PubMed

Bioinformatics. 2023 Oct 9:btad618. doi: 10.1093/bioinformatics/btad618. Online ahead of print.ABSTRACTMOTIVATION: Multiple factors can impact accuracy and reproducibility of mass spectrometry data. There is a need to integrate quality assessment and control into data analytic workflows.RESULTS: The MsQuality package calculates 43 low-level quality metrics based on the controlled mzQC vocabulary defined by the HUPO-PSI on a single mass spectrometry-based measurement of a sample. It helps to identify low-quality measurements and track data quality. Its use of community-standard quality metrics facilitates comparability of quality assessment and control (QA/QC) criteria across datasets.AVAILABILITY: The R package MsQuality is available through Bioconductor at https://bioconductor.org/packages/MsQuality.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:37812234 | DOI:10.1093/bioinformatics/btad618

Microbiol Spectr. 2023 Oct 9:e0178623. doi: 10.1128/spectrum.01786-23. Online ahead of print.ABSTRACTMicrobial community imbalance is the main cause of soybean intercropping, but the mechanism of soybean soil fungal community diversity change induced by continuous cropping is still unclear. This study analyzes the fungal community diversity and the change of fungal communities in compartments of different root systems of intercropped soybeans by high-throughput sequencing (endosphere, rhizoplane, and rhizosphere) between continuous cropping and maize-soybean rotation. The results showed that the community composition and the diversity of compartments of different root systems of intercropped soybeans are different, and fungal diversities showed a decreasing trend from rhizosphere to endosphere. Continuous cropping significantly increased fungal community diversities in different root compartments and changed their formation, enrichment, and depletion processes. Continuous cropping brings about the enrichment of soil pathogens, but only partial soil pathogens could colonize from the rhizosphere to the endosphere. All these suggested that root compartments had selective effects on root-associated fungal community diversity. Additionally, metabolomics assay revealed that continuous cropping soybean markedly altered soil metabolic profiling. Correlation analysis results showed that fungal community diversity was significantly correlated with soil metabolites. To sum up, under different planting patterns, the diversity and the functional mode of soybean soil microbial community have changed. Continuous cropping has increased the abundance of pathogenic fungi in soybean soil, resulting in changes in the correlation between soil fungi and metabolites, and then changed the soil metabolic spectrum.IMPORTANCESoybean yield can be affected by soybean soil fungal communities in different tillage patterns. Soybean is an important food crop with great significance worldwide. Continuous cultivation resulted in soil nutrient deficiencies, disordered metabolism of root exudates, fungal pathogen accumulation, and an altered microbial community, which brought a drop in soybean output. In this study, taking the soybean agroecosystem in northeast China, we revealed the microbial ecology and soil metabolites spectrum, especially the diversity and composition of soil fungi and the correlation of pathogenic fungi, and discussed the mechanisms and the measures of alleviating the obstacles.PMID:37811990 | DOI:10.1128/spectrum.01786-23

J Leukoc Biol. 2023 Oct 9:qiad121. doi: 10.1093/jleuko/qiad121. Online ahead of print.ABSTRACTMacrophages are key immune cells that can adapt their metabolic phenotype in response to different stimuli. Lysine deacetylases (KDAC) are important enzymes regulating inflammatory gene expression and KDAC inhibitors have been shown to exert anti-inflammatory effects in models of chronic obstructive pulmonary disease (COPD). We hypothesized that these anti-inflammatory effects may be associated with metabolic changes in macrophages. To validate this hypothesis, we used an unbiased and a targeted proteomic approach to investigate metabolic enzymes as well as LC- and GC-MS to quantify metabolites in combination with the measurement of functional parameters in primary murine alveolar-like macrophages after lipopolysaccharide (LPS)-induced activation in the presence or absence of KDAC inhibition. We found that KDAC inhibition resulted in reduced production of inflammatory mediators such as TNF-α and IL-1β. However, only minor changes in macrophage metabolism were observed, as only one of the KDAC inhibitors slightly increased mitochondrial respiration while no changes in metabolite levels were seen. However, KDAC inhibition specifically enhanced expression of proteins involved in ubiquitination, which may be a driver of the anti-inflammatory effects of KDAC inhibitors. Our data illustrate that a multi-omics approach provides novel insights into how macrophages interact with cues from their environment. More detailed studies investigating ubiquitination as a potential driver of KDAC inhibition will help developing novel anti-inflammatory drugs for difficult to treat diseases such as COPD.PMID:37811856 | DOI:10.1093/jleuko/qiad121

