PubMed

Seizure. 2023 Mar 16;107:52-59. doi: 10.1016/j.seizure.2023.03.014. Online ahead of print.ABSTRACTOBJECTIVE: The ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a subset of patients with drug-resistant epilepsy, although the mechanisms of the KD have not been fully elucidated. The aims of this observational study were to investigate comprehensive short-term metabolic changes induced by the KD and to explore candidate metabolites or pathways for potential new therapeutic targets.METHODS: Subjects included patients with intractable epilepsy who had undergone the KD therapy (the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil). Plasma and urine samples were obtained before and at 2-4 weeks after initiation of the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS).RESULTS: Samples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively. The KD increased ketone bodies, various fatty acids, lipids, and their conjugates. In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA, including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric acid and lactic acid, were elevated.CONCLUSIONS: The metabolites that were significantly changed after the initiation of the KD and related metabolites may be candidates for further studies for neuronal actions to develop new anti-seizure medications.PMID:36958064 | DOI:10.1016/j.seizure.2023.03.014

PLoS One. 2023 Mar 23;18(3):e0283389. doi: 10.1371/journal.pone.0283389. eCollection 2023.ABSTRACTWith the increasing incidence and mortality of chronic kidney disease (CKD), targeted therapies for CKD have been explored constantly. The important role of gut microbiota on CKD has been emphasized increasingly, it is necessary to analyze the metabolic mechanism of CKD patients from the perspective of gut microbiota. In this study, bioinformatics was used to analyze the changes of gut microbiota between CKD and healthy control (HC) groups using 315 samples from NCBI database. Diversity analysis showed significant changes in evenness compared to the HC group. PCoA analysis revealed significant differences between the two groups at phylum level. In addition, the F/B ratio was higher in CKD group than in HC group, suggesting the disorder of gut microbiota, imbalance of energy absorption and the occurrence of metabolic syndrome in CKD group. The study found that compared with HC group, the abundance of bacteria associated with impaired kidney was increased in CKD group, such as Ralstonia and Porphyromonas, which were negatively associated with eGFR. PICRUSt2 was used to predict related functions and found that different pathways between the two groups were mainly related to metabolism, involving the metabolism of exogenous and endogenous substances, as well as Glycerophospholipid metabolism, which provided evidence for exploring the relationship between gut microbiota and lipid metabolism. Therefore, in subsequent studies, special attention should be paid to these bacteria and metabolic pathway, and animal experiments and metabolomics studies should be conducted explore the association between bacterial community and CKD, as well as the therapeutic effects of these microbial populations on CKD.PMID:36952529 | DOI:10.1371/journal.pone.0283389

J Am Chem Soc. 2023 Mar 23. doi: 10.1021/jacs.3c00250. Online ahead of print.ABSTRACTSome members of the human gut microbiota profoundly influence their host's physiology, health, and therapeutic responses, but the responsible molecules and mechanisms are largely unknown. As part of a project to identify immunomodulators produced by gut microbes, we analyzed the metabolome of Collinsella aerofaciens, an actinomycete that figures prominently in numerous association studies. The associations are typically positive correlations of C. aerofaciens with pro-inflammatory responses and undesirable outcomes, but an association with favorable responses to PD-1/PD-L1 cancer immunotherapy is a notable exception. A phenotypic assay-guided screen using dendritic cells (mBMDCs) and cytokine readouts identified the active compound, which was structurally characterized as a lysoglycoglycerolipid with an acetal-bearing β-galactofuranose head group (CaLGL-1, 1). The structural assignment was confirmed through total synthesis. Assays with tlr2-/-, tlr4-/-, and wt mBMDCs revealed TLR2-dependent signaling. CaLGL-1 is produced by a conversion of a bacterially biosynthesized plasmalogen (CaPlsM, 3) to CaLGL-1 (1) in a low-pH environment.PMID:36952265 | DOI:10.1021/jacs.3c00250

