PubMed

Metabolomics. 2023 Sep 30;19(10):86. doi: 10.1007/s11306-023-02053-3.ABSTRACTINTRODUCTION: Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS).OBJECTIVES: To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN.METHODS: We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification.RESULTS: Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN.CONCLUSION: This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core.PMID:37776501 | DOI:10.1007/s11306-023-02053-3

Microsc Res Tech. 2023 Sep 29. doi: 10.1002/jemt.24429. Online ahead of print.ABSTRACTDicleptera chinensis J. (Acanthaceae) has been employed in traditional medicinal systems for treating various ailments. It has been used as an anti-inflammatory, wound healing, diuretic, and detoxifying agent in different regions of the world. This study determines several pharmacognostic standards, which are useful to ensure safety, efficacy, and purity of D. chinensis. Different parts of the plant were examined through a scanning electron microscope and light microscope, and cross-section images revealed several useful botanical features of the plant. The color, size, odor, shape, and surface characteristics of plant parts were also examined macroscopically. Pharmacognostic standardization parameters including ash values, loss on drying, swelling index, hemolytic index, and foaming index were determined in accordance with WHO guidelines. Heavy metal analysis was executed through atomic absorption spectrophotometer which depicted the presence of heavy metals and trace elements within the acceptable range. Qualitative phytochemical tests for alkaloids, flavonoids, saponins, glycosides, tannins, carbohydrates, lipids, protein, and so forth of plant extract were also performed, which showed the valuable amount of these phytochemicals useful for medicinal purposes. Preliminary phytochemical tests provide an indication for major phytoconstituents classes present in the plant. These quantitative and qualitative microscopic features are helpful in establishing the pharmacopeia standards of plant. Assessment of various pharmacognostic features such as morphology of various plant parts explained along with physicochemical and phytochemical analysis could be very helpful for future research. RESEARCH HIGHLIGHTS: Pharmacognostic standardization is employed as reported evidence for correct identification of D. chinensis. Structures identified by scanning electron microscopy and light microscopy serve as diagnostic features of plant. Important secondary metabolites present in the plant suggest the need for further exploration through advanced metabolomics and other analytical techniques.PMID:37775982 | DOI:10.1002/jemt.24429

Pharmacotherapy. 2023 Sep 29. doi: 10.1002/phar.2882. Online ahead of print.ABSTRACTBACKGROUND: Levocarnitine (L-carnitine) has shown promise as a metabolic-therapeutic for septic shock, where mortality approaches 40%. However, high-dose (≥ 6 grams) intravenous supplementation results in a broad range of serum concentrations.OBJECTIVES: We sought to describe the population pharmacokinetics (PK) of high-dose L-carnitine, test various estimates of kidney function, and assess the correlation of PK parameters with pre-treatment metabolites in describing drug response for patients with septic shock.METHODS: We leveraged serum samples and metabolomics data from a phase II trial of L-carnitine in vasopressor-dependent septic shock. Patients were adaptively randomized to receive intravenous L-carnitine (6 grams, 12 grams, or 18 grams) or placebo. Serum was collected at baseline (T0); end-of-infusion (T12); and 24, 48, and 72 hours after treatment initiation. Population PK analysis was done with baseline normalized concentrations using nonlinear mixed effect models in the modeling platform Monolix. Various estimates of kidney function, patient demographics, dose received, and organ dysfunction were tested as population covariates.RESULTS: The final dataset included 542 serum samples from 130 patients randomized to L-carnitine. A two-compartment model with linear elimination and a fixed volume of distribution (17.1 liters) best described the data and served as a base structural model. Kidney function estimates as a covariate on the elimination rate constant (k) reliably improved model fit. Estimated glomerular filtration rate (eGFR), based on the 2021 Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation with creatinine and cystatin C, outperformed creatinine clearance (Cockcroft-Gault) and older CKD-EPI equations that use an adjustment for self-identified race.CONCLUSIONS: High-dose L-carnitine supplementation is well-described by a two-compartment population PK model in patients with septic shock. Kidney function estimates that leverage cystatin C provided superior model fit. Future investigations into high-dose L-carnitine supplementation should consider baseline metabolic status and dose adjustments based on renal function over a fixed or weight-based dosing paradigm.PMID:37775945 | DOI:10.1002/phar.2882