Physiol Genomics. 2023 Oct 9. doi: 10.1152/physiolgenomics.00072.2023. Online ahead of print.ABSTRACTCardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in chronic stable angina (CSA) and acute coronary syndrome (ACS) patients compared to healthy controls. Bacterial alpha diversity in stool from ACS or CSA patients was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units assigned to commensal taxa differentiating ACS patients from healthy controls at both baseline and follow up. Both CSA and ACS patients had significantly higher levels of trimethylamine N-oxide compared to healthy controls (CSA; 0.032 ± 0.023 mmol/L, p <0.01 vs healthy and ACS; 0.032 ± 0.023 mmol/L, p =0.02 vs healthy respectively). ACS patients had reduced levels of propionate, and butyrate (119 ± 4 vs 139 ± 5.1 µM, p =0.001 and 14 ± 4.3 vs 23.5 ± 8.1 µM, p <0.001 respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs 1834 ± 45.8 ng/mL, p <0.0001) and sCD163 levels (457.3 ± 31.8 vs 326.8 ± 20.7 ng/mL, p =0.001), compared to healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in both CSA and ACS patients compared to healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD.PMID:37811721 | DOI:10.1152/physiolgenomics.00072.2023

Am J Physiol Regul Integr Comp Physiol. 2023 Oct 9. doi: 10.1152/ajpregu.00246.2022. Online ahead of print.ABSTRACTDuchenne muscular dystrophy (DMD), a progressive muscle disease caused by the absence of functional dystrophin protein, is associated with multiple cellular, physiological, and metabolic dysfunctions. As an added complication to the primary insult, obesity/insulin resistance (O/IR) is frequently reported in DMD patients; however, how IR impacts disease severity is unknown. We hypothesized a high-fat, high sucrose diet (HFHSD) would induce O/IR, exacerbate disease severity, and cause metabolic alterations in dystrophic mice. To test this hypothesis, we treated 7-wk old mdx (disease model) and C57 mice with a control diet (CD) or a HFHSD for 15 weeks. The HFHSD induced insulin resistance, glucose intolerance and hyperglycemia in C57 and mdx mice. Of note, mdx mice on CD were also insulin resistant. Additionally, visceral adipose tissue weights were increased with HFHSD in C57 and mdx mice though differed by genotype. Serum creatine kinase activity and histopathological analyses using Masson's trichrome staining in diaphragm indicated muscle damage was driven by dystrophin deficiency but was not augmented by diet. In addition, markers of inflammatory signaling, mitochondrial abundance, and autophagy were impacted by disease but not diet. Despite this, in addition to disease signatures in CD-fed mice, metabolomic and lipidomic analyses demonstrated a HFHSD caused some common changes in C57 and mdx mice and some unique signatures of O/IR within the context of dystrophin deficiency. In total, these data revealed that in mdx mice, 15 weeks of a HFHSD did not overtly exacerbate muscle injury but further impaired the metabolic status of dystrophic muscle.PMID:37811713 | DOI:10.1152/ajpregu.00246.2022

Front Nutr. 2023 Sep 22;10:1243503. doi: 10.3389/fnut.2023.1243503. eCollection 2023.ABSTRACTThe study of fermentation and brewing has a long history of pioneering discoveries that continue to influence modern industrial food production. Since then, numerous research endeavors have yielded conventional criteria that guide contemporary brewing practices. However, the intricate open challenges faced today necessitate a more exhaustive understanding of the process at the molecular scale. We have developed an ultra-high-resolution mass spectrometric analysis (FT-ICR-MS) of the brewing process that can rapidly and comprehensively resolve thousands of molecules. This approach allows us to track molecular fluctuation during brewing at the level of chemical compositions. Employing biological triplicates, our investigation of two brewing lines that are otherwise identical except for the malt used revealed over 8,000 molecular descriptors of the brewing process. Metabolite imprints of both the similarities and differences arising from deviating malting temperatures were visualized. Additionally, we translated traditional brewing attributes such as the EBC-value, free amino nitrogen, pH-value, and concentration curves of specific molecules, into highly correlative molecular patterns consisting of hundreds of metabolites. These in-depth molecular imprints provide a better understanding of the molecular circumstances leading to various changes throughout the brewing process. Such chemical maps go beyond the observation of traditional brewing attributes and are of great significance in the investigation strategies of current open challenges in brewing research. The molecular base of knowledge, along with advancements in technological and data integration schemes, can facilitate the efficient monitoring of brewing and other productions processes.PMID:37810931 | PMC:PMC10557258 | DOI:10.3389/fnut.2023.1243503

