was slightly different from rumen cannula samples yet more closely related to the rumen cannula content as a whole, including its fluid and particulate fractions. Enrichment pathway analysis revealed a few differences between sampling methods, such as when evaluating unsaturated fatty acid pathways in the rumen. The results of the current study suggest that oro-esophageal sampling can be a proxy to screen the 16S rRNA rumen microbiome compared to the rumen cannula technique. The variation introduced by the 16S rRNA methodology may be mitigated by oro-esophageal sampling and the possibility of increasing experimental units for a more consistent representation of the overall microbial population. Studies should consider an under or over-representation of metabolites and specific metabolic pathways depending on the sampling method.PMID:37041192 | DOI:10.1038/s41598-023-33067-5

Cell Metab. 2023 Apr 4:S1550-4131(23)00091-8. doi: 10.1016/j.cmet.2023.03.013. Online ahead of print.ABSTRACTNonalcoholic steatohepatitis (NASH) prevalence is rising with no pharmacotherapy approved. A major hurdle in NASH drug development is the poor translatability of preclinical studies to safe/effective clinical outcomes, and recent failures highlight a need to identify new targetable pathways. Dysregulated glycine metabolism has emerged as a causative factor and therapeutic target in NASH. Here, we report that the tripeptide DT-109 (Gly-Gly-Leu) dose-dependently attenuates steatohepatitis and fibrosis in mice. To enhance the probability of successful translation, we developed a nonhuman primate model that histologically and transcriptionally mimics human NASH. Applying a multiomics approach combining transcriptomics, proteomics, metabolomics, and metagenomics, we found that DT-109 reverses hepatic steatosis and prevents fibrosis progression in nonhuman primates, not only by stimulating fatty acid degradation and glutathione formation, as found in mice, but also by modulating microbial bile acid metabolism. Our studies describe a highly translatable NASH model and highlight the need for clinical evaluation of DT-109.PMID:37040763 | DOI:10.1016/j.cmet.2023.03.013

Research (Wash D C). 2023;6:0036. doi: 10.34133/research.0036. Epub 2023 Jan 13.ABSTRACTUnderstanding the details of metabolic reprogramming in hepatocellular carcinoma (HCC) is critical to improve stratification for therapy. Both multiomics analysis and cross-cohort validation were performed to investigate the metabolic dysregulation of 562 HCC patients from 4 cohorts. On the basis of the identified dynamic network biomarkers, 227 substantial metabolic genes were identified and a total of 343 HCC patients were classified into 4 heterogeneous metabolic clusters with distinct metabolic characteristics: cluster 1, the pyruvate subtype, associated with upregulated pyruvate metabolism; cluster 2, the amino acid subtype, with dysregulated amino acid metabolism as the reference; cluster 3, the mixed subtype, in which lipid metabolism, amino acid metabolism, and glycan metabolism are dysregulated; and cluster 4, the glycolytic subtype, associated with the dysregulated carbohydrate metabolism. These 4 clusters showed distinct prognoses, clinical characteristics and immune cell infiltrations, which was further validated by genomic alterations, transcriptomics, metabolomics, and immune cell profiles in the other 3 independent cohorts. Besides, the sensitivity of different clusters to metabolic inhibitors varied depending on their metabolic features. Importantly, cluster 2 is rich in immune cells in tumor tissues, especially programmed cell death protein 1 (PD-1)-expressing cells, which may be due to the tryptophan metabolism disorders, and potentially benefiting more from PD-1 treatment. In conclusion, our results suggest the metabolic heterogeneity of HCC and make it possible to treat HCC patients precisely and effectively on specific metabolic characteristics.PMID:37040510 | PMC:PMC10076022 | DOI:10.34133/research.0036

