PubMed

Aging (Albany NY). 2023 Oct 16;15. doi: 10.18632/aging.205091. Online ahead of print.ABSTRACTRecent studies indicate that inflammation is one of the causes of the development of benign prostatic hyperplasia (BPH). Inflammation may result from past infections, metabolic disorders, but also from the state of functioning of the intestinal microbiota. The aim of the study was to assess whether the diagnostic lipid parameters for metabolic syndrome and short-chain fatty acids (SCFAs) are related to the immunoexpression of interleukins in prostate tissue with benign hyperplasia. The study involved 103 men with BPH, who were divided into two groups depending on the presence of MetS. We analysed tissue immunoexpression of two proinflammatory interleukins: IL-6, which is known to be involved in the development of BPH, and IL-18, which has not been analysed so far. The results of our study indicate that men with BPH + MetS in the stroma of the prostate have a significantly higher overall percentage of IL-6+ cells compared to men without MetS (p = 0.034). The analysis of IL-18 immunoexpression in prostate tissue indicated that in men with BPH + MetS, the glandular part of the prostate had a significantly higher percentage of cells with strong IL-18 expression (p = 0.040). We also noticed a relationship between tissue expression of IL-6 and IL-18 and lipid parameters (TG and HDL). We conclude that lipid disorders occurring in men with BPH increase inflammation in the prostate gland. Moreover, it has also been demonstrated for the first time that, indirectly, through SCFAs, the gut microbiota can act to prevent or create an inflammatory microenvironment in the prostate gland.PMID:37847180 | DOI:10.18632/aging.205091

J Agric Food Chem. 2023 Oct 17. doi: 10.1021/acs.jafc.3c02669. Online ahead of print.ABSTRACTTo study the characteristics of genes and metabolites related to intramuscular fat (IMF) content with less influence by breed background and individual differences, the skeletal muscle samples from 40 Beijing black pigs with either high or low IMF content were used to perform transcriptome and metabolome analyses. About 99 genes (twofold-change) were differentially expressed. Up-regulated genes in the high IMF pigs were mainly related to fat metabolism. The key genes in charge of IMF deposition are ADIPOQ, CIDEC, CYP4B1, DGAT2, LEP, OPRL1, PLIN1, SCD, and THRSP. KLHL40, TRAFD1, and HSPA6 were novel candidate genes for the IMF trait due to their high abundances. In the low IMF pigs, the differentially expressed genes involved in virus resistance were up-regulated. About 16 and 18 differential metabolites (1.5 fold-change) were obtained in the positive and negative modes, respectively. Pigs with low IMF had weaker fatty acid oxidation due to the down-regulation of various carnitines. Differentially expressed genes were more important in determining IMF deposition than differential metabolites because relatively few differential metabolites were obtained, and they were merely the products under the physiological status of diverged IMF content. This study provided valuable information for further studies on IMF deposition.PMID:37847170 | DOI:10.1021/acs.jafc.3c02669

Plant Cell Physiol. 2023 Oct 16:pcad128. doi: 10.1093/pcp/pcad128. Online ahead of print.ABSTRACTNitrogen is one of the most essential macronutrients for plant growth and its availability in soil is vital for agricultural sustainability and productivity. However, excessive nitrogen application could reduce the nitrogen use efficiency and produce environmental pollution. Here, we systematically determined the response in lipidome and metabolome in rapeseed during nitrogen starvation. Plant growth was severely retarded during nitrogen deficiency, while the levels of most amino acids was significantly decreased. The levels of monogalactosyl diacyglycerol (MGDG) in leaves and roots was significantly decreased, while the level of digalactosyl diacylglycerol (DGDG) was significantly decreased in roots, resulting in significant reduction of MGDG/DGDG ratio during nitrogen starvation. Meanwhile, the levels of sulfoquinovosyl diacylglycerol, phosphatidylglycerol and glucuronosyl diacylglycerol was reduced to varying extents. Moreover, the levels of metabolites in the tricarboxylic acid cycle, Calvin cycle, and energy metabolism was changed during nitrogen deficiency. These findings show that nitrogen deprivation alters the membrane lipid metabolism and carbon metabolism, and our study provides valuable information to further understand the response of rapeseed to nitrogen deficiency at metabolism level.PMID:37847101 | DOI:10.1093/pcp/pcad128