Shock. 2023 Mar 24. doi: 10.1097/SHK.0000000000002117. Online ahead of print.ABSTRACTBACKGROUND: The gut plays an important role in the development of sepsis and acts as one of the possible drivers of multiple organ dysfunction syndrome (MODS). This study aimed to explore the dynamic alterations in the gut microbiota and its metabolites in septic patients at different stages of ICU admission.METHODS: In this prospective observational study, a total of 109 fecal samples from 23 septic patients, 16 non-septic ICU patients and 10 healthy controls were analyzed. 16S rRNA gene sequencing and UPLC-MS/MS targeted metabolomics were used for microbiota and metabolome analysis. A prediction model combining the SOFA score, Klebsiella, taurocholic acid, and butyric acid was used to predict the prognosis of sepsis.RESULTS: The diversity and dominant species of the gut microbiota of septic patients were significantly disturbed. The proportions of normal gut microbiota, such as Firmicutes on the phylum level, as well as Faecalibacterium, Subdoligranulum, Ruminococcus, Agathobacter, and Blautia on the genus level, were decreased at different stages of ICU admission, while the proportions of potential pathogenic bacteria, such as Proteobacteria on the phylum level, and Enterococcus and Stenotrophomonas on the genus level were significantly increased. In addition, the amount of short-chain fatty acids and secondary bile acids decreased in septic patients, while that of the primary bile acids increased markedly. Bacterial richness and diversity were lower in the non-surviving patients than those in the surviving patients in the later stage of ICU admission. In the nomogram model, the higher abundance of Klebsiella, concentration of taurocholic acid and SOFA score, combined with a lower butyric acid concentration, could predict a higher probability of death from sepsis.CONCLUSION: Our study indicated that the dynamical alterations of gut microbiota and its metabolites were associated with the prognosis of the sepsis. Based on these alterations and clinical indicators, a nomogram model to predict the prognosis of septic patients was performed.PMID:36951975 | DOI:10.1097/SHK.0000000000002117

Microbiol Spectr. 2023 Mar 23:e0455122. doi: 10.1128/spectrum.04551-22. Online ahead of print.ABSTRACTThe vast population of bacterial phages or viruses (virome) plays pivotal roles in the ecology of human microbial flora and health conditions. Obstacles, including poor viral sequence inference, strain-sensitive virus-host relationship, and the high diversity among individuals, hinder the in-depth understanding of the human virome. We conducted longitudinal studies of the virome based on constructing a high-quality personal reference metagenome (PRM). By applying long-read sequencing for representative samples, we could build a PRM of high continuity that allows accurate annotation and abundance estimation of viruses and bacterial species in all samples of the same individual by aligning short sequencing reads to the PRM. We applied this approach to a series of fecal samples collected for 6 months from a 2-year-old boy who had experienced a 2-month flare-up of atopic eczema (dermatitis) in this period. We identified 31 viral strains in the patient's gut microbiota and deciphered their strain-level relationship to their bacterial hosts. Among them, a lytic crAssphage developed into a dozen substrains and coordinated downregulation in the catabolism of aromatic amino acids (AAAs) in their host bacteria which govern the production of immune-active AAA derivates. The metabolic alterations confirmed based on metabolomic assays cooccurred with symptom remission. Our PRM-based analysis provides an easy approach for deciphering the dynamics of the strain-level human gut virome in the context of entire microbiota. Close temporal correlations among virome alteration, microbial metabolism, and disease remission suggest a potential mechanism for how bacterial phages in microbiota are intimately related to human health. IMPORTANCE The vast populations of viruses or bacteriophages in human gut flora remain mysterious. However, poor annotation and abundance estimation remain obstacles to strain-level analysis and clarification of their roles in microbiome ecology and metabolism associated with human health and diseases. We demonstrate that a personal reference metagenome (PRM)-based approach provides strain-level resolution for analyzing the gut microbiota-associated virome. When applying such an approach to longitudinal samples collected from a 2-year-old boy who has experienced a 2-month flare-up of atopic eczema, we observed thriving substrains of a lytic crAssphage, showing temporal correlation with downregulated catabolism of aromatic amino acids, lower production of immune-active metabolites, and remission of the disease. The PRM-based approach is practical and powerful for strain-centric analysis of the human gut virome, and the underlying mechanism of how strain-level virome dynamics affect disease deserves further investigation.PMID:36951555 | DOI:10.1128/spectrum.04551-22