Research (Wash D C). 2023;6:0019. doi: 10.34133/research.0019. Epub 2023 Jan 10.ABSTRACTHeart failure (HF), leading as one of the main causes of mortality, has become a serious public health issue with high prevalence around the world. Single cardiomyocyte (CM) metabolomics promises to revolutionize the understanding of HF pathogenesis since the metabolic remodeling in the human hearts plays a vital role in the disease progression. Unfortunately, current metabolic analysis is often limited by the dynamic features of metabolites and the critical needs for high-quality isolated CMs. Here, high-quality CMs were directly isolated from transgenic HF mice biopsies and further employed in the cellular metabolic analysis. The lipids landscape in individual CMs was profiled with a delayed extraction mode in time-of-flight secondary ion mass spectrometry. Specific metabolic signatures were identified to distinguish HF CMs from the control subjects, presenting as possible single-cell biomarkers. The spatial distributions of these signatures were imaged in single cells, and those were further found to be strongly associated with lipoprotein metabolism, transmembrane transport, and signal transduction. Taken together, we systematically studied the lipid metabolism of single CMs with a mass spectrometry imaging method, which directly benefited the identification of HF-associated signatures and a deeper understanding of HF-related metabolic pathways.PMID:37040505 | PMC:PMC10076023 | DOI:10.34133/research.0019

Rice (N Y). 2023 Apr 11;16(1):19. doi: 10.1186/s12284-023-00636-1.ABSTRACTBACKGROUND: As climate change events become more frequent, drought is an increasing threat to agricultural production and food security. Crop rhizosphere microbiome and root exudates are critical regulators for drought adaptation, yet our understanding on the rhizosphere bacterial communities and root exudate composition as affected by drought stress is far from complete. In this study, we performed 16S rRNA gene amplicon sequencing and widely targeted metabolomic analysis of rhizosphere soil and root exudates from two contrasting rice genotypes (Nipponbare and Luodao 998) exposed to drought stress.RESULTS: A reduction in plant phenotypes was observed under drought, and the inhibition was greater for roots than for shoots. Additionally, drought exerted a negligible effect on the alpha diversity of rhizosphere bacterial communities, but obviously altered their composition. In particular, drought led to a significant enrichment of Actinobacteria but a decrease in Firmicutes. We also found that abscisic acid in root exudates was clearly higher under drought, whereas lower jasmonic acid and L-cystine concentrations. As for plant genotypes, variations in plant traits of the drought-tolerant genotype Luodao 998 after drought were smaller than those of Nipponbare. Interestingly, drought triggered an increase in Bacillus, as well as an upregulation of most organic acids and a downregulation of all amino acids in Luodao 998. Notably, both Procrustes analysis and Mantel test demonstrated that rhizosphere microbiome and root exudate metabolomic profiles were highly correlated. A number of differentially abundant genera responded to drought and genotype, including Streptomyces, Bacillus and some members of Actinobacteria, were significantly associated with organic acid and amino acid contents in root exudates. Further soil incubation experiments showed that Streptomyces was regulated by abscisic acid and jasmonic acid under drought.CONCLUSIONS: Our results reveal that both drought and genotype drive changes in the compositions of rice rhizosphere bacterial communities and root exudates under the greenhouse condition, and that organic acid exudation and suppression of amino acid exudation to select specific rhizosphere bacterial communities may be an important strategy for rice to cope with drought. These findings have important implications for improving the adaptability of rice to drought from the perspective of plant-microbe interactions.PMID:37039929 | DOI:10.1186/s12284-023-00636-1

Appl Environ Microbiol. 2023 Apr 11:e0040623. doi: 10.1128/aem.00406-23. Online ahead of print.ABSTRACTClostridium thermocellum, a promising candidate for consolidated bioprocessing, has been subjected to numerous engineering strategies for enhanced bioethanol production. Measurements of intracellular metabolites at substrate concentrations high enough (>50 g/L) to allow the production of industrially relevant titers of ethanol would inform efforts toward this end but have been difficult due to the production of a viscous substance that interferes with the filtration and quenching steps during metabolite extraction. To determine whether this problem is unique to C. thermocellum, we performed filtration experiments with other organisms that have been engineered for high-titer ethanol production, including Escherichia coli and Thermoanaerobacterium saccharolyticum. We addressed the problem through a series of improvements, including active pH control (to reduce problems with viscosity), investigation of different filter materials and pore sizes (to increase the filtration capacity), and correction for extracellular metabolite concentrations, and we developed a technique for more accurate intracellular metabolite measurements at elevated substrate concentrations. IMPORTANCE The accurate measurement of intracellular metabolites (metabolomics) is an integral part of metabolic engineering for the enhanced production of industrially important compounds and a useful technique to understand microbial physiology. Previous work tended to focus on model organisms under laboratory conditions. As we try to perform metabolomic studies with a wider range of organisms under conditions that more closely represent those found in nature or industry, we have found limitations in existing techniques. For example, fast filtration is an important step in quenching metabolism in preparation for metabolite extraction; however, it does not work for cultures of C. thermocellum at high substrate concentrations. In this work, we characterize the extent of the problem and develop techniques to overcome it.PMID:37039651 | DOI:10.1128/aem.00406-23