Zhonghua Nan Ke Xue. 2023 Feb;29(2):165-173.ABSTRACTOBJECTIVE: To explore the regulating mechanism of the Chinese medicinal compound Qianliexin Capsules (QLX) in the treatment of chronic nonbacterial prostatitis (CNP).METHODS: We randomly divided 18 SPF SD male rats into a normal control (n = 6), a model control (n = 6) and a QLX group (n = 6). After successful establishment of a CNP model in the latter two groups by injecting 50 μl 1% carrageenan bilaterally into the prostate, we treated the rats in the QLX group by intragastrical administration of QLX at 4 g/kg, tid, and those in the normal and model control groups with the same volume of pure water, all for 45 days. Then, we examined the possible lower urinary tract symptoms (LUTS) of CNP by detecting the prostate indexes, expression of the tissue inflammatory factor IL-1 β, 24-hour urine volume and pain threshold reaction (PTR) time, and conducted a metabonomics analysis of the urine and plasma samples.RESULTS: Compared with the normal controls, the CNP model rats showed dramatically increased prostate coefficient (［0.75 ± 0.09］ ‰ vs ［1.60 ± 0.35］ ‰, P < 0.01) and the expression of IL-1β (［22.61 ± 2.77］ vs ［55.12 ± 4.94］ ng/ml, P < 0.01), which were both decreased in the QLX group (［0.97 ± 0.10］ ‰ and ［36.64 ± 7.25］ ng/ml) in comparison with those in the model controls (P < 0.01). The urine volume was remarkably reduced in the model control group compared with that in the normal controls (4 ml vs 16.38 ml, P < 0.01), and so was the PTR time (［13.83 ± 5.67］ vs ［23.73 ± 2.52］ s, P < 0.01), while the levels of urea nitrogen (［23.06 ± 3.71］ vs ［17.92 ± 1.41］ mg/dL, P < 0.01), creatinine (［48.08 ± 9.31］ vs ［40.31 ± 3.53］ μmol/L, P < 0.01) and uric acid (［181.36 ± 64.06］ vs ［84.33 ± 21.40］ μmol/L, P < 0.01) increased significantly. The animals in the QLX group exhibited significant improvement in the urine volume (［13.44 ± 2.26］ ml), PTR time (［31.45 ± 2.96］ s), urea nitrogen (［16.49 ± 1.86］ mg/dL), creatinine (［36.88 ± 7.98］ μmol/L) and uric acid (［117.47 ± 40.09］ μmol/L) in comparison with the model controls (P < 0.01). Metabonomics analysis revealed a reversing effect of QLX on the carrageenin-induced alteration in a variety of metabolites in the urine and serum, restoring the ratios of such metabolites as glycine, cysteine, ketoimine quinolinic acid, aminobutyraldehyde and triphosphate to almost normal. Pathway enrichment analysis showed that the main metabolic pathways were aspartate and glutamate pathways. The ratios of such metabolites as neuroside, adipic acid, diacylglycerol, choline lecithin and so on in the plasma sample were dramatically improved in the QLX group compared with those in the model controls (P < 0.01).CONCLUSION: QLX significantly improves the symptoms of CNP and has a definite effect on amino acids, phosphatidyl and other biomarkers through the tricarboxylic acid cycle, amino acid metabolism, lipid metabolism and other related pathways.PMID:37847089