ACS Omega. 2023 Sep 20;8(39):35555-35570. doi: 10.1021/acsomega.3c00122. eCollection 2023 Oct 3.ABSTRACTFu-Zheng-Qu-Xie (FZQX) decoction is a traditional Chinese herbal prescription for the treatment of lung cancer and exerts proapoptotic and immunomodulatory effects. It has been clinically suggested to be effective in improving the survival of postoperative early-stage lung adenocarcinoma (LUAD), but the mechanism remains unclear. In this study, we used network pharmacology coupled with metabolomics approaches to explore the pharmacological action and effective mechanism of FZQX against the recurrence and metastasis of postoperative early-stage LUAD. Network pharmacology analysis showed that FZQX could prevent the recurrence and metastasis of postoperative early-stage LUAD by regulating a series of targets involving vascular endothelial growth factor receptor 2, estrogen receptor 1, sarcoma gene, epidermal growth factor receptor, and protein kinase B and by influencing the Ras, PI3K-Akt, and mitogen-activated protein kinase signaling pathways. In liquid chromatography-mass spectrometry analysis, 11 differentially expressed metabolites, including PA(12:0/18:4(6Z,9Z,12Z,15Z)), PC(16:0/0:0)[U], LysoPC(18:1(11Z)), and LysoPC(18:0), were discovered in the FZQX-treated group compared to those in the model group before treatment or normal group. They were enriched in cancer metabolism-related signaling pathways such as central carbon metabolism in cancer, choline metabolism, and glycerol phospholipid metabolism. Collectively, our results suggest that the multicomponent and multitarget interaction network of FZQX inhibits the recurrence and metastasis of postoperative early-stage LUAD by activating the receptor signal transduction pathway to inhibit proliferation, induce cell apoptosis, inhibit aerobic glycolysis, and reprogram tumor lipid metabolism.PMID:37810735 | PMC:PMC10552138 | DOI:10.1021/acsomega.3c00122

Front Plant Sci. 2023 Sep 22;14:1111875. doi: 10.3389/fpls.2023.1111875. eCollection 2023.ABSTRACTDrought (D) and heat (H) are the two major abiotic stresses hindering cereal crop growth and productivity, either singly or in combination (D/+H), by imposing various negative impacts on plant physiological and biochemical processes. Consequently, this decreases overall cereal crop production and impacts global food availability and human nutrition. To achieve global food and nutrition security vis-a-vis global climate change, deployment of new strategies for enhancing crop D/+H stress tolerance and higher nutritive value in cereals is imperative. This depends on first gaining a mechanistic understanding of the mechanisms underlying D/+H stress response. Meanwhile, functional genomics has revealed several stress-related genes that have been successfully used in target-gene approach to generate stress-tolerant cultivars and sustain crop productivity over the past decades. However, the fast-changing climate, coupled with the complexity and multigenic nature of D/+H tolerance suggest that single-gene/trait targeting may not suffice in improving such traits. Hence, in this review-cum-perspective, we advance that targeted multiple-gene or metabolic pathway manipulation could represent the most effective approach for improving D/+H stress tolerance. First, we highlight the impact of D/+H stress on cereal crops, and the elaborate plant physiological and molecular responses. We then discuss how key primary metabolism- and secondary metabolism-related metabolic pathways, including carbon metabolism, starch metabolism, phenylpropanoid biosynthesis, γ-aminobutyric acid (GABA) biosynthesis, and phytohormone biosynthesis and signaling can be modified using modern molecular biotechnology approaches such as CRISPR-Cas9 system and synthetic biology (Synbio) to enhance D/+H tolerance in cereal crops. Understandably, several bottlenecks hinder metabolic pathway modification, including those related to feedback regulation, gene functional annotation, complex crosstalk between pathways, and metabolomics data and spatiotemporal gene expressions analyses. Nonetheless, recent advances in molecular biotechnology, genome-editing, single-cell metabolomics, and data annotation and analysis approaches, when integrated, offer unprecedented opportunities for pathway engineering for enhancing crop D/+H stress tolerance and improved yield. Especially, Synbio-based strategies will accelerate the development of climate resilient and nutrient-dense cereals, critical for achieving global food security and combating malnutrition.PMID:37810398 | PMC:PMC10557149 | DOI:10.3389/fpls.2023.1111875