Elife. 2023 Apr 11;12:e81080. doi: 10.7554/eLife.81080. Online ahead of print.ABSTRACTOngoing climate change has caused rapidly increasing temperatures, and an unprecedented decline in seawater pH, known as ocean acidification. Increasing temperatures are redistributing species towards higher and cooler latitudes which are most affected by ocean acidification. Whilst the persistence of intertidal species in cold environments is related to their capacity to resist sub-zero air temperatures, studies have never considered the interacting impacts of ocean acidification and freeze stress on species survival and distribution. Here, a full-factorial experiment was used to study whether ocean acidification increases mortality in subtidal Mytilus trossulus and subtidal M. galloprovincialis, and intertidal M. trossulus following sub-zero air temperature exposure. We examined physiological processes behind variation in freeze tolerance using 1H NMR metabolomics, analyses of fatty acids, and amino acid composition. We show that low pH conditions (pH = 7.5) significantly decrease freeze tolerance in both intertidal and subtidal populations of Mytilus spp. Under current day pH conditions (pH = 7.9), intertidal M. trossulus was more freeze tolerant than subtidal M. trossulus and subtidal M. galloprovincialis. Conversely, under low pH conditions, subtidal M. trossulus was more freeze tolerant than the other mussel categories. Differences in the concentration of various metabolites (cryoprotectants), or in the composition of amino acids and cell membrane phospholipid fatty acids could not explain the decrease in survival. These results suggest that ocean acidification can offset the poleward range expansions facilitated by warming, and that reduced freeze tolerance could result in a range contraction if temperatures become lethal at the equatorward edge.PMID:37039622 | DOI:10.7554/eLife.81080

Am J Physiol Lung Cell Mol Physiol. 2023 Apr 11. doi: 10.1152/ajplung.00439.2022. Online ahead of print.ABSTRACTRadiation-induced lung injury is a consequence of therapeutic irradiation (TR) for thoracic cancers. Studies report that up to 80% of patients who undergo TR will have CT-detectable interstitial lung abnormalities, and strategies to limit the risk of RILI may make radiotherapy less effective at treating cancer. Our lab and others have reported that lung tissue from patients with idiopathic pulmonary fibrosis exhibit metabolic defects including increased glycolysis and lactate production. Here, we hypothesized that patients with radiation-induced lung damage will exhibit distinct changes in lung metabolism that may be associated with incidence of fibrosis. Using liquid chromatography/tandem mass spectrometry to identify metabolic compounds, we analyzed exhaled breath condensate (EBC) in subjects with CT-confirmed lung lesions after TR for lung cancer, compared to healthy subjects, smokers, and cancer patients who had not yet received TR. The lung metabolomic profile of the fibrosis case group was significantly different from the 3 control groups. Along with increased levels of lactate, pathway enrichment analysis revealed that EBC from the case patients exhibited upregulations of the fatty acid oxidation and glutamate pathways. As radiation induces aerobic glycolysis and production of lactate which drives myofibroblast differentiation, our results support the hypothesis that preferential conversion of pyruvate to lactate deprives the tricarboxylic acid cycle of a key input, requiring compensatory upregulation of alternative energy inputs to meet the metabolic demands of chronic wound repair. Utilizing an 'omics' approach to probe lung disease in a non-invasive manner could inform future mechanistic investigations and development of novel therapeutic targets.PMID:37039378 | DOI:10.1152/ajplung.00439.2022