mBio. 2023 Oct 17:e0153123. doi: 10.1128/mbio.01531-23. Online ahead of print.ABSTRACTHelicobacter pylori (H. pylori) has been regarded as a definite carcinogenic bacterium for gastric cancer (GC). This multi-omics research was designed to investigate the genetic, microbial, and metabolic changes of GC patients when they are infected with H. pylori. We first mined The Cancer Genome Atlas Stomach Adenocarcinoma (STAD) data to identify the key genes and critical pathways in H. pylori-positive individuals with GC compared to H. pylori-negative individuals with GC. Then, fresh stool samples were collected from GC individuals screened for eligibility, and we analyzed the microbial changes and metabolite alterations between H. pylori-positive and H. pylori-negative GC individuals. Finally, we tried to explore the interaction between key gut flora and metabolite changes in GC patients infected with H. pylori. We identified three genes (GCG, APOA1, and IGFBP1) with significant relevance to H. pylori infection, and the survival monogram based on the three H. pylori-related genes showed good predictive ability for overall survival among GC individuals. 16S rRNA sequencing showed that the abundance of Escherichia-Shigella, Bacteroides, Enterococcus, and Lactobacillus was upregulated in GC cases with H. pylori at the level of genus. There exists a great difference in alpha and beta diversity between H. pylori group and non-H. pylori group. The untargeted metabolome analysis identified 295 significant fecal metabolites, and the levels of penitrem E, auberganol, stercobilinogen, and lys thr are upregulated in the H. pylori group. Finally, correlation analysis showed that there exists a significant correlation between the fecal metabolites and gut bacterial strains. This is the first clinical research to investigate the difference between GC patients with H. pylori and GC patients without H. pylori via multi-omics analysis. 16S rRNA sequencing along with untargeted metabolomics demonstrated decreased microbial diversity and metabolic dysregulation in gastric carcinoma individuals with H. pylori infection.IMPORTANCEThis is the first clinical research to systematically expound the difference between gastric cancer (GC) individuals with Helicobacter pylori and GC individuals without H. pylori from the perspective of multi-omics. This clinical study identified significant genes, microbes, and fecal metabolites, which exhibited nice power for differentiating GC individuals with H. pylori infection from GC individuals without H. pylori infection. This study provides a crucial basis for a better understanding of eradication therapy among the GC population.PMID:37846989 | DOI:10.1128/mbio.01531-23

Mol Plant Pathol. 2023 Oct 17. doi: 10.1111/mpp.13395. Online ahead of print.ABSTRACTPlant-pathogenic Ralstonia strains cause bacterial wilt disease by colonizing xylem vessels of many crops, including tomato. Host resistance is the best control for bacterial wilt, but resistance mechanisms of the widely used Hawaii 7996 tomato breeding line (H7996) are unknown. Using growth in ex vivo xylem sap as a proxy for host xylem, we found that Ralstonia strain GMI1000 grows in sap from both healthy plants and Ralstonia-infected susceptible plants. However, sap from Ralstonia-infected H7996 plants inhibited Ralstonia growth, suggesting that in response to Ralstonia infection, resistant plants increase inhibitors in their xylem sap. Consistent with this, reciprocal grafting and defence gene expression experiments indicated that H7996 wilt resistance acts in both above- and belowground plant parts. Concerningly, H7996 resistance is broken by Ralstonia strain UW551 of the pandemic lineage that threatens highland tropical agriculture. Unlike other Ralstonia, UW551 grew well in sap from Ralstonia-infected H7996 plants. Moreover, other Ralstonia strains could grow in sap from H7996 plants previously infected by UW551. Thus, UW551 overcomes H7996 resistance in part by detoxifying inhibitors in xylem sap. Testing a panel of xylem sap compounds identified by metabolomics revealed that no single chemical differentially inhibits Ralstonia strains that cannot infect H7996. However, sap from Ralstonia-infected H7996 contained more phenolic compounds, which are known to be involved in plant antimicrobial defence. Culturing UW551 in this sap reduced total phenolic levels, indicating that the resistance-breaking Ralstonia strain degrades these chemical defences. Together, these results suggest that H7996 tomato wilt resistance depends in part on inducible phenolic compounds in xylem sap.PMID:37846613 | DOI:10.1111/mpp.13395