Front Plant Sci. 2023 Sep 21;14:1282465. doi: 10.3389/fpls.2023.1282465. eCollection 2023.NO ABSTRACTPMID:37810395 | PMC:PMC10552640 | DOI:10.3389/fpls.2023.1282465

Front Plant Sci. 2023 Sep 22;14:1292878. doi: 10.3389/fpls.2023.1292878. eCollection 2023.NO ABSTRACTPMID:37810378 | PMC:PMC10556855 | DOI:10.3389/fpls.2023.1292878

iScience. 2023 Sep 19;26(10):107948. doi: 10.1016/j.isci.2023.107948. eCollection 2023 Oct 20.ABSTRACTThe metabolic alterations caused by SARS-CoV-2 infection reflect disease progression. To analyze molecules involved in these metabolic changes, a multiomics study was performed using plasma from 103 patients with different degrees of COVID-19 severity during the evolution of the infection. With the increased severity of COVID-19, changes in circulating proteomic, metabolomic, and lipidomic profiles increased. Notably, the group of severe and critical patients with high HRG and ChoE (20:3) and low alpha-ketoglutaric acid levels had a high chance of unfavorable disease evolution (AUC = 0.925). Consequently, patients with the worst prognosis presented alterations in the TCA cycle (mitochondrial dysfunction), lipid metabolism, amino acid biosynthesis, and coagulation. Our findings increase knowledge regarding how SARS-CoV-2 infection affects different metabolic pathways and help in understanding the future consequences of COVID-19 to identify potential therapeutic targets.PMID:37810253 | PMC:PMC10551651 | DOI:10.1016/j.isci.2023.107948

Heliyon. 2023 Sep 14;9(9):e19949. doi: 10.1016/j.heliyon.2023.e19949. eCollection 2023 Sep.ABSTRACTQijiao Shengbai capsule (QJSB) is formulated according to the traditional Chinese medicine formula, its function is to nourish Qi and blood, improve the body's immunity. Leukopenia has been treated with it in clinical settings. However, the mechanism of leukopenia from the perspective of intestinal tract has not been reported. This study combined metabolomics and 16S rRNA sequencing technologies to investigate the mechanism of QJSB on leukopenia from the intestine. As a result of cyclophosphamide induction in mice, the results demonstrated that QJSB may greatly increase the quantity of peripheral leukocytes (including neutrophils). Meanwhile, QJSB had a restorative effect on the colon of leukopenic mice; it also increased the level of IL-2, IL-6 and G-CSF in the intestine, further enhancing the immunity and hematopoietic function of mice. Metabolic studies showed that QJSB altered 27 metabolites, most notably amino acid metabolism. In addition, QJSB had a positive regulatory effect on the intestinal microbiota, and could alter community composition by improving the diversity and abundance of the intestinal microbial, which mainly involved 6 related bacterial groups, and primarily regulates three associated SCFAs (acetic acid, butyrate acid and valeric acid). Therefore, this study suggests that QJSB can improve hematopoietic function, enhance the immune system, relieve leucopenia and improve the gut in leucopenic mice by modulating metabolic response pathways, fecal metabolites and intestinal microbiota.PMID:37810141 | PMC:PMC10559567 | DOI:10.1016/j.heliyon.2023.e19949