Cardiovasc Diabetol. 2023 Sep 29;22(1):262. doi: 10.1186/s12933-023-01994-2.ABSTRACTBACKGROUND: Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet.METHODS: PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes.RESULTS: Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results.CONCLUSIONS: Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.PMID:37775736 | DOI:10.1186/s12933-023-01994-2

ISME J. 2023 Sep 29. doi: 10.1038/s41396-023-01522-w. Online ahead of print.ABSTRACTNitrogen is a limiting nutrient for degraders function in hydrocarbon-contaminated environments. Biological nitrogen fixation by diazotrophs is a natural solution for supplying bioavailable nitrogen. Here, we determined whether the diazotroph Azotobacter chroococcum HN can provide nitrogen to the polycyclic aromatic hydrocarbon-degrading bacterium Paracoccus aminovorans HPD-2 and further explored the synergistic interactions that facilitate pyrene degradation in nitrogen-deprived environments. We found that A. chroococcum HN and P. aminovorans HPD-2 grew and degraded pyrene more quickly in co-culture than in monoculture. Surface-enhanced Raman spectroscopy combined with 15N stable isotope probing (SERS - 15N SIP) demonstrated that A. chroococcum HN provided nitrogen to P. aminovorans HPD-2. Metabolite analysis and feeding experiments confirmed that cross-feeding occurred between A. chroococcum HN and P. aminovorans HPD-2 during pyrene degradation. Transcriptomic and metabolomic analyses further revealed that co-culture significantly upregulated key pathways such as nitrogen fixation, aromatic compound degradation, protein export, and the TCA cycle in A. chroococcum HN and quorum sensing, aromatic compound degradation and ABC transporters in P. aminovorans HPD-2. Phenotypic and fluorescence in situ hybridization (FISH) assays demonstrated that A. chroococcum HN produced large amounts of biofilm and was located at the bottom of the biofilm in co-culture, whereas P. aminovorans HPD-2 attached to the surface layer and formed a bridge-like structure with A. chroococcum HN. This study demonstrates that distinct syntrophic interactions occur between A. chroococcum HN and P. aminovorans HPD-2 and provides support for their combined use in organic pollutant degradation in nitrogen-deprived environments.PMID:37775536 | DOI:10.1038/s41396-023-01522-w

Lancet Digit Health. 2023 Oct;5(10):e712-e736. doi: 10.1016/S2589-7500(23)00129-2.ABSTRACTData sharing is central to the rapid translation of research into advances in clinical medicine and public health practice. In the context of COVID-19, there has been a rush to share data marked by an explosion of population-specific and discipline-specific resources for collecting, curating, and disseminating participant-level data. We conducted a scoping review and cross-sectional survey to identify and describe COVID-19-related platforms and registries that harmonise and share participant-level clinical, omics (eg, genomic and metabolomic data), imaging data, and metadata. We assess how these initiatives map to the best practices for the ethical and equitable management of data and the findable, accessible, interoperable, and reusable (FAIR) principles for data resources. We review gaps and redundancies in COVID-19 data-sharing efforts and provide recommendations to build on existing synergies that align with frameworks for effective and equitable data reuse. We identified 44 COVID-19-related registries and 20 platforms from the scoping review. Data-sharing resources were concentrated in high-income countries and siloed by comorbidity, body system, and data type. Resources for harmonising and sharing clinical data were less likely to implement FAIR principles than those sharing omics or imaging data. Our findings are that more data sharing does not equate to better data sharing, and the semantic and technical interoperability of platforms and registries harmonising and sharing COVID-19-related participant-level data needs to improve to facilitate the global collaboration required to address the COVID-19 crisis.PMID:37775189 | DOI:10.1016/S2589-7500(23)00129-2