J Diabetes. 2023 Oct 17. doi: 10.1111/1753-0407.13485. Online ahead of print.ABSTRACTBACKGROUND: Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes.METHODS: Fourteen eligible patients received three allogenic WMTs and were followed up at 1 week, 1 month, and 3 months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self-monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms.RESULTS: Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1 month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia-Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C-peptide.CONCLUSIONS: WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes.PMID:37846600 | DOI:10.1111/1753-0407.13485

Biomark Insights. 2023 Oct 14;18:11772719231204508. doi: 10.1177/11772719231204508. eCollection 2023.ABSTRACTCancer is a complex and heterogeneous disease that poses a significant threat to global health. Early diagnosis and treatment are critical for improving patient outcomes, and the use of liquid biopsies has emerged as a promising approach for cancer detection and monitoring. Traditionally, cancer diagnosis has relied on invasive tissue biopsies, the collection of which can prove challenging for patients and the results of which may not always provide accurate results due to tumor heterogeneity. Liquid biopsies have gained increasing attention as they provide a non-invasive and accessible source of cancer biomarkers, which can be used to diagnose cancer, monitor treatment response, and detect relapse. The integration of -omics technologies, such as proteomics, genomics, and metabolomics, has further enhanced the capabilities of liquid biopsies by introducing precision oncology and enabling the tailoring of treatment for individual patients based on their unique tumor biology. In this review, we will discuss the challenges and advances in the field of cancer liquid biopsies and the integration of -omics technologies for different types of liquid biopsies, including blood, tear, urine, sweat, saliva, and cerebrospinal fluid.PMID:37846373 | PMC:PMC10576933 | DOI:10.1177/11772719231204508

Clin Transl Med. 2023 Oct;13(10):e1236. doi: 10.1002/ctm2.1236.ABSTRACTOBJECTIVE: To reveal whether gut microbiota and their metabolites are correlated with oocyte quality decline caused by circadian rhythm disruption, and to search possible approaches for improving oocyte quality.DESIGN: A mouse model exposed to continuous light was established. The oocyte quality, embryonic development, microbial metabolites and gut microbiota were analyzed. Intragastric administration of microbial metabolites was conducted to confirm the relationship between gut microbiota and oocyte quality and embryonic development.RESULTS: Firstly, we found that oocyte quality and embryonic development decreased in mice exposed to continuous light. Through metabolomics profiling and 16S rDNA-seq, we found that the intestinal absorption capacity of vitamin D was decreased due to significant decrease of bile acids such as lithocholic acid (LCA), which was significantly associated with increased abundance of Turicibacter. Subsequently, the concentrations of anti-Mullerian hormone (AMH) hormone in blood and melatonin in follicular fluid were reduced, which is the main reason for the decline of oocyte quality and early embryonic development, and this was rescued by injection of vitamin D3 (VD3). Secondly, melatonin rescued oocyte quality and embryonic development by increasing the concentration of lithocholic acid and reducing the concentration of oxidative stress metabolites in the intestine. Thirdly, we found six metabolites that could rescue oocyte quality and early embryonic development, among which LCA of 30 mg/kg and NorDCA of 15 mg/kg had the best rescue effect.CONCLUSION: These findings confirm the link between ovarian function and gut microbiota regulation by microbial metabolites and have potential value for improving ovary function.PMID:37846137 | DOI:10.1002/ctm2.1236