Elife. 2023 Mar 23;12:e85289. doi: 10.7554/eLife.85289. Online ahead of print.ABSTRACTReactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacologic neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacologic suppression.PMID:36951533 | DOI:10.7554/eLife.85289

Xenobiotica. 2023 Mar 23:1-42. doi: 10.1080/00498254.2023.2194981. Online ahead of print.ABSTRACTDelta(9)-tetrahydrocannabinolic acid (THCA) and Delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterization and bioactivity of THCA and THCV remains elusive.To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of THC in these three systems, while THCV was transformed into THC and CBD.Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were sightly difference in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of BBB (blood-brain barrier) penetration compare to THCA.In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids.PMID:36951512 | DOI:10.1080/00498254.2023.2194981

Endocrinology. 2023 Mar 23:bqad053. doi: 10.1210/endocr/bqad053. Online ahead of print.NO ABSTRACTPMID:36951302 | DOI:10.1210/endocr/bqad053

Aging Cell. 2023 Mar 23:e13821. doi: 10.1111/acel.13821. Online ahead of print.ABSTRACTAging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial β-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.PMID:36951231 | DOI:10.1111/acel.13821

Physiol Plant. 2023 Mar 23:e13896. doi: 10.1111/ppl.13896. Online ahead of print.ABSTRACTSalt stress is a dominant environmental factor that restricts the growth and yield of crops. Nitrogen is an essential mineral element for plants, regulates various physiological and biochemical processes, and has been reported to enhance salt tolerance in plants. However, the crosstalk between salt and nitrogen in grapes is not well understood. In this study, we found that nitrogen supplementation (0.01 mol L-1 and 0.1 mol L-1 NH4 NO3 ) significantly increased the accumulation of proline, chlorophyll, Na+ , NH4 + and NO3 - , while it reduced the malondialdehyde content and inhibited photosynthetic performance under salt stress conditions (200 mmol L-1 NaCl). Further transcriptome and metabolome analyses showed that a total of 4890 differentially expressed genes (DEGs) and 753 differential accumulation metabolites (DAMs) were identified. Joint omics results revealed that plant hormone signal transduction pathway connected the DEGs and DAMs. In-depth analysis revealed that nitrogen supplementation increased the levels of endogenous abscisic acid (ABA), salicylic acid (SA) and jasmonic acid (JA) by inducing the expression of 11, 4 and 13 genes related to their respective biosynthesis pathway. In contrast, endogenous indoleacetic acid (IAA) content was significantly reduced due to the remarkable regulation of 7 genes of its biosynthetic pathway. The modulation in hormone contents subsequently activated the differential expression of 13, 10, 12 and 29 genes of the respective downstream hormone signaling transduction pathways. Overall, all results indicate that moderate nitrogen supplementation could improve salt tolerance by regulating grape physiology and endogenous hormone homeostasis, as well as the expression of key genes in signaling pathways, which provides new insights into the interactions between mineral elements and salt stress. This article is protected by copyright. All rights reserved.PMID:36951039 | DOI:10.1111/ppl.13896

Ecotoxicol Environ Saf. 2023 Apr 1;254:114737. doi: 10.1016/j.ecoenv.2023.114737. Epub 2023 Mar 10.ABSTRACTMicroplastic pollution is an emerging threat for marine and terrestrial ecosystems, which has raised global concerns about its implications for human health. Mounting evidence has shown that the gut microbiota plays a key role in human health and diseases. The gut bacteria could be disturbed by many environmental factors, including the microplastic particles. However, the size effect of polystyrene microplastics on mycobiome, as well as gut functional metagenome has not been well studied. In this study, we performed ITS sequencing to explore the size effect of polystyrene microplastics on the fungal composition, in combination with the shotgun metagenomics sequencing to reveal the size effects of polystyrene on the functional metagenome. We found that polystyrene microplastic particles with 0.05-0.1 µm diameter showed greater impact on the bacterial and fungal composition of gut microbiota as well as the metabolic pathways than the polystyrene microplastic particles with 9-10 µm diameter. Our results suggested that size-depended effects should not be ignored in the health risk assessment of microplastics.PMID:36950986 | DOI:10.1016/j.ecoenv.2023.114737