Food Funct. 2023 Apr 11. doi: 10.1039/d2fo03722j. Online ahead of print.ABSTRACTAs a class of bioactive and toxic compounds widely present in foodstuffs, the health effects of dietary exposure to β-carboline heterocyclic amines (HAs) have not been elucidated. Based on our previous research that a typical β-carboline HA (harmane) affects blood glucose metabolism and organ dysfunction, the present study mainly focused on the health effects of dietary exposure to harmane in diabetic Goto-Kakizaki (GK) rats. Twenty-four GK rats were administered daily with harmane (0.1 mg per kg body weight) for eight weeks. A comprehensive evaluation of the health effects of harmane was conducted on serum biochemistry, histopathology, and GC-TOF-MS-based metabolomics. The results showed that harmane exerts non-significant effects on the blood glucose metabolism of GK rats. However, it did cause pathological damage to gastrocnemius nerves and showed adverse effects on brain neurons by significantly activating astrocytes and downregulating brain-derived neurotrophic factor (BDNF), which are potential mechanisms related to the disruption of the normal glutamine-glutamate/γ-aminobutyric acid cycle. Moreover, an increased value of AST and urea, alterations in the amino acid, carbohydrate, purine, pyrimidine, and gut microbiota metabolism as well as the tricarboxylic acid (TCA) cycle could be associated with kidney, liver, and gut dysfunction. Our results suggest that given the role of harmane in nerve injury in GK rats, reducing the production and consumption of β-carboline heterocyclic amines in our daily diets should be considered.PMID:37039336 | DOI:10.1039/d2fo03722j

Mol Omics. 2023 Apr 11. doi: 10.1039/d3mo00015j. Online ahead of print.ABSTRACTRoxadustat (FG-4592) is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) prescribed to patients with low hemoglobin associated with chronic kidney disease. Due to the various HIF-mediated adaptive responses, FG-4592 has attracted significant interest for therapeutic use against various diseases. However, the clinical application of Roxadustat remains limited due to a lack of understanding of its underlying mechanisms. Herein, we performed label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS-MS) proteomics and un-targeted metabolomics to study the protein and metabolite alterations in the urine of renal anemia patients before and after Roxadustat therapy. The results were validated by parallel reaction monitoring (PRM). A total of 46 proteins (including 15 upregulated and 31 downregulated proteins) and 207 metabolites were significantly altered after Roxadustat treatment in urine samples obtained from renal anemia patients. Then, the altered proteins were further validated by PRM. Finally, proteomics combined with metabolomics analysis revealed that the Ras signalling pathway, cysteine and methionine metabolism, arginine and proline metabolism, and cholesterol metabolism were the main pathways altered by Roxadustat treatment. The multi-omics analysis revealed that Roxadustat could alter the protein expression and reverse the potential metabolic changes to exert hypotensive, lipid metabolic regulation, and renoprotective effects in clinical practice.PMID:37039271 | DOI:10.1039/d3mo00015j

Food Funct. 2023 Apr 11. doi: 10.1039/d2fo03933h. Online ahead of print.ABSTRACTSulfated polysaccharides from sea cucumber Stichopus japonicus (SCSPsj) have been found to modulate the gut microbiota by promoting the growth of probiotics. However, the effects of the combination of SCSPsj and probiotics are still less known. Thus, the present study aimed to investigate the effects of SCSPsj and Lactobacillus gasseri on gut microbiota-altered mice through gut microbiota and metabolomics analysis. In the present study, supplementation with SCSPsj, L. gasseri or the combination of SCSPsj and L. gasseri could effectively ameliorate the body weight gain and fat accumulation in gut microbiota-altered mice treated with low-dose penicillin. The better effect of the combination of SCSPsj and L. gasseri is attributed to the synergistic effect of SCSPsj and L. gasseri. 16S rRNA sequencing revealed that the combination of SCSPsj and L. gasseri can synergistically improve gut microbiota dysbiosis by increasing Lactobacillus and reducing Coriobacteriaceae_UCG-002. Furthermore, metabolomics results revealed that the combination of SCSPsj and L. gasseri can alleviate metabolic disorders by reducing the levels of lipid and lipid-like molecules in the serum samples, such as trans-vaccenic acid and 3β-hydroxy-5-cholestene. Our findings have proved that the combination of SCSPsj and L. gasseri can benefit host health attributed to the synergistic effect, which is conducive to further application in functional food.PMID:37039235 | DOI:10.1039/d2fo03933h