BMC Pediatr. 2023 Oct 16;23(1):508. doi: 10.1186/s12887-023-04346-x.ABSTRACTBACKGROUND: Oropharyngeal administration of colostrum (OAC) has an immune-stimulating effect on oropharyngeal-associated lymphoid tissue, and can promote the maturation of the gastrointestinal tract. However, how OAC promotes intestinal maturation in preterm infants by altering gut microbiota remains unclear. We aim to assess changes in gut microbiota and metabolites after OAC in very preterm infants.METHODS: A multicenter, double-blind, randomized controlled trial will be conducted in three large neonatal intensive care units in Shenzhen, China, with preterm infants with gestational age less than 32 weeks at birth and birth weight less than 1500 g. It is estimated that 320 preterm infants will be enrolled in this study within one year. The intervention group will receive oropharyngeal administration of 0.2 ml colostrum every 3 h, starting between the first 48 to 72 h and continued for 5 consecutive days. Following a similar administration scheme, the control group will receive oropharyngeal administration of sterile water. Stool samples will be collected at the first defecation, as well as on the 7th, 14th, 21st and 28th days after birth for analysis of effect of OAC on gut microbiota and metabolites through 16sRNA gene sequencing and liquid chromatography-mass spectrometry.DISCUSSION: This proposal advocates for the promotion of OAC as a safe and relatively beneficial protocol in neonatal intensive care units, which may contribute to the establishment of a dominant intestinal flora. Findings of this study may help improve the health outcomes of preterm infants by establishment of targeted gut microbiota in future studies.TRIAL REGISTRATION: NCT05481866 (registered July 30, 2022 on ClinicalTrials.gov).PMID:37845612 | DOI:10.1186/s12887-023-04346-x

BMC Neurosci. 2023 Oct 16;24(1):54. doi: 10.1186/s12868-023-00824-1.ABSTRACTBACKGROUND: Diagnosis and prognostication of severe traumatic brain injury (sTBI) continue to be problematic despite years of research efforts. There are currently no clinically reliable biomarkers, though advances in protein biomarkers are being made. Utilizing Omics technology, particularly metabolomics, may provide new diagnostic biomarkers for sTBI. Several published studies have attempted to determine the specific metabolites and metabolic pathways involved; these studies will be reviewed.AIMS: This scoping review aims to summarize the current literature concerning metabolomics in sTBI, review the comprehensive data, and identify commonalities, if any, to define metabolites with potential clinical use. In addition, we will examine related metabolic pathways through pathway analysis.METHODS: Scoping review methodology was used to examine the current literature published in Embase, Scopus, PubMed, and Medline. An initial 1090 publications were identified and vetted with specific inclusion criteria. Of these, 20 publications were selected for further examination and summary. Metabolic data was classified using the Human Metabolome Database (HMDB) and arranged to determine the 'recurrent' metabolites and classes found in sTBI. To help understand potential mechanisms of injury, pathway analysis was performed using these metabolites and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database.RESULTS: Several metabolites related to sTBI and their effects on biological pathways were identified in this review. Across the literature, proline, citrulline, lactate, alanine, valine, leucine, and serine all decreased in adults post sTBI, whereas both octanoic and decanoic acid increased. Hydroxy acids and organooxygen compounds generally increased following sTBI, while most carboxylic acids decreased. Pathway analysis showed significantly affected glycine and serine metabolism, glycolysis, branched-chain amino acid (BCAA) metabolism, and other amino acid metabolisms. Interestingly, no tricarboxylic acid cycle metabolites were affected.CONCLUSION: Aside from a select few metabolites, classification of a metabolic profile proved difficult due to significant ambiguity between study design, sample size, type of sample, metabolomic detection techniques, and other confounding variables found in sTBI literature. Given the trends found in some studies, further metabolomics investigation of sTBI may be useful to identify clinically relevant metabolites.PMID:37845610 | DOI:10.1186/s12868-023-00824-1

Pediatr Res. 2023 Oct 16. doi: 10.1038/s41390-023-02862-1. Online ahead of print.NO ABSTRACTPMID:37845524 | DOI:10.1038/s41390-023-02862-1