Heliyon. 2023 Sep 9;9(9):e20034. doi: 10.1016/j.heliyon.2023.e20034. eCollection 2023 Sep.ABSTRACTPodocarpus is the most dominant genus of Podocarpaceae, with higher taxonomical proximity to the Taxaceae, having numerous pharmaceutical applications, however, scarce studies dealing with the physiological and metabolic criteria of Podocarpus in Egypt were reported. Thus, the objective of this work was to assess the physiological and metabolical patterns of the different species of Podocarpus; P. gracilior, P. elongates, P. macrophyllus and P. neriifolius. The highest terpenoids contents were reported in P. neriifolius, followed by P. elongatus, and P. macrophyllus. P. gracilior had the highest antioxidants amount, followed by P. macrophyllus, P. neriifolius and P. elongatus. From the GC/MS metabolic profiling, caryophyllene, β-cadinene, β-cuvebene, vitispirane, β-cadinene and amorphene were the most dominant metabolites in P. gracilior. β-Caryophyllene was the common in P. gracilior, P. elongatus, P. macrophyllus and P. neriifolius with an obvious fluctuation. The plant methanolic extracts have an obvious activity against the multidrug resistant bacteria; E. coli, P. aeruginosa, S. pyogenes and S. aureus, and fungi; A. fumigatus, A. flavus, A. niger and C. albicans in a concentration-dependent manner. The highest Taxol yield was assessed in the extracts of P. elongatus (16.4 μg/gdw), followed by P. macrophyllus, and P. neriifolius. The chemical identity of Taxol derived from P. elongatus was resolved by LC/MS, with molecular mass 854.6 m/z, and similar structural fragmentation pattern of the authentic one. The highest antitumor activity of P. elongatus extracted Taxol was assessed towards HCT-116 (30.2 μg/ml), HepG-2 (53.7 μg/ml) and MCF-7 (71.8 μg/ml). The ITS sequence of P. elongatus "as potent Taxol producer" was deposited on Genbank with accession #ON540734.1, that is the first record of Podocarpus species on Genbank.PMID:37810029 | PMC:PMC10559778 | DOI:10.1016/j.heliyon.2023.e20034

Heliyon. 2023 Sep 13;9(9):e20104. doi: 10.1016/j.heliyon.2023.e20104. eCollection 2023 Sep.ABSTRACTOBJECTIVE: This study aimed to explore the mechanism of the Bushen Huoxue Formula (BHF) in treating diminished ovarian reserve (DOR) through the use of metabolomics and integrated network pharmacology.METHODS: The study involved 24 non-pregnant female Sprague-Dawley rats, divided into four groups of six rats each: control, model, BHF, and DHEA (n = 6 per group). The model group was induced with DOR by administering Tripterygium glycosides orally [50 mg (kg·d)-1] for 14 days. Subsequently, BHF and Dehydroepiandrosterone (DHEA) treatments were given to the respective groups. Ovarian reserve function was assessed by measuring anti-Müllerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels and conducting hematoxylin-eosin staining. In addition, UHPLC-QTOF-MS analysis was performed to identify differential metabolites and pathways in DOR rats treated with BHF. In this study, LC-MS was utilized to identify the active ingredients of BHF, while network pharmacology was employed to investigate the correlations between BHF-related genes and DOR-related genes. An integrated analysis of metabonomics and network pharmacology was conducted to elucidate the mechanisms underlying the efficacy of BHF in treating DOR.RESULTS: The model group exhibited a poor general condition and a significant decrease in the number of primordial, primary, and secondary follicles (P < 0.05) when compared to the control group. However, BHF intervention resulted in an increase in the number of primordial, primary, and secondary follicles (P < 0.05), along with elevated levels of AMH and E2 (P < 0.05), and a decrease in FSH levels (P < 0.05) in DOR rats. The modeling process identified eleven classes of metabolites, including cholesterol esters (CE), diacylglycerols (DAG), hexosylceramides (HCER), lysophosphatidylcholines (LPC), phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelins (SM), ceramides (CER), free fatty acids (FFA), triacylglycerols (TAG), and lysophosphatidylethanolamines (LPE). The study found that PC, CE, DAG, and TAG are important metabolites in the treatment of DOR with BHF. LC-MS analysis showed that there were 183 active ingredients in ESI(+) mode and 51 in ESI(-) mode. Network pharmacology analysis identified 285 potential genes associated with BHF treatment for DOR in ESI(+) mode and 177 in ESI(-) mode. The combined analysis indicated that linoleic acid metabolism is the primary pathway in treating DOR with BHF.CONCLUSION: BHF was found to improve ovarian function in rats with DOR induced by Tripterygium glycosides. The study identified key metabolites such as phosphatidylcholine (PC), cholesteryl ester (CE), diacylglycerol (DAG), triacylglycerol (TAG), and the linoleic acid metabolism pathway, which were crucial in improving ovarian function in DOR rats treated with BHF.PMID:37809906 | PMC:PMC10559866 | DOI:10.1016/j.heliyon.2023.e20104