Ann Rheum Dis. 2023 Sep 29:ard-2022-223626. doi: 10.1136/ard-2022-223626. Online ahead of print.ABSTRACTOBJECTIVES: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.METHODS: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients.RESULTS: L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients.CONCLUSION: Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.PMID:37775153 | DOI:10.1136/ard-2022-223626

J Proteomics. 2023 Sep 27:105013. doi: 10.1016/j.jprot.2023.105013. Online ahead of print.ABSTRACTLaminaria digitata, a brown seaweed with prebiotic properties, can potentially enhance the resilience of weaned piglets to nutritional distress. However, their cell wall polysaccharides elude digestion by monogastric animals' endogenous enzymes. In vitro studies suggest alginate lyase's ability to degrade such polysaccharides. This study aimed to assess the impact of a 10% dietary inclusion of L. digitata and alginate lyase supplementation on the ileum proteome and metabolome, adopting a hypothesis-generating approach. Findings indicated that control piglets escalated glucose usage as an enteric energy source, as evidenced by the elevated abundance of PKLR and PCK2 proteins and decreased tissue glucose concentration. Additionally, the inclusion of seaweed fostered a rise in proteins linked to enhanced enterocyte structural integrity (ACTBL2, CRMP1, FLII, EML2 and MYLK), elevated peptidase activity (NAALADL1 and CAPNS1), and heightened anti-inflammatory activity (C3), underscoring improved intestinal function. In addition, seaweed-fed piglets showed a reduced abundance of proteins related to apoptosis (ERN2) and proteolysis (DPP4). Alginate lyase supplementation appeared to amplify the initial effects of seaweed-only feeding, by boosting the number of differential proteins within the same pathways. This amplification is potentially due to increased intracellular nutrient availability, making a compelling case for further exploration of this dietary approach. SIGNIFICANCE: Pig production used to rely heavily on antibiotics and zinc oxide to deal with post-weaning stress in a cost-effective way. Their negative repercussions on public health and the environment have motivated heavy restrictions, and a consequent search for alternative feed ingredients/supplements. One such alternative is Laminaria digitata, a brown seaweed whose prebiotic components can help weaned piglets deal with nutritional stress, by improving their gut health and immune status. However, their recalcitrant cell walls have antinutritional properties, for which alginate lyase supplementation is a possible solution. By evaluating ileal metabolism as influenced by dietary seaweed and enzyme supplementation, we aim at discovering how the weaned piglet adapts to them and what are their effects on this important segment of the digestive system.PMID:37775079 | DOI:10.1016/j.jprot.2023.105013

Pharmacol Res. 2023 Sep 27:106941. doi: 10.1016/j.phrs.2023.106941. Online ahead of print.ABSTRACTSolute carrier (SLC) transport proteins are fundamental for the translocation of endogenous compounds and drugs across membranes, thus playing a critical role in disease susceptibility and drug response. Because only a limited number of transporter substrates are currently known, the function of a large number of SLC transporters is elusive. Here, we describe the proof-of-concept of a novel strategy to identify SLC transporter substrates exemplarily for the proton-coupled peptide transporter (PEPT) 2 (SLC15A2) and multidrug and toxin extrusion (MATE) 1 transporter (SLC47A1), which are important renal transporters of drug reabsorption and excretion, respectively. By combining metabolomic profiling of mice with genetically-disrupted transporters, in silico ligand screening and in vitro transport studies for experimental validation, we identified nucleobases and nucleoside-derived anticancer and antiviral agents (flucytosine, cytarabine, gemcitabine, capecitabine) as novel drug substrates of the MATE1 transporter. Our data confirms the successful applicability of this new approach for the identification of transporter substrates in general, which may prove particularly relevant in drug research.PMID:37775020 | DOI:10.1016/j.phrs.2023.106941