Nat Aging. 2023 Oct 16. doi: 10.1038/s43587-023-00498-8. Online ahead of print.ABSTRACTAdvanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that the spermidine level was reduced in ovaries of aged mice and that supplementation with spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By microtranscriptomic analysis, we further discovered that spermidine-induced recovery of oocyte quality was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this mechanism of action was conserved in porcine oocytes under oxidative stress. Altogether, our findings suggest that spermidine supplementation could represent a therapeutic strategy to ameliorate oocyte quality and reproductive outcome in cis-gender women and other persons trying to conceive at an advanced age. Future work is needed to test whether this approach can be safely and effectively translated to humans.PMID:37845508 | DOI:10.1038/s43587-023-00498-8

Commun Med (Lond). 2023 Oct 16;3(1):145. doi: 10.1038/s43856-023-00365-y.ABSTRACTBACKGROUND: Diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, confounders such as sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider sex, as well as arterial hypertension (AHT), when investigating COVID-19-positive serum samples in a large age-and sex matched cohort.METHODS: NMR serum data from 329 COVID-19 patients were compared with 305 healthy controls. 134 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Sex was considered in detail for all comparisons.RESULTS: Here, we show that several differences emerge from previous NMR COVID-19 studies when AHT is considered. Especially, the previously described triglyceride-rich lipoprotein profile is no longer observed in COVID-19 patients, nor an increase in ketone bodies. Further alterations are a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Additionally, hypertensive COVID-19 patients show higher inflammatory NMR parameters than normotensive patients.CONCLUSIONS: We present a more precise picture of COVID-19 blood serum parameters. Accordingly, considering sex and comorbidities should be included in future metabolomics studies for improved and refined patient stratification. Due to metabolic similarities with other viral infections, these results can be applied to other respiratory diseases in the future.PMID:37845506 | DOI:10.1038/s43856-023-00365-y

Cell Death Differ. 2023 Oct 16. doi: 10.1038/s41418-023-01232-y. Online ahead of print.ABSTRACTBCL2 is an apoptosis-inhibitory oncoprotein that also possesses apoptosis-unrelated activities. Pharmacological BCL2 inhibitors have been developed with the scope of driving BCL2-dependent cancer cells into apoptosis, and one BCL2 antagonist, venetoclax, has been clinically approved for the treatment of specific leukemias and lymphomas. Nonetheless, it appears that venetoclax, as well as genetic BCL2 inhibition, can mediate anticancer effects through an indirect action. Such an indirect effect relies on the enhancement of the immunostimulatory function of dendritic cells, hence increasing tumor immunosurveillance. Mechanistically, BCL2 inhibition involves improved antigen presentation by conventional type-1 dendritic cells (cDC1s) due to the activation of an interferon response, leading to a T cell-mediated anticancer immune response that can be further enhanced by PD-1 blockade. These findings support the emerging hypothesis that successful antineoplastic drugs generally mediate their effects indirectly, through the immune system, rather via merely cell-autonomous effects on malignant cells.PMID:37845384 | DOI:10.1038/s41418-023-01232-y

Sci Rep. 2023 Oct 16;13(1):17591. doi: 10.1038/s41598-023-44690-7.ABSTRACTUrine is ideal for non-targeted metabolomics, providing valuable insights into normal and pathological cellular processes. Optimal extraction is critical since non-targeted metabolomics aims to analyse various compound classes. Here, we optimised a low-volume urine preparation procedure for non-targeted GC-MS. Five extraction methods (four organic acid [OA] extraction variations and a "direct analysis" [DA] approach) were assessed based on repeatability, metabolome coverage, and metabolite recovery. The DA method exhibited superior repeatability, and achieved the highest metabolome coverage, detecting 91 unique metabolites from multiple compound classes comparatively. Conversely, OA methods may not be suitable for all non-targeted metabolomics applications due to their bias toward a specific compound class. In accordance, the OA methods demonstrated limitations, with lower compound recovery and a higher percentage of undetected compounds. The DA method was further improved by incorporating an additional drying step between two-step derivatization but did not benefit from urease sample pre-treatment. Overall, this study establishes an improved low-volume urine preparation approach for future non-targeted urine metabolomics applications using GC-MS. Our findings contribute to advancing the field of metabolomics and enable efficient, comprehensive analysis of urinary metabolites, which could facilitate more accurate disease diagnosis or biomarker discovery.PMID:37845360 | DOI:10.1038/s41598-023-44690-7