Heliyon. 2023 Sep 20;9(9):e20328. doi: 10.1016/j.heliyon.2023.e20328. eCollection 2023 Sep.ABSTRACTOBJECT: This study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1-2, as well as the potential impact of hyperuricemia (HUA) on these factors in CKD stage 1-2 patients.METHODS: In this study, fecal samples were collected from CKD stage 1-2 without HUA patients (CKD-N group), CKD stage 1-2 with HUA patients (CKD-H group), and healthy people controls (HCs group). The samples were then subjected to the microbiome (16S rRNA gene sequencing) and metabolome (liquid chromatography-tandem mass spectrometry) analyses. The multi-omics datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches.RESULTS: Gut microbial dysbiosis was found in CKD-N and CKD-H patients. At the phylum level, compared to HCs group, Bacteroidetes decreased but Proteobacteria increased in CKD-H group significantly. Fusobacteria in CKD-N group was significantly lower than HCs group. At genus level, [Eubacterium]_ventriosum_group, Fusobacterium, Agathobacter, Parabacteroides, and Roseburia significantly changed in CKD groups. [Ruminococcus]_gnavus_group was significantly lower in CKD-H group than CKD-N group. Moreover, the fecal metabolome of CKD-N and CKD-H altered significantly. d-glutamine and d-glutamate metabolism, arginine and proline metabolism, histidine metabolism, and lysine biosynthesis were down-regulated in the CKD-N group. Phenylalanine metabolism, arginine and proline metabolism, purine metabolism, and beta-alanine metabolism were up-regulated in the CKD-H group. There was a significant difference between the two CKD groups in phenylalanine metabolism. The abundance change of [Ruminococcus]_gnavus_group, [Eubacterium]_ventriosum_group, UCG-002, Alistipes, and Bifidobacterium had a close correlation with differential metabolites.CONCLUSION: The gut microbiota and metabolic status undergo significant changes in CKD patients compared to healthy people. Additionally, HUA has been found to impact the gut microbiota of CKD patients, as well as their metabolism. The close association between gut microbiota and metabolites suggests that the former plays a crucial role in metabolism.PMID:37809388 | PMC:PMC10560056 | DOI:10.1016/j.heliyon.2023.e20328