Fish Shellfish Immunol. 2023 Sep 27:109118. doi: 10.1016/j.fsi.2023.109118. Online ahead of print.ABSTRACTSpecies in Triplophysa display strong adaptability to the extreme environment of the plateau, thus offering an ideal model to study the molecular mechanism of fish adaptation to environmental stress. In the present study, we conducted integrated analysis of the transcriptome and metabolism of liver tissue in Triplophysa siluroides under heat stress (28 °C) and control (10 °C) conditions to identify heat stress-induced genes, metabolites and pathways. RNA-Seq identified 2373 differentially expressed genes, which consisted of 1360 upregulated genes and 1013 downregulated genes, in the heat stress group vs. the control group. Genes in the heat shock protein (Hsp) family, including Hsp40, Hsp70, Hsp90 and other Hsps, were strongly upregulated by heat stress. Pathway enrichment analysis revealed that the PI3K/AKT/mTOR and protein processing in the endoplasmic reticulum (ER) pathways were significantly affected by heat stress. Metabolism sequencing identified a total of 155 differentially abundant metabolites, including 118 significantly upregulated metabolites and 37 downregulated metabolites. Combined analysis of the transcriptome and metabolism results showed that ubiquitin-dependent proteolysis and purine metabolism pathways were enhanced in response to acute heat stress to protect cells from damage under stress conditions. The results of this study may contribute to our understanding of the underlying molecular mechanism of the heat stress response in cold-water fish.PMID:37774901 | DOI:10.1016/j.fsi.2023.109118

J Proteome Res. 2023 Sep 29. doi: 10.1021/acs.jproteome.3c00488. Online ahead of print.ABSTRACTBlood serum and plasma are arguably the most commonly analyzed clinical samples, with dozens of proteins serving as validated biomarkers for various human diseases. Top-down proteomics may provide additional insights into disease etiopathogenesis since this approach focuses on protein forms, or proteoforms, originally circulating in blood, potentially providing access to information about relevant post-translational modifications, truncations, single amino acid substitutions, and many other sources of protein variation. However, the vast majority of proteomic studies on serum and plasma are carried out using peptide-centric, bottom-up approaches that cannot recapitulate the original proteoform content of samples. Clinical laboratories have been slow to adopt top-down analysis, also due to higher sample handling requirements. In this study, we describe a straightforward protocol for intact proteoform sample preparation based on the depletion of albumin and immunoglobulins, followed by simplified protein fractionation via polyacrylamide gel electrophoresis. After molecular weight-based fractionation, we supplemented the traditional liquid chromatography-tandem mass spectrometry (LC-MS2) data acquisition with high-field asymmetric waveform ion mobility spectrometry (FAIMS) to further simplify serum proteoform mixtures. This LC-FAIMS-MS2 method led to the identification of over 1000 serum proteoforms < 30 kDa, outperforming traditional LC-MS2 data acquisition and more than doubling the number of proteoforms identified in previous studies.PMID:37774690 | DOI:10.1021/acs.jproteome.3c00488

Food Chem. 2023 Aug 26;434:137277. doi: 10.1016/j.foodchem.2023.137277. Online ahead of print.ABSTRACTThe flavor of Pacific oyster (Crassostrea gigas) significantly changed during the depuration process. This work aimed to explore the mechanism of flavor changes during the 72 h depuration by metabolomics combined with gas chromatography-ion mobility spectrometry (GC-IMS). The metabolomics analysis indicated that carbohydrate metabolism was more affected in the early stage of depuration, including the citrate cycle, glyoxylae and dicarboxylate metabolism, etc. After 72 h depuration, it affected mainly the metabolism of global and overview maps and nucleoside metabolism, etc. The equivalent umami concentration (EUC) value was calculated and exhibited a gradual increase following a 48 h depuration. The GC-MS results revealed that the content of furans was the highest, and the content of aldehydes, ketones, and alcohols was the lowest after 48 h depuration, while the content of aldehydes, ketones, and alcohols increased after 72 h depuration. All these results suggested the depuration period was recommended to be controlled within 48 h.PMID:37774638 | DOI:10.1016/j.foodchem.2023.137277