Gigascience. 2022 Dec 28;12:giad021. doi: 10.1093/gigascience/giad021.ABSTRACTMass spectrometry imaging (MSI), which localizes molecules in a tag-free, spatially resolved manner, is a powerful tool for the understanding of underlying biochemical mechanisms of biological phenomena. When analyzing MSI data, it is essential to delineate regions of interest (ROIs) that correspond to tissue areas of different anatomical or pathological labels. Spatial segmentation, obtained by clustering MSI pixels according to their mass spectral similarities, is a popular approach to automate ROI definition. However, how to select the number of clusters (#Clusters), which determines the granularity of segmentation, remains to be resolved, and an inappropriate #Clusters may lead to ROIs not biologically real. Here we report a multimodal fusion strategy to enable an objective and trustworthy selection of #Clusters by utilizing additional information from corresponding histology images. A deep learning-based algorithm is proposed to extract "histomorphological feature spectra" across an entire hematoxylin and eosin image. Clustering is then similarly performed to produce histology segmentation. Since ROIs originating from instrumental noise or artifacts would not be reproduced cross-modally, the consistency between histology and MSI segmentation becomes an effective measure of the biological validity of the results. So, #Clusters that maximize the consistency is deemed as most probable. We validated our strategy on mouse kidney and renal tumor specimens by producing multimodally corroborated ROIs that agreed excellently with ground truths. Downstream analysis based on the said ROIs revealed lipid molecules highly specific to tissue anatomy or pathology. Our work will greatly facilitate MSI-mediated spatial lipidomics, metabolomics, and proteomics research by providing intelligent software to automatically and reliably generate ROIs.PMID:37039115 | DOI:10.1093/gigascience/giad021

Crit Rev Food Sci Nutr. 2023 Apr 11:1-29. doi: 10.1080/10408398.2023.2197066. Online ahead of print.ABSTRACTProbiotics are amply studied and applied dietary supplements of greater consumer acceptance. Nevertheless, the emerging evidence on probiotics-mediated potential risks, especially among immunocompromised individuals, necessitates careful and in-depth safety studies. The traditional probiotic safety evaluation methods investigate targeted phenotypic traits, such as virulence factors and antibiotic resistance. However, the rapid innovation in omics technologies has offered an impactful means to ultimately sequence and unknot safety-related genes or their gene products at preliminary levels. Further validating the genome features using an array of phenotypic tests would provide an absolute realization of gene expression dynamics. For safety studies in animal models, the in vivo toxicity evaluation guidelines of chemicals proposed by the Organization for Economic Co-operation and Development (OECD) have been meticulously adopted in probiotic research. Future research should also focus on coupling genome-scale safety analysis and establishing a link to its transcriptome, proteome, or metabolome for a fine selection of safe probiotic strains. Considering the studies published over the years, it can be inferred that the safety of probiotics is strain-host-dose-specific. Taken together, an amalgamation of in silico, in vitro, and in vivo approaches are necessary for a fine scale selection of risk-free probiotic strain for use in human applications.PMID:37039078 | DOI:10.1080/10408398.2023.2197066

Future Microbiol. 2023 Apr 11. doi: 10.2217/fmb-2022-0261. Online ahead of print.NO ABSTRACTPMID:37039024 | DOI:10.2217/fmb-2022-0261