Anim Nutr. 2023 May 23;14:121-129. doi: 10.1016/j.aninu.2023.04.008. eCollection 2023 Sep.ABSTRACTThe objective of this study was to reveal the effect of rumen degradable starch (RDS) on bile acid metabolism and liver transcription in dairy goats using metabolomics and transcriptomics. Eighteen Guanzhong dairy goats of a similar weight and production level (body weight = 45.8 ± 1.54 kg, milk yield = 1.75 ± 0.08 kg, and second parity) were randomly assigned to 3 treatment groups where they were fed a low RDS (LRDS, RDS = 20.52% DM) diet, medium RDS (MRDS, RDS = 22.15% DM) diet, or high RDS (HRDS, RDS = 24.88% DM) diet, respectively. The goats were fed with the experimental diets for 5 weeks. On the last day of the experiment, all goats were anesthetized, and peripheral blood and liver tissue samples were collected. The peripheral blood samples were used in metabolomic analysis and white blood cell (WBC) count, whereas the liver tissue samples were used in transcriptomic analysis. Based on the metabolomics results, the relative abundances of primary bile acids in the peripheral blood were significantly reduced in the group that was fed the HRDS diet (P < 0.05). The WBC count was significantly increased in the HRDS group compared with that in the LRDS and MRDS groups (P < 0.01), indicating that there was inflammation in the HRDS group. Transcriptomic analysis showed that 4 genes related to bile acid secretion (genes: MDR1, RXRα, AE2, SULT2A1) were significantly downregulated in the HRDS group. In addition, genes related to the immune response were upregulated in the HRDS group, suggesting the HRDS diet induced a hepatic inflammatory response mediated by lipopolysaccharides (LPS) (gene: LBP), activated the Toll-like receptor 4 binding (genes: S100A8, S100A9) and the NF-kappa B signaling pathway (genes: LOC106503980, LOC108638497, CD40, LOC102180880, LOC102170970, LOC102175177, LBP, LOC102168903, LOC102185461, LY96 and CXCL8), triggered inflammation and complement responses (genes: C1QB, C1QC, and CFD). The HRDS diet induced a hepatic inflammatory response may be mediated by activating the Toll-like receptor 4 binding and NF-kappa B signaling pathway after free LPS entered the liver. The changes of bile acids profile in blood and the down-regulation of 4 key genes (MDR1, RXRα, AE2, SULT2A1) involved in bile secretion in liver are probably related to liver inflammation.PMID:37808950 | PMC:PMC10556040 | DOI:10.1016/j.aninu.2023.04.008

bioRxiv. 2023 Sep 26:2023.09.25.559407. doi: 10.1101/2023.09.25.559407. Preprint.ABSTRACTBile acids (BAs) are cholesterol-derived molecules in the human gut that aid in digestion and nutrient absorption, regulate host metabolic processes, and influence gut microbiome composition. Both the host and its microbiome contribute to enzymatic modifications that shape the chemical diversity of BAs in the gut. Several bacterial species have been reported to conjugate standard amino acids to BAs, but it was not known if bacteria conjugate other classes of amines to BAs. We show that Bacteroides fragilis strain P207, isolated from a bacterial bloom in the J-pouch of a patient with ulcerative colitis (UC) pouchitis, conjugates standard amino acids and the neuroactive amines γ-aminobutyric acid (GABA) and tyramine to deoxycholic acid. We extended our analysis to other human gut isolates and identified bacterial species that conjugate GABA and tyramine to primary and secondary BAs, and further identified diverse BA-GABA and -tyramine amides in human stool. A time-series metabolomic analysis of UC J-pouch contents revealed a lack of secondary bile acids and a shifting BA conjugate profile before, during and after onset of pouchitis, including temporal changes in several BA-GABA amides. Treatment of pouchitis with ciprofloxacin was associated with a marked reduction of nearly all BA amides in the J-pouch. Our study expands the known repertoire of conjugated bile acids produced by bacteria to include BA conjugates to the neuroactive amines GABA and tyramine, and demonstrates that these molecules are present in the human gut.IMPORTANCE: Bile acids (BAs) are modified in multiple ways by host enzymes and the microbiota to produce a chemically diverse set of molecules that assist in the digestive process and impact many physiological functions. This study reports the discovery of bacterial species that conjugate the neuroactive molecules, GABA and tyramine, to primary and secondary BAs. We further present evidence that BA-GABA and BA-tyramine conjugates are present in the human gut, and document a shifting BA-GABA profile in a human pouchitis patient before, during and after inflammation and antibiotic treatment. GABA and tyramine are potent neuroactive molecules and common metabolic products of the gut microbiota. GABA- and tyramine-conjugated BAs may influence receptor-mediated regulatory mechanisms within the gastrointestinal tract and absorption of these molecules and their entry into the enterohepatic circulation may impact host physiology at distal tissue sites. This discovery defines new conjugated bile acids in the human gut.PMID:37808758 | PMC:PMC10557584 | DOI:10.1101/2023.09.25.559407