Int J Food Microbiol. 2023 Sep 24;407:110417. doi: 10.1016/j.ijfoodmicro.2023.110417. Online ahead of print.ABSTRACTGrep-chhurpi, peha, peron namsing and peruñyaan are lesser-known home-made fermented soybean foods prepared by the native people of Arunachal Pradesh in India. Present work aims to study the microbiome, their functional annotations, metabolites and recovery of metagenome-assembled genomes (MAGs) in these four fermented soybean foods. Metagenomes revealed the dominance of bacteria (97.80 %) with minor traces of viruses, eukaryotes and archaea. Bacillota is the most abundant phylum with Bacillus subtilis as the abundant species. Metagenome also revealed the abundance of lactic acid bacteria such as Enterococcus casseliflavus, Enterococcus faecium, Mammaliicoccus sciuri and Staphylococcus saprophyticus in all samples. B. subtilis was the major species found in all products. Predictive metabolic pathways showed the abundance of genes associated with metabolisms. Metabolomics analysis revealed both targeted and untargeted metabolites, which suggested their role in flavour development and therapeutic properties. High-quality MAGs, identified as B. subtilis, Enterococcus faecalis, Pediococcus acidilactici and B. velezensis, showed the presence of several biomarkers corresponding to various bio-functional properties. Gene clusters of secondary metabolites (antimicrobial peptides) and CRISPR-Cas systems were detected in all MAGs. This present work also provides key elements related to the cultivability of identified species of MAGs for future use as starter cultures in fermented soybean food product development. Additionally, comparison of microbiome and metabolites of grep-chhurpi, peron namsing and peruñyaan with that of other fermented soybean foods of Asia revealed a distinct difference.PMID:37774634 | DOI:10.1016/j.ijfoodmicro.2023.110417

Food Chem. 2023 Sep 21;435:137531. doi: 10.1016/j.foodchem.2023.137531. Online ahead of print.ABSTRACTMeat authenticity addresses parameters such as species, breed, sex, housing system and postmortem treatment. Seventy-four beef backs from two breeds ('Fleckvieh' and 'Schwarzbunt') and three cattle types (heifer, cow, young bull) were dry-aged and wet-aged up to 28 days and analyzed by 1H NMR spectroscopy. Statistical models based on partial least squares regression and discriminant analysis were performed to classify the beef samples by breed, cattle type, aging time, and aging type based on their 1H NMR spectra. The aging time of beef samples can be predicted with an error ± 2.28 days. The cattle type model has an accuracy of cross-validation of 99.2 %, the breed models of 100 % and the aging type model for 28-days aged samples of 99.6 %. These models allow the authentication of beef samples in terms of breed, cattle type, aging time, and aging type with a single 1H NMR measurement.PMID:37774627 | DOI:10.1016/j.foodchem.2023.137531

Food Chem. 2023 Sep 23;435:137570. doi: 10.1016/j.foodchem.2023.137570. Online ahead of print.ABSTRACTThis study aimed to examine the effects of sterilization methods on the degradation ability and bioactive compound production of Irpex lacteus in wheat straw. Following 28 days of fermentation, the lignin content of samples autoclaved and pasteurized at pH 4.5 was reduced by 16.0 % - 21.7 % compared to pasteurized samples without pH adjustment, accompanied by a significant increase in sugar yield ranging from 83.30 % - 96.35 %. Autoclaved samples exhibited the lowest total phenol content and antioxidant activity (P < 0.05). Bacillus occupied an absolute advantage (89.1 %) in samples pasteurized at pH 4.5, whereas 10 bacterial genera exhibited abundances above 1 % in pasteurized samples without pH adjustment. Furthermore, 45.1 % - 47.2 % of the metabolites comprised lipids and lipid-like molecules, and some of them were improved by pasteurization at pH 4.5. Overall, pasteurization at acidic conditions is an effective sterilization method for the fungal conversion of wheat straw.PMID:37774616 | DOI:10.1016/j.foodchem.2023.137570

