PubMed

Viruses. 2024 Jun 29;16(7):1054. doi: 10.3390/v16071054.ABSTRACTThe gut microbiota is involved in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), but few studies have focused on the role of the gut virome in IBS-D. We aimed to explore the characteristics of the gut virome in patients with IBS-D, its interactions with bacteria and metabolites, and the associations between gut multiomics profiles and symptoms. This study enrolled twelve patients with IBS-D and eight healthy controls (HCs). The stool samples were subjected to metavirome sequencing, 16S rRNA gene sequencing, and untargeted metabolomic analysis. The participants completed relevant scales to assess the severity of their gastrointestinal symptoms, depression, and anxiety. The results revealed unique DNA and RNA virome profiles in patients with IBS-D with significant alterations in the abundance of contigs from Siphoviridae, Podoviridae, Microviridae, Picobirnaviridae, and Tombusviridae. Single-omics co-occurrence network analyses demonstrated distinct differences in the gut virus, bacteria, and metabolite network patterns between patients with IBS-D and HCs. Multiomics networks revealed that short-chain fatty acid-producing bacteria occupied more core positions in IBS-D networks, but had fewer links to viruses. Amino acids and their derivatives exhibit unique connectivity patterns and centrality features within the IBS-D network. The gastrointestinal and psychological symptom factors of patients with IBS-D were highly clustered in the symptom-multiomics network compared with those of HCs. Machine learning models based on multiomics data can distinguish IBS-D patients from HCs and predict the scores of gastrointestinal and psychological symptoms. This study provides insights into the interactions among gut viruses, bacteria, metabolites, and clinical symptoms in patients with IBS-D, indicating further classification and personalized treatment for IBS-D.PMID:39066219 | DOI:10.3390/v16071054

Pharmaceuticals (Basel). 2024 Jul 5;17(7):895. doi: 10.3390/ph17070895.ABSTRACTInulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD.PMID:39065745 | DOI:10.3390/ph17070895

Pharmaceuticals (Basel). 2024 Jul 4;17(7):890. doi: 10.3390/ph17070890.ABSTRACTPanama boasts an expansive mangrove area and stands as one of the most biodiverse countries in America. While mangrove plants have long been utilized in traditional medicine, there are still unstudied species whose potential medicinal applications remain unknown. This study aimed to extract bioactive compounds from Mora oleifera (Triana ex Hemsl.) Ducke, an understudied mangrove species. Through bioassay-guided fractionation of the crude extract, we isolated seven active compounds identified as lupenone (1), lupeol (2), α-amyrin (3), β-amyrin (4), palmitic acid (5), sitosterol (6), and stigmasterol (7). Compound structures were determined using spectroscopic analyses, including APCI-HR-MS and NMR. Compounds 1-7 displayed concentration-dependent inhibition of the alpha-glucosidase enzyme, with IC50 values of 0.72, 1.05, 2.13, 1.22, 240.20, 18.70, and 163.10 µM, respectively. Their inhibitory activity surpassed acarbose, the positive control (IC50 241.6 µM). Kinetic analysis revealed that all compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bonded to the same site as acarbose in human intestinal alpha-glucosidase (PDB: 3TOP). A complementary metabolomic analysis of M. oleifera active fractions revealed the presence of 64 compounds, shedding new light on the plant's chemical composition. These findings suggest that M. oleifera holds promise as a valuable botanical source for developing compounds for managing blood sugar levels in individuals with diabetes.PMID:39065741 | DOI:10.3390/ph17070890

Pharmaceuticals (Basel). 2024 Jun 22;17(7):821. doi: 10.3390/ph17070821.ABSTRACTThe expected progress in SARS-CoV-2 vaccinations, as anticipated in 2020 and 2021, has fallen short, exacerbating global disparities due to a lack of universally recognized "safe and effective" vaccines. This study focuses on extracts of South African medicinal plants, Artemisia annua and Artemisia afra, to identify metabolomic bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors. The extracts were monitored for cytotoxicity using a resazurin cell viability assay and xCELLigence real-time cell analyzer. Chemical profiling was performed using UPLC-MS/MS, orthogonal projection to latent structures (OPLS), and evaluated using principle component analysis (PCA) models. Identified bioactive compounds were subjected to in vitro SARS-CoV-2 enzyme inhibition assay using standard methods and docked into the spike (S) glycoprotein of SARS-CoV-2 using Schrodinger® suite followed by molecular dynamics simulation studies. Cell viability assays revealed non-toxic effects of extracts on HEK293T cells at lower concentrations. Chemical profiling identified 81 bioactive compounds, with compounds like 6″-O-acetylglycitin, 25-hydroxyvitamin D3-26,23-lactone, and sesaminol glucoside showing promising binding affinity. Molecular dynamics simulations suggested less stable binding, but in vitro studies demonstrated the ability of these compounds to interfere with SARS-CoV-2 spike protein's binding to the human ACE2 receptor. Sesaminol glucoside emerged as the most effective inhibitor against this interaction. This study emphasizes the importance of multiplatform metabolite profiling and chemometrics to understand plant extract composition. This finding is of immense significance in terms of unravelling metabolomics bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors and holds promise for phytotherapeutics against SARS-CoV-2.PMID:39065672 | DOI:10.3390/ph17070821