J Clin Endocrinol Metab. 2023 Mar 23:dgad168. doi: 10.1210/clinem/dgad168. Online ahead of print.ABSTRACTAIMS: Precision medicine has revolutionised our understanding of type 1 diabetes and neonatal diabetes, but has yet to improve insight into gestational diabetes (GDM), the most common obstetric complication, and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1h, 2h) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles.METHODS: 867 pregnant women with obesity (BMI > 30kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks' gestation (75g oral glucose tolerance test OGTT; WHO criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analysed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterised by HOMA2b and HOMA2s respectively.RESULTS: In women who developed GDM (n=241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics, and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycaemia had comparable insulin secretion and sensitivity to euglycaemic women potentially indicative of a novel mechanistic pathway.CONCLUSIONS: Patterns of glycaemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycaemia reflects a different mechanistic pathway for targeted management.PMID:36950879 | DOI:10.1210/clinem/dgad168

Data Brief. 2023 Mar 7;48:109038. doi: 10.1016/j.dib.2023.109038. eCollection 2023 Jun.ABSTRACTThe prawn Palaemon serratus exhibits a large distribution (occurring along the Northeastern Atlantic coast to the Mediterranean), and has thus been found suitable as model organism valuable for various ecotoxicological studies. However, little is still known about the potential input of its metabolome and particularly concerning a potential molecular sexual dimorphism observable in the different tissues of this organism. In an ecotoxicological point of view, inter-sex and inter-organ differences of the metabolomes may introduce analytical bias and impact the robustness of the analysis and its interpretation. To explore such possibilities, we obtained qualitative metabolomic data from the analysis of different organs of mature male and female Palaemon serratus. We used ultra-high-performance liquid chromatography-electrospray ionization-high resolution tandem mass spectrometry (UHPLC-ESI-HRMS on positive mode) to characterize the 75%-extracted metabolome of both gills, hepatopancreas, nervous gland, muscle and gonads. The data were dereplicated using specific metabolomic software (MetaboScape 4) and 2,782 features were extracted, 1,720 of them being also analysed on MS/MS mode, supporting molecular networking investigations with Metgem 1.3.6. These metabolites were thus putatively identified using GNPS (Global Natural Product Social) Molecular Networking databases for de-novo annotation followed by manual curation of 84 metabolites. This data provides essential information on the important sexual dimorphism occurring at the molecular level in the different organs and supports further research on physiology and ecotoxicology in common European prawn.PMID:36950560 | PMC:PMC10027497 | DOI:10.1016/j.dib.2023.109038

Front Mol Biosci. 2023 Mar 6;10:1074263. doi: 10.3389/fmolb.2023.1074263. eCollection 2023.ABSTRACTIn the present study, the development and optimization of a thin film solid phase microextraction method (TF-SPME) was conducted for metabolomics profiling of eight steroid compounds (androsterone, dihydrotestosterone, dihydroepiandrosterone, estradiol, hydroxyprogesterone, pregnenolone, progesterone and testosterone) from urine samples. For optimization of extraction method, two extraction sorbents (PAN-C18 and PS-DVB) were used as they are known to be effective for isolation of low-polarity analytes. The stages of sample extraction and analyte desorption were considered as the most crucial steps in the process. Regarding the selection of the most suitable desorption solution, six different mixtures were analyzed. As a result, the mixture of ACN: MeOH (1:1, v/v) was chosen in terms of the highest analytes' abundances that were achieved using the chosen solvent. Besides other factors were examined such as the volume of desorption solvent and the time of both extraction and desorption processes. The analytical determination was carried out using the ultra-high performance liquid chromatography coupled with high resolution tandem mass spectrometry detection in electrospray ionization and positive polarity in a scan mode (UHPLC-ESI-QTOF/MS). The developed and optimized TF-SPME method was validated in terms of such parameters as extraction efficiency, recovery as well as matrix effect. As a result, the extraction efficiency and recovery were in a range from 79.3% to 99.2% and from 88.8% to 111.8%, respectively. Matrix effect, calculated as coefficient of variation was less than 15% and was in a range from 1.4% to 11.1%. The values of both validation parameters (recovery and matrix effect) were acceptable in terms of EMA criteria. The proposed TF-SPME method was used successfully for isolation of steroids hormones from pooled urine samples before and after enzymatic hydrolysis of analytes.PMID:36950525 | PMC:PMC10025495 | DOI:10.3389/fmolb.2023.1074263