Ann Med. 2023;55(2):2261477. doi: 10.1080/07853890.2023.2261477. Epub 2023 Sep 29.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with gut microbiota dysbiosis; however, its etiology remains unclear. MicroRNA (miRNA)-microbiome interactions play an essential role in host health and disease.METHODS: To investigate the gut microbiome and host miRNA profiles in colitis, we used a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis (UC) model. Metagenomic sequencing and metabolome profiling were performed to explore typical microbiota and metabolite signatures in colitis, whereas mRNA and miRNA sequencing were used to determine differentially expressed miRNAs and their target genes in the inflamed colon.RESULTS: A total of 986 miRNAs were identified between the two groups, with 41 upregulated and 21 downregulated miRNAs in colitis mice compared to the control group. Notably, the target genes of these significantly altered miRNAs were primarily enriched in the immune and inflammation-related pathways. Second, LEfSe analysis revealed bacterial biomarkers distinguishing the two groups, with significantly higher levels of commonly encountered pathogens such as Escherichia coli and Shigella flexneri in the UC group, whereas beneficial species such as Bifidobacterium pseudolongum were more abundant in the control group. Microbiota metabolites histamine, N-acetylhistamine, and glycocholic acid were found to be downregulated in colitis mice. Spearman correlation further revealed the potential crosstalk between the microbiota profile and colonic miRNA, revealing the possibility of microbiome-miRNA interactions involved in IBD development.CONCLUSIONS: Our data reveal the relationships between multi-omic features during UC and suggest that targeting specific miRNAs may provide new avenues for the development of effective miRNA-based therapeutics.PMID:37774039 | DOI:10.1080/07853890.2023.2261477

Commun Med (Lond). 2023 Sep 29;3(1):128. doi: 10.1038/s43856-023-00355-0.ABSTRACTBACKGROUND: Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality.METHODS: A case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP).RESULTS: The fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality.CONCLUSIONS: Intestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM.PMID:37773543 | DOI:10.1038/s43856-023-00355-0

Support Care Cancer. 2023 Sep 29;31(10):601. doi: 10.1007/s00520-023-08074-x.ABSTRACTThe causes of variation in toxicity to the same treatment regimen among seemingly similar patients remain largely unknown. There was tremendous optimism that the patient's germline genome would be strongly predictive of treatment-related toxicity and could be used to personalize treatment and improve therapeutic outcomes. However, there has been limited success in discovering robust pharmacogenetic predictors of treatment-related toxicity and even less progress in translating the few validated predictors into clinical practice. It is apparent that identification of toxicity predictors that can be used to predict and prevent treatment-related toxicity will require thinking beyond germline genomics. To that end, we propose an integrated biomarker discovery approach that recognizes that a patient's toxicity risk is determined by the cumulative effects of a broad range of "omic" and non-omic factors. This commentary describes the limited success in discovering and translating clinical and pharmacogenetic toxicity predictors into clinical practice. We illustrate the evolution of cancer toxicity biomarker discovery and translation through studies of taxane-induced peripheral neuropathy, which is one of the most common and debilitating side effects of cancer treatment. We then discuss the opportunities for discovering non-genomic (e.g., metabolomic, lipidomic, transcriptomic, proteomic, microbiomic, medical, behavioral, environmental) and integrated biomarkers that may be more strongly predictive of toxicity risk and the potential challenges with translating integrated biomarkers into clinical practice. This integrated biomarker discovery approach may circumvent some of the major limitations in toxicity biomarker science and move precision oncology treatment forward so that patients receive maximum treatment benefit with minimal toxicity.PMID:37773300 | DOI:10.1007/s00520-023-08074-x