Pharmaceutics. 2024 Jul 11;16(7):927. doi: 10.3390/pharmaceutics16070927.ABSTRACTMost clinical isolates of both Staphylococcus aureus and Staphylococcus epidermidis show the capacity to adhere to abiotic surfaces and to develop biofilms resulting in a contribution to chronic human skin infections. Antibiotic resistance and poor biofilm penetration are the main causes of ineffective therapeutic treatment in killing bacteria within biofilms. A possible strategy could be represented by drug delivery systems, such as nanoemulsions (composed of bioactive oil, surfactant and water phase), which are useful for enhancing the drug permeation of a loaded drug inside the biofilm and its activity. Phytochemical characterization of Pistacia lentiscus oil (LO) by direct infusion Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) allowed the identification of bioactive compounds with antimicrobial properties, including fatty acids and phenolic compounds. Several monoterpenes and sesquiterpenes have been also detected and confirmed by gas chromatography-mass spectrometric (GC-MS) analysis, together providing a complete metabolomic profiling of LO. In the present study, a nanoemulsion composed of LO has been employed for improving Levofloxacin water solubility. A deep physical-chemical characterization of the nanoemulsion including hydrodynamic diameter, ζ-potential, morphology, entrapment efficiency, stability release and permeation studies was performed. Additionally, the antimicrobial/antibiofilm activity of these preparations was evaluated against reference and clinical Staphylococcus spp. strains. In comparison to the free-form antibiotic, the loaded NE nanocarriers exhibited enhanced antimicrobial activity against the sessile forms of Staphylococcus spp. strains.PMID:39065624 | DOI:10.3390/pharmaceutics16070927

Pharmaceutics. 2024 Jul 9;16(7):916. doi: 10.3390/pharmaceutics16070916.ABSTRACT(1) Background: Salix species occurring in Finland have not been well studied for their antimicrobial potential, despite their frequent use for lung and stomach problems in traditional medicine. Thus, twig extracts of three species of Salix that are found naturally in Finland and one cultivated species were screened for their antimicrobial properties against human pathogenic bacteria. S. starkeana and S. x pendulina were screened for antibacterial effects for the first time. (2) Methods: An agar diffusion and a microplate method were used for the screenings. Time-kill effects were measured using a plate-count and a microplate method. A DPPH-method using a qualitative TLC-analysis was used to detect antioxidant compounds in antimicrobial extracts. Metabolites from a S. myrsinifolia extract showing good antibacterial effects were identified using UPLC/QTOF-MS. (3) Results: A methanol extract of S. starkeana was particularly active against B. cereus (MIC 625 µg/mL), and a methanol extract of S. myrsinifolia showed good activity against S. aureus and B. cereus (MIC 1250 µg/mL) and showed bactericidal effects during a 24 h incubation of B. cereus. Moreover, a decoction of S. myrsinifolia resulted in good growth inhibition against P. aeruginosa. Our UPLC/QTOF-MS results indicated that proanthocyanidins (PAs), and especially the dimer procyanidin B1 (m/z 577) and other procyanidin derivatives, including highly polymerized proanthocyanidins, were abundant in S. myrsinifolia methanol extracts. Procyanidin B1 and its monomer catechin, as well as taxifolin and p-hydroxycinnamic acid, all present in S. myrsinifolia twigs, effectively inhibited B. cereus (MIC 250 µg/mL). (4) Conclusions: This study indicates that Finnish Salix species contain an abundance of antibacterial condensed tannins, phenolic acids and other polyphenols that deserve further research for the antibacterial mechanisms of action.PMID:39065613 | DOI:10.3390/pharmaceutics16070916