J Clin Exp Hepatol. 2023 Mar-Apr;13(2):203-217. doi: 10.1016/j.jceh.2022.11.012. Epub 2022 Nov 26.ABSTRACTBACKGROUND/AIMS: Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population has previously identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid, and purine metabolism. However, the detection of thousands of analytes by LC-MS in a biological sample in a single experiment potentially introduces false discovery errors. To verify these observed metabolic perturbations, a second validation dataset from the same population was profiled in a similar fashion.METHODS: Reverse-phase ultra-performance liquid-chromatography mass spectrometry was utilised to acquire the global spectral profile of 98 spot urine samples (from 46 healthy volunteers and 52 CCA patients) recruited from Khon Kaen, northeast Thailand (the highest incidence of CCA globally).RESULTS: Metabolites were differentially expressed in the urinary profiles from CCA patients. High urinary elimination of bile acids was affected by the presence of obstructive jaundice. The urine metabolome associated with non-jaundiced CCA patients showed a distinctive pattern, similar but not identical to published studies. A panel of 10 metabolites achieved a diagnostic accuracy of 93.4% and area under the curve value of 98.8% (CI = 96.3%-100%) for the presence of CCA.CONCLUSIONS: Global characterisation of the CCA urinary metabolome identified several metabolites of biological interest in this validation study. Analyses of the diagnostic utility of the discriminant metabolites showed excellent diagnostic potential. Further larger scale studies are required to confirm these findings internationally, particularly in comparison to sporadic CCA, not associated with liver fluke infestation.PMID:36950498 | PMC:PMC10025591 | DOI:10.1016/j.jceh.2022.11.012

Front Plant Sci. 2023 Mar 6;14:1123655. doi: 10.3389/fpls.2023.1123655. eCollection 2023.ABSTRACTMicronutrient malnutrition is a serious threat to the developing world's human population, which largely relies on a cereal-based diet that lacks diversity and micronutrients. Besides major cereals, millets represent the key sources of energy, protein, vitamins, and minerals for people residing in the dryland tropics and drought-prone areas of South Asia and sub-Saharan Africa. Millets serve as multi-purpose crops with several salient traits including tolerance to abiotic stresses, adaptation to diverse agro-ecologies, higher productivity in nutrient-poor soils, and rich nutritional characteristics. Considering the potential of millets in empowering smallholder farmers, adapting to changing climate, and transforming agrifood systems, the year 2023 has been declared by the United Nations as the International Year of Millets. In this review, we highlight recent genetic and genomic innovations that can be explored to enhance grain micronutrient density in millets. We summarize the advances made in high-throughput phenotyping to accurately measure grain micronutrient content in cereals. We shed light on genetic diversity in millet germplasm collections existing globally that can be exploited for developing nutrient-dense and high-yielding varieties to address food and nutritional security. Furthermore, we describe the progress made in the fields of genomics, proteomics, metabolomics, and phenomics with an emphasis on enhancing the grain nutritional content for designing competitive biofortified varieties for the future. Considering the close genetic-relatedness within cereals, upcoming research should focus on identifying the genetic and genomic basis of nutritional traits in millets and introgressing them into major cereals through integrated omics approaches. Recent breakthroughs in the genome editing toolbox would be crucial for mainstreaming biofortification in millets.PMID:36950360 | PMC:PMC10025513 | DOI:10.3389/fpls.2023.1123655