Nat Microbiol. 2023 Oct 16. doi: 10.1038/s41564-023-01493-w. Online ahead of print.ABSTRACTProgression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.PMID:37845315 | DOI:10.1038/s41564-023-01493-w

Sci Rep. 2023 Oct 16;13(1):17516. doi: 10.1038/s41598-023-44629-y.ABSTRACTChronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP-UPLC-MS/MS) and hydrophilic interaction liquid chromatography (HILIC)-UPLC-MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic acid, thyroxine, and 3-beta-Hydroxy-5-cholestenoate were found to be significantly downregulated. 3-beta-Hydroxy-5-cholestenoate was downregulated more significantly in male than female kidneys. Trichome Staining also showed remarkable kidney fibrosis in mice subjected to chronic hypoxia. Our study offers potential intracellular metabolite signatures for hypoxic kidneys.PMID:37845304 | DOI:10.1038/s41598-023-44629-y

Sci Rep. 2023 Oct 16;13(1):17596. doi: 10.1038/s41598-023-44741-z.ABSTRACTThe study aimed to assess the impact of dehydrated citrus pulp (DCP) on growth performance, fecal characteristics, fecal bacterial composition (based on 16S rRNA analysis), and fecal and serum metabolomic profiles in crossbred pigs. 80 finishing pigs Duroc × (Landrace × Large White) were fed either a control diet (C) or a diet with 240 g/kg DCP (T) for six weeks. Including DCP in diets tended to decrease feed intake, increased (p < 0.05) the concentrations of acetic and heptanoic acids and decreased (p < 0.05) fecal butyric and branched-chain fatty acid concentrations in feces. Animals fed DCP exhibited a lower abundance of the genera Clostridium and Romboutsia, while Lachnospira significantly increased. Orthogonal partial least squares discriminant analysis plotted a clear separation of fecal and serum metabolites between groups. The main discriminant fecal metabolites were associated with bacterial protein fermentation and were downregulated in T-fed pigs. In serum, DCP supplementation upregulated metabolites related to protein and fatty acids metabolism. In conclusion, the addition of DCP as an environmentally friendly source of nutrients in pig diets, resulted in modifications of fecal bacterial composition, fermentation patterns, and overall pig metabolism, suggesting improvements in protein metabolism and gut health.PMID:37845279 | DOI:10.1038/s41598-023-44741-z

Trends Endocrinol Metab. 2023 Oct 14:S1043-2760(23)00195-9. doi: 10.1016/j.tem.2023.09.006. Online ahead of print.ABSTRACTThe identification of novel secreted factors is advancing at an unprecedented pace. However, there is a critical need to consolidate and integrate this knowledge to provide a framework of their diverse mechanisms, functional significance, and inter-relationships. Complicating this effort are challenges related to nonstandardized methods, discrepancies in sample handling, and inconsistencies in the annotation of unknown molecules. This Review aims to synthesize the rapidly expanding field of the metabolic secretome, encompassing the five major types of secreted factors: proteins, peptides, metabolites, lipids, and extracellular vesicles. By systematically defining the functions and detection of the components within the metabolic secretome, this Review provides a primer into the advances of the field, and how integration of the techniques discussed can provide a deeper understanding of the mechanisms underlying metabolic homeostasis and its disorders.PMID:37845120 | DOI:10.1016/j.tem.2023.09.006