Plants (Basel). 2024 Jul 22;13(14):2005. doi: 10.3390/plants13142005.ABSTRACTFusarium oxysporum f. sp. lentis (Fol) is considered the most destructive disease for lentil (Lens culinaris Medik.) worldwide. Despite the extensive studies elucidating plants' metabolic response to fungal agents, there is a knowledge gap in the biochemical mechanisms governing Fol-resistance in lentil. Τhis study aimed at comparatively evaluating the metabolic response of two lentil genotypes, with contrasting phenotypes for Fol-resistance, to Fol-inoculation. Apart from gaining insights into the metabolic reprogramming in response to Fol-inoculation, the study focused on discovering novel biomarkers to improve early selection for Fol-resistance. GC-MS-mediated metabolic profiling of leaves and roots was employed to monitor changes across genotypes and treatments as well as their interaction. In total, the analysis yielded 178 quantifiable compounds, of which the vast majority belonged to the groups of carbohydrates, amino acids, polyols and organic acids. Despite the magnitude of metabolic fluctuations in response to Fol-inoculation in both genotypes under study, significant alterations were noted in the content of 18 compounds, of which 10 and 8 compounds referred to roots and shoots, respectively. Overall data underline the crucial contribution of palatinitol and L-proline in the metabolic response of roots and shoots, respectively, thus offering possibilities for their exploitation as metabolic biomarkers for Fol-resistance in lentil. To the best of our knowledge, this is the first metabolomics-based approach to unraveling the effects of Fol-inoculation on lentil's metabolome, thus providing crucial information related to key aspects of lentil-Fol interaction. Future investigations in metabolic aspects of lentil-Fol interactions will undoubtedly revolutionize the search for metabolites underlying Fol-resistance, thus paving the way towards upgrading breeding efforts to combat fusarium wilt in lentil.PMID:39065530 | DOI:10.3390/plants13142005

Plants (Basel). 2024 Jul 14;13(14):1935. doi: 10.3390/plants13141935.ABSTRACTLycium barbarum has been widely planted in arid and semi-arid areas due to its drought-resistant ability, which is of great economic value as a medicinal and edible homology plant. In this study, the metabolome of the L. barbarum variety "Ningqi 7" under different drought stress conditions was compared and analyzed by the non-targeted UPLC-MS (ultra-high performance liquid chromatography with mass spectrometry) technique. The results showed that drought stress significantly decreased the water content of leaves, increased the activity of antioxidant enzymes in plants, and up-regulated the metabolites and pathways involved in osmoregulation, antioxidant stress, energy metabolism, and signal transduction. Under moderate drought (40-45% FC), L. barbarum accumulated osmoregulatory substances mainly through the up-regulation of the arginine metabolism pathway. At the same time, phenylalanine metabolism and cutin, suberine, and wax biosynthesis were enhanced to improve the antioxidant capacity and reduce water loss. However, in severe drought (10-15% FC), L. barbarum shifted to up-regulate purine metabolism and lysine degradation and redistributed energy and nitrogen resources. In addition, vitamin B6 metabolism was significantly upregulated in both groups of stress levels, playing a key role in antioxidant and growth regulation. These observations delineate the metabolic adaptations of L. barbarum "Ningqi 7" in response to drought stress.PMID:39065462 | DOI:10.3390/plants13141935

Plants (Basel). 2024 Jul 12;13(14):1928. doi: 10.3390/plants13141928.ABSTRACTRed palm weevil (RPW) (Rhynchophorus ferrugineus) threatens most palm species worldwide. This study investigated the molecular responses of coconut (Cocos nucifera) leaves to RPW infestation through metabolomics and transcriptomics analysis. An RPW insect attack model was developed by placing different RPW larval densitiesin coconut plants and measuring the relative chlorophyll content of different leaf positions and physiological indicators of dysfunction after RPW infestation. The metabolomic changes were detected in the leaves of 10, 20, 30, 40, and 50 days after infestation (DAI) using GC-MS. Certain metabolites (glycine, D-pinitol, lauric acid, allylmalonic acid, D-glucaro-1, 4-lactone, protocatechuic acid, alpha, and alpha-trehalose) were found to be possible indicators for distinct stages of infestation using metabolomics analysis. The influence on ABC transporters, glutathione, galactose, and glycolipid metabolism was emphasized by pathway analysis. Differentially expressed genes (DEGs) were identified at 5, 10, 15, and 20 DAI through transcriptomics analysis of infested coconut leaves, with altered expression levels under RPW infestation. The KEGG pathway and GO analysis revealed enrichment in pathways related to metabolism, stress response, and plant-pathogen interactions, shedding light on the intricate mechanisms underlying coconut-RPW interactions. The identified genes may serve as potential markers for tracking RPW infestation progression and could inform strategies for pest control and management.PMID:39065455 | DOI:10.3390/plants13141928