Front Microbiol. 2023 Mar 6;14:1139386. doi: 10.3389/fmicb.2023.1139386. eCollection 2023.ABSTRACTKorean red ginseng has been widely used as an herbal medicine. Red ginseng dietary fiber (RGDF) is a residue of the processed ginseng product but still contains bioactive constituents that can be applied as prebiotics. In this study, we evaluated changes on fermentation profiles and probiotic properties of strains that belong to family Lactobacillaceae with RGDF supplementation. Metabolomic analyses were performed to understand specific mechanisms on the metabolic alteration by RGDF and to discover novel bioactive compounds secreted by the RGDF-supplemented probiotic strain. RGDF supplementation promoted short-chain fatty acid (SCFA) production, carbon source utilization, and gut epithelial adhesion of Lactiplantibacillus plantarum and inhibited attachment of enteropathogens. Intracellular and extracellular metabolome analyses revealed that RGDF induced metabolic alteration, especially associated with central carbon metabolism, and produced RGDF-specific metabolites secreted by L. plantarum, respectively. Specifically, L. plantarum showed decreases in intracellular metabolites of oleic acid, nicotinic acid, uracil, and glyceric acid, while extracellular secretion of several metabolites including oleic acid, 2-hydroxybutanoic acid, hexanol, and butyl acetate increased. RGDF supplementation had distinct effects on L. plantarum metabolism compared with fructooligosaccharide supplementation. These findings present potential applications of RGDF as prebiotics and bioactive compounds produced by RGDF-supplemented L. plantarum as novel postbiotic metabolites for human disease prevention and treatment.PMID:36950168 | PMC:PMC10025373 | DOI:10.3389/fmicb.2023.1139386

Front Microbiol. 2023 Mar 6;14:1090740. doi: 10.3389/fmicb.2023.1090740. eCollection 2023.ABSTRACTINTRODUCTION: Stringent cleaning procedures during spacecraft assembly are critical to maintaining the integrity of life-detection missions. To ensure cleanliness, NASA spacecraft are assembled in cleanroom facilities, where floors are routinely cleansed with Kleenol 30 (K30), an alkaline detergent.METHODS: Through metabolomic and cultivation approaches, we show that cultures of spacecraft-associated Acinetobacter tolerate up to 1% v/v K30 and are fully inhibited at ≥2%; in comparison, NASA cleanrooms are cleansed with ~0.8-1.6% K30.RESULTS: For A. johnsonii 2P08AA (isolated from a cleanroom floor), cultivations with 0.1% v/v K30 yield (1) no changes in cell density at late-log phase, (2) modest decreases in growth rate (~17%), (3) negligible lag phase times, (4) limited changes in the intracellular metabolome, and (5) increases in extracellular sugar acids, monosaccharides, organic acids, and fatty acids. For A. radioresistens 50v1 (isolated from a spacecraft surface), cultivations yield (1) ~50% survivals, (2) no changes in growth rate, (3) ~70% decreases in the lag phase time, (4) differential changes in intracellular amino acids, compatible solutes, nucleotide-related metabolites, dicarboxylic acids, and saturated fatty acids, and (5) substantial yet differential impacts to extracellular sugar acids, monosaccharides, and organic acids.DISCUSSION: These combined results suggest that (1) K30 manifests strain-dependent impacts on the intracellular metabolomes, cultivation kinetics, and survivals, (2) K30 influences extracellular trace element acquisition in both strains, and (3) K30 is better tolerated by the floor-associated strain. Hence, this work lends support towards the hypothesis that repeated cleansing during spacecraft assembly serve as selective pressures that promote tolerances towards the cleaning conditions.PMID:36950167 | PMC:PMC10025500 | DOI:10.3389/fmicb.2023.1090740