bioRxiv. 2023 Sep 27:2023.09.26.559021. doi: 10.1101/2023.09.26.559021. Preprint.ABSTRACTGenomic studies of molecular traits have provided mechanistic insights into complex disease, though these lag behind for brain-related traits due to the inaccessibility of brain tissue. We leveraged cerebrospinal fluid (CSF) to study neurobiological mechanisms in vivo , measuring 5,543 CSF metabolites, the largest panel in CSF to date, in 977 individuals of European ancestry. Individuals originated from two separate cohorts including cognitively healthy subjects (n=490) and a well-characterized memory clinic sample, the Amsterdam Dementia Cohort (ADC, n=487). We performed metabolite quantitative trait loci (mQTL) mapping on CSF metabolomics and found 126 significant mQTLs, representing 65 unique CSF metabolites across 51 independent loci. To better understand the role of CSF mQTLs in brain-related disorders, we performed a metabolome-wide association study (MWAS), identifying 40 associations between CSF metabolites and brain traits. Similarly, over 90% of significant mQTLs demonstrated colocalized associations with brain-specific gene expression, unveiling potential neurobiological pathways.PMID:37808647 | PMC:PMC10557608 | DOI:10.1101/2023.09.26.559021

Front Microbiol. 2023 Sep 21;14:1254728. doi: 10.3389/fmicb.2023.1254728. eCollection 2023.ABSTRACTDespite the introduction of effective treatments for hepatitis C in clinics, issues remain regarding the liver disease induced by chronic hepatitis C virus (HCV) infection. HCV is known to disturb the metabolism of infected cells, especially lipid metabolism and redox balance, but the mechanisms leading to HCV-induced pathogenesis are still poorly understood. In an APEX2-based proximity biotinylation screen, we identified ACBD5, a peroxisome membrane protein, as located in the vicinity of HCV replication complexes. Confocal microscopy confirmed the relocation of peroxisomes near HCV replication complexes and indicated that their morphology and number are altered in approximately 30% of infected Huh-7 cells. Peroxisomes are small versatile organelles involved among other functions in lipid metabolism and ROS regulation. To determine their importance in the HCV life cycle, we generated Huh-7 cells devoid of peroxisomes by inactivating the PEX5 and PEX3 genes using CRISPR/Cas9 and found that the absence of peroxisomes had no impact on replication kinetics or infectious titers of HCV strains JFH1 and DBN3a. The impact of HCV on peroxisomal functions was assessed using sub-genomic replicons. An increase of ROS was measured in peroxisomes of replicon-containing cells, correlated with a significant decrease of catalase activity with the DBN3a strain. In contrast, HCV replication had little to no impact on cytoplasmic and mitochondrial ROS, suggesting that the redox balance of peroxisomes is specifically impaired in cells replicating HCV. Our study provides evidence that peroxisome function and morphology are altered in HCV-infected cells.PMID:37808318 | PMC:PMC10551450 | DOI:10.3389/fmicb.2023.1254728

J Food Sci. 2023 Oct 8. doi: 10.1111/1750-3841.16761. Online ahead of print.ABSTRACTThe effects of aging and microbial growth on the metabolome of aged beef were investigated in this study. The metabolome of beef is influenced by the aging method applied. This includes the aging-related changes in metabolism and the presence of microorganisms on the beef during aging that may affect the beef and its quality. The inner part and the trimmed surface of dry-aged (the surface of dry-aged beef is also called the "crust" due to its drying during aging) and wet-aged beef were analyzed by 1 H nuclear magnetic resonance (NMR) spectroscopy over aging periods up to 28 days at intervals of 7 days, and the former also by microbiological analysis. The metabolome detected by 1 H NMR spectroscopy demonstrated changes over the aging time of beef and differed depending on the sampling location (surface or inner part of beef). The influence of the microbiota on changes in the metabolome can be negligible due to the low microbial growth on the surface of dry-aged beef (<3 log CFU/g). Therefore, the aging-related metabolism postmortem of the analyzed dry-aged beef might be the main factor for metabolic changes. The significantly (p < 0.05) higher amino acids and inosine concentrations and lower inosine 5'-monophosphate concentrations suggested enhanced protein degradation and energy metabolism in the wet-aged beef compared to the dry-aged beef, probably due to the combined influence of the aging and the microbiota on the wet-aged beef and, thus, its metabolic changes.PMID:37807472 | DOI:10.1111/1750-3841.16761