Plants (Basel). 2024 Jul 12;13(14):1925. doi: 10.3390/plants13141925.ABSTRACTSome citrus orchards in China often experience nitrogen (N) deficiency. For the first time, targeted metabolomics was used to examine N-deficient effects on hormones in sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) leaves and roots. The purpose was to validate the hypothesis that hormones play a role in N deficiency tolerance by regulating root/shoot dry weight ratio (R/S), root system architecture (RSA), and leaf and root senescence. N deficiency-induced decreases in gibberellins and indole-3-acetic acid (IAA) levels and increases in cis(+)-12-oxophytodienoic acid (OPDA) levels, ethylene production, and salicylic acid (SA) biosynthesis might contribute to reduced growth and accelerated senescence in leaves. The increased ethylene formation in N-deficient leaves might be caused by increased 1-aminocyclopropanecarboxylic acid and OPDA and decreased abscisic acid (ABA). N deficiency increased R/S, altered RSA, and delayed root senescence by lowering cytokinins, jasmonic acid, OPDA, and ABA levels and ethylene and SA biosynthesis, increasing 5-deoxystrigol levels, and maintaining IAA and gibberellin homeostasis. The unchanged IAA concentration in N-deficient roots involved increased leaf-to-root IAA transport. The different responses of leaf and root hormones to N deficiency might be involved in the regulation of R/S, RSA, and leaf and root senescence, thus improving N use efficiency, N remobilization efficiency, and the ability to acquire N, and hence conferring N deficiency tolerance.PMID:39065452 | DOI:10.3390/plants13141925

Plants (Basel). 2024 Jul 9;13(14):1885. doi: 10.3390/plants13141885.ABSTRACTSoybean (Glycine max) and mung bean (Vigna radiata) are key legumes with global importance, but their mechanisms for coping with cold stress-a major challenge in agriculture-have not been thoroughly investigated, especially in a comparative study. This research aimed to fill this gap by examining how these two major legumes respond differently to cold stress and exploring the role of uniconazole, a potential stress mitigator. Our comprehensive approach involved transcriptomic and metabolomic analyses, revealing distinct responses between soybean and mung bean under cold stress conditions. Notably, uniconazole was found to significantly enhance cold tolerance in mung bean by upregulating genes associated with photosynthesis, while its impact on soybean was either negligible or adverse. To further understand the molecular interactions, we utilized advanced machine learning algorithms for protein structure prediction, focusing on photosynthetic pathways. This enabled us to identify LOC106780309 as a direct binding target for uniconazole, confirmed through isothermal titration calorimetry. This research establishes a new comparative approach to explore how soybean and mung bean adapt to cold stress, offers key insights to improve the hardiness of legumes against environmental challenges, and contributes to sustainable agricultural practices and food security.PMID:39065416 | DOI:10.3390/plants13141885

Microorganisms. 2024 Jul 15;12(7):1432. doi: 10.3390/microorganisms12071432.ABSTRACTLevodopa is the mainstay of treatments for Parkinson's disease (PD), but large heterogeneity exists in patient response. Increasing evidence implicates bile acids (BAs) involved in the pathogenesis of PD. Furthermore, BAs have also participated in drug bioavailability. However, the impact of BAs on levodopa response (LR) has not been investigated. This study evaluated the association between fecal BAs and LR. Levodopa challenge test (LCT) was conducted in 92 PD patients to assess LR. A total of 36 fecal BAs and plasma levodopa concentrations were detected using LC-MS/MS. The difference of BAs between subgroups with bottom and top 30% LR were analyzed and fecal samples from the two groups were collected for metagenomic shotgun analysis. No fecal BAs were significantly correlated with LR, except for chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3-β-glucuronide, R = -0.228, p-value = 0.039). We found no significant difference in BAs between subgroups with bottom and top 30% LR. What is more, no significant changes in bacterial species composition related to bile acids metabolism or in the proportional representation of genes encoding known bile acids enzymes were observed between the groups. Overall, our data do not support an association between fecal BAs and levodopa response in PD patients. More precise macro-metabolomic approaches are needed to reveal the potential association between gut microbial interactions and the treatment effect of levodopa.PMID:39065200 | DOI:10.3390/microorganisms12071432