Pediatr Gastroenterol Hepatol Nutr. 2023 Mar;26(2):99-115. doi: 10.5223/pghn.2023.26.2.99. Epub 2023 Mar 7.ABSTRACTPURPOSE: Exclusive breastfeeding promotes gut microbial compositions associated with lower rates of metabolic and autoimmune diseases. Its cessation is implicated in increased microbiome-metabolome discordance, suggesting a vulnerability to dietary changes. Formula supplementation is common within our low-income, ethnic-minority community. We studied exclusively breastfed (EBF) neonates' early microbiome-metabolome coupling in efforts to build foundational knowledge needed to target this inequality.METHODS: Maternal surveys and stool samples from seven EBF neonates at first transitional stool (0-24 hours), discharge (30-48 hours), and at first appointment (days 3-5) were collected. Survey included demographics, feeding method, medications, medical history and tobacco and alcohol use. Stool samples were processed for 16S rRNA gene sequencing and lipid analysis by gas chromatography-mass spectrometry. Alpha and beta diversity analyses and Procrustes randomization for associations were carried out.RESULTS: Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the most abundant taxa. Variation in microbiome composition was greater between individuals than within (p=0.001). Palmitic, oleic, stearic, and linoleic acids were the most abundant lipids. Variation in lipid composition was greater between individuals than within (p=0.040). Multivariate composition of the metabolome, but not microbiome, correlated with time (p=0.030). Total lipids, saturated lipids, and unsaturated lipids concentrations increased over time (p=0.012, p=0.008, p=0.023). Alpha diversity did not correlate with time (p=0.403). Microbiome composition was not associated with each samples' metabolome (p=0.450).CONCLUSION: Neonate gut microbiomes were unique to each neonate; respective metabolome profiles demonstrated generalizable temporal developments. The overall variability suggests potential interplay between influences including maternal breastmilk composition, amount consumed and living environment.PMID:36950061 | PMC:PMC10025571 | DOI:10.5223/pghn.2023.26.2.99

Front Pharmacol. 2023 Mar 6;14:1141147. doi: 10.3389/fphar.2023.1141147. eCollection 2023.ABSTRACTAs a traditional Chinese medicine, rhubarb has been used in a variety of liver diseases and it is widely used in clinic to prevent and treat acute liver injury. Anthraquinone, as the main medicinal component of rhubarb, can reverse the further development of liver fibrosis caused by acute liver injury. In this study, metabonomics was used to explore the mechanism of different doses of rhubarb anthraquinone on acute liver injury in rats. Rhubarb anthraquinone was administered intragastric to rats at doses of 3.9, 7.8 and 15.6 mg/kg, respectively, for 7 days, and then 30% CCl4 was injected intraperitoneally at the dose of 1 ml/kg to replicate the acute liver injury model. The biochemical indicators content of ALT, AST, ALP, γ-GT, TG, TC, LDL, HDL in serum and GSH, Hyp, SOD, TNF-α, IL-6 and IL-8 in liver tissue extract were tested respectively, and liver tissue was histopathologically analysis. At the same time, UPLC-Q-TOF-MS combined with non-targeted metabolomics were used to study the metabolites and metabolic pathways of rhubarb anthraquinone in treating acute liver injury. Compared with normal rats, the contents of ALT, AST, ALP, TG, TC, LDL, γ-GT in serum and Hyp, MDA, IL-6, IL-8, TNF-α in the liver tissue extract were significantly increased in model rats (p < 0.05, p < 0.01), and the content of HDL in the serum was significantly decreased (p < 0.05); the activities of GSH and SOD in liver tissue extract were also significantly decreased (p < 0.05). After administration of rhubarb anthraquinone, compared with the model group, with the increase of dosage, some biochemical indexes showed opposite changes, and gradually approached to normal rats. 12 different metabolites were identified by metabonomics, and the biosynthesis and metabolism of phenylalanine, tyrosine and tryptophan, the metabolism of amino sugars, nucleotide sugars and pyrimidines metabolism, and the biosynthesis of steroid hormone were identified based on the biomarker analysis. Based on the biochemical analysis and metabonomics analysis of rats with acute liver injury treated with different doses of rhubarb anthraquinone, combined with histopathological observation, the results show that the protective effect of rhubarb anthraquinone on acute liver injury is related to the dosage; Meanwhile, the metabolic pathway analysis suggested that rhubarb anthraquinone alleviate acute liver injury by regulating inflammation, oxidative stress and fibrosis disorders. This study explained the therapeutic effect of rhubarb anthraquinone on acute liver injury from both material basis and action pathway, and provided safe and effective research ideas for clinical application of rhubarb.PMID:36950014 | PMC:PMC10025310 | DOI:10.3389/fphar.2023.1141147