Sci Rep. 2023 Sep 29;13(1):16372. doi: 10.1038/s41598-023-43466-3.ABSTRACTGreen glutinous rice is a unique genetic germplasm that has yet to be adequately studied. This study investigated antioxidant capacity and flavonoid metabolites in the bran layer of green glutinous rice (LvH) compared to purple (HeiH), red (HongH) and white (GJG) varieties. The results showed that LvH bran had significantly higher content of total flavonoids and anthocyanin than that of HongH (1.91-fold and 4.34-fold) and GJG (2.45-fold and 13.30-fold). LvH bran also showed significantly higher levels of vitamin B1 and vitamin E than that of HeiH (1.94-fold and 1.15-fold) and HongH (1.22-fold and 1.13-fold), indicating that green glutinous rice bran was rich in bioactive components. LvH bran showed significantly lower IC50 values for scavenging DPPH and ATBS radicals than GJG and even significantly lower IC50 value for scavenging DPPH radicals than HongH, highlighting its potential as an effective source of antioxidants. LvH bran had significantly different downstream metabolite synthesis in the flavonoid pathway compared to HeiH, HongH, and GJG, with 40, 26, and 22 different metabolites, 23, 20, and 33 up-regulated differentially expressed metabolites (DEMs), and 73, 50, and 13 down-regulated DEMs, respectively. Of the 139 flavonoid metabolites identified in colored rice bran, 26 metabolites showed significant positive correlation with both ABTS and DPPH radical scavenging capacity. Typically, quercetin derivatives showed potential for evaluating the antioxidant capacity of colored rice bran. These findings offer valuable insights into the antioxidant properties of green glutinous rice bran and provide references for better understanding of flavonoid metabolites in different colored rice bran.PMID:37773271 | DOI:10.1038/s41598-023-43466-3

Microbiome. 2023 Sep 29;11(1):215. doi: 10.1186/s40168-023-01652-5.ABSTRACTBACKGROUND: The increased growth rate of young animals can lead to higher lactation performance in adult goats; however, the effects of the ruminal microbiome on the growth of young goats, and the contribution of the early-life rumen microbiome to lifelong growth and lactation performance in goats has not yet been well defined. Hence, this study assessed the rumen microbiome in young goats with different average daily gains (ADG) and evaluated its contribution to growth and lactation performance during the first lactation period.RESULTS: Based on monitoring of a cohort of 99 goats from youth to first lactation, the 15 highest ADG (HADG) goats and 15 lowest ADG (LADG) goats were subjected to rumen fluid microbiome and metabolome profiling. The comparison of the rumen metagenome of HADG and LADG goats revealed that ruminal carbohydrate metabolism and amino acid metabolism function were enhanced in HADG goats, suggesting that the rumen fluid microbiome of HADG goats has higher feed fermentation ability. Co-occurrence network and correlation analysis revealed that Streptococcus, Candidatus Saccharimonans, and Succinivibrionaceae UCG-001 were significantly positively correlated with young goats' growth rates and some HADG-enriched carbohydrate and protein metabolites, such as propionate, butyrate, maltoriose, and amino acids, while several genera and species of Prevotella and Methanogens exhibited a negative relationship with young goats' growth rates and correlated with LADG-enriched metabolites, such as rumen acetate as well as methane. Additionally, some functional keystone bacterial taxa, such as Prevotella, in the rumen of young goats were significantly correlated with the same taxa in the rumen of adult lactation goats. Prevotella also enriched the rumen of LADG lactating goats and had a negative effect on rumen fermentation efficiency in lactating goats. Additional analysis using random forest machine learning showed that rumen fluid microbiota and their metabolites of young goats, such as Prevotellaceae UCG-003, acetate to propionate ratio could be potential microbial markers that can potentially classify high or low ADG goats with an accuracy of prediction of > 81.3%. Similarly, the abundance of Streptococcus in the rumen of young goats could be predictive of milk yield in adult goats with high accuracy (area under the curve 91.7%).CONCLUSIONS: This study identified the keystone bacterial taxa that influence carbohydrate and amino acid metabolic functions and shape the rumen fluid microbiota in the rumen of adult animals. Keystone bacteria and their effects on rumen fluid microbiota and metabolome composition during early life can lead to higher lactation performance in adult ruminants. These findings suggest that the rumen microbiome together with their metabolites in young ruminants have long-term effect on feed efficiency and animal performance. The fundamental knowledge may allow us to develop advanced methods to manipulate the rumen microbiome and improve production efficiency of ruminants. Video Abstract.PMID:37773207 | DOI:10.1186/s40168-023-01652-5