Mol Nutr Food Res. 2023 Apr 11:e2200620. doi: 10.1002/mnfr.202200620. Online ahead of print.ABSTRACTSCOPE: Effective strategies for tailoring dietary advice to individuals are urgently needed. We investigate the effectiveness of personalised nutrition advice delivered using a metabotype framework in improving dietary quality and metabolic health biomarkers compared to population-level advice.MATERIALS AND RESULTS: A 12-week parallel randomised controlled trial was performed with 107 healthy adults. Individuals in the personalised group were classified into metabotypes using four marker (triacylglycerol, HDL-cholesterol, total cholesterol and glucose) and received dietary advice from decision tree algorithms containing metabotypes characteristics and individual traits. Individuals in the control group receiving generic dietary advice based on national guidelines. The personalised approach resulted in higher dietary quality assessed by the Alternate Mediterranean Diet Score (effect size [95% CI], 0.77 [0.07, 1.48], 12% versus 3% increase) and significantly lower concentrations of triacylglycerol (-0.17 [-0.28, -0.06] log10 mmol/L), total cholesterol (-0.42 [-0.74, -0.10] mmol/L), LDL-cholesterol (-0.34, [-0.60, -0.09] mmol/L) and lower triacylglycerol-glucose index (-0.40, [-0.67, -0.13]). Sixteen phosphatidylcholines and six lysophosphatidylcholines, predominately with chain lengths of 30-36 carbons were lower in the personalised group.CONCLUSIONS: Personalised nutrition advice delivered using the metabotype framework is effective to improve dietary quality, which could result in reduced CVD risk, and metabolic heath biomarkers. This article is protected by copyright. All rights reserved.PMID:37038841 | DOI:10.1002/mnfr.202200620

Curr Drug Metab. 2023 Apr 6. doi: 10.2174/1389200224666230406114012. Online ahead of print.ABSTRACTBACKGROUND: Polygonatum sibiricum polysaccharide (PSP) can improve insulin resistance and inhibit oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined.METHODS: In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses.RESULTS: Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the Firmicutes/Bacteroidetes ratio in the gut. At the genus level, PSP treatment increased the relative abundances of Blautia, Adlercreutzia, Akkermansia and Parabacteroides while decreasing Prevotella, Megamonas funiformis and Escherichia. Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine, (±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, D-mannose 6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol, UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation of Prevotella, Megamonas funiformis, Escherichia, Blautia and Adlercreutzia.CONCLUSION: Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM. The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.PMID:37038712 | DOI:10.2174/1389200224666230406114012

Hemasphere. 2023 Apr 5;7(4):e858. doi: 10.1097/HS9.0000000000000858. eCollection 2023 Apr.ABSTRACTEarly fever after chimeric antigen receptor T-cell (CAR-T) therapy can reflect both an infection or cytokine release syndrome (CRS). Identifying early infections in the setting of CRS and neutropenia represents an unresolved clinical challenge. In this retrospective observational analysis, early fever events (day 0-30) were characterized as infection versus CRS in 62 patients treated with standard-of-care CD19.CAR-T for relapsed/refractory B-cell non-Hodgkin lymphoma. Routine serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], procalcitonin [PCT]) were recorded daily. Exploratory plasma proteomics were performed longitudinally in 52 patients using a multiplex proximity extension assay (Olink proteomics). Compared with the CRSonly cohort, we noted increased event-day IL-6 (median 2243 versus 64 pg/mL, P = 0.03) and particularly high PCT levels (median 1.6 versus 0.3 µg/L, P < 0.0001) in the patients that developed severe infections. For PCT, an optimal discriminatory threshold of 1.5 µg/L was established (area under the receiver operating characteristic curve [AUCROC] = 0.78). Next, we incorporated day-of-fever PCT levels with the patient-individual CAR-HEMATOTOX score. In a multicenter validation cohort (n = 125), we confirmed the discriminatory capacity of this so-called HT10 score for early infections at first fever (AUCROC = 0.87, P < 0.0001, sens. 86%, spec. 86%). Additionally, Olink proteomics revealed pronounced immune dysregulation and endothelial dysfunction in patients with severe infections as evidenced by an increased ANGPT2/1 ratio and an altered CD40/CD40L-axis. In conclusion, the high discriminatory capacity of the HT10 score for infections highlights the advantage of dynamic risk assessment and supports the incorporation of PCT into routine inflammatory panels. Candidate markers from Olink proteomics may further refine risk-stratification. If validated prospectively, the score will enable risk-adapted decisions on antibiotic use.PMID:37038465 | PMC:PMC10082278 | DOI:10.1097/HS9.0000000000000858