Microorganisms. 2024 Jul 12;12(7):1415. doi: 10.3390/microorganisms12071415.ABSTRACTSepsis is a life-threatening condition arising from a dysregulated host immune response to infection, leading to a substantial global health burden. The accurate identification of bacterial pathogens in sepsis is essential for guiding effective antimicrobial therapy and optimising patient outcomes. Traditional culture-based bacterial typing methods present inherent limitations, necessitating the exploration of alternative diagnostic approaches. This study reports the successful application of Fourier-transform infrared (FT-IR) spectroscopy in combination with chemometrics as a potent tool for the classification and discrimination of microbial species and strains, primarily sourced from individuals with invasive infections. These samples were obtained from various children with suspected sepsis infections with bacteria and fungi originating at different sites. We conducted a comprehensive analysis utilising 212 isolates from 14 distinct genera, comprising 202 bacterial and 10 fungal isolates. With the spectral analysis taking several weeks, we present the incorporation of quality control samples to mitigate potential variations that may arise between different sample plates, especially when dealing with a large sample size. The results demonstrated a remarkable consistency in clustering patterns among 14 genera when subjected to principal component analysis (PCA). Particularly, Candida, a fungal genus, was distinctly recovered away from bacterial samples. Principal component discriminant function analysis (PC-DFA) allowed for distinct discrimination between different bacterial groups, particularly Gram-negative and Gram-positive bacteria. Clear differentiation was also observed between coagulase-negative staphylococci (CNS) and Staphylococcus aureus isolates, while methicillin-resistant S. aureus (MRSA) was also separated from methicillin-susceptible S. aureus (MSSA) isolates. Furthermore, highly accurate discrimination was achieved between Enterococcus and vancomycin-resistant enterococci isolates with 98.4% accuracy using partial least squares-discriminant analysis. The study also demonstrates the specificity of FT-IR, as it effectively discriminates between individual isolates of Streptococcus and Candida at their respective species levels. The findings of this study establish a strong groundwork for the broader implementation of FT-IR and chemometrics in clinical and microbiological applications. The potential of these techniques for enhanced microbial classification holds significant promise in the diagnosis and management of invasive bacterial infections, thereby contributing to improved patient outcomes.PMID:39065183 | DOI:10.3390/microorganisms12071415

Microorganisms. 2024 Jul 12;12(7):1410. doi: 10.3390/microorganisms12071410.ABSTRACTProbiotics play an important role in animal production, providing health benefits to the host by improving intestinal microbial balance. In this study, we added three different probiotics, Saccharomyces cerevisiae (SC), Bacillus licheniformis (BL), and lactic acid bacteria (LAB), and compared them with the control group (CON), to investigate the effects of probiotic supplementation on growth performance, gut microbiology, and gut flora of S. trutta. Our results showed that feeding probiotics improved the survival, growth, development, and fattening of S. trutta. Additionally, probiotic treatment causes changes in the gut probiotic community, and the gut flora microorganisms that cause significant changes vary among the probiotic treatments. However, in all three groups, the abundance of Pseudomonas, Acinetobacter, and Rhizophagus bacterial genera was similar to that in the top three comparative controls. Furthermore, differences in the composition of intestinal microbiota among feed types were directly associated with significant changes in the metabolomic landscape, including lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. The probiotic treatment altered the gut microbiome, gut metabolome, and growth performance of S. trutta. Using a multi-omics approach, we discovered that the addition of probiotics altered the composition of gut microbiota, potentially leading to modifications in gut function and host phenotype. Overall, our results highlight the importance of probiotics as a key factor in animal health and productivity, enabling us to better evaluate the functional potential of probiotics.PMID:39065178 | DOI:10.3390/microorganisms12071410

Microorganisms. 2024 Jul 4;12(7):1369. doi: 10.3390/microorganisms12071369.ABSTRACTGestational diabetes mellitus (GDM) triggers alterations in the maternal microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. We investigated maternal microbiome-metabolomic changes, including over 600 metabolites from a subset of the "Choosing Healthy Options in Carbohydrate Energy" (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n = 18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n = 16, 40% carbohydrate/45% fat/15% protein). All meals were provided. Diets were eucaloric, and fiber content was similar. CHOICE was associated with increases in trimethylamine N-oxide, indoxyl sulfate, and several triglycerides, while CONV was associated with hippuric acid, betaine, and indole propionic acid, suggestive of a healthier metabolome. Conversely, the microbiome of CHOICE participants was enriched with carbohydrate metabolizing genes and beneficial taxa such as Bifidobacterium adolescentis, while CONV was associated with inflammatory pathways including antimicrobial resistance and lipopolysaccharide biosynthesis. We also identified latent metabolic groups not associated with diet: a metabolome associated with less of a decrease in fasting glucose, and another associated with relatively higher fasting triglycerides. Our results suggest that GDM diets produce specific microbial and metabolic responses during pregnancy, while host factors also play a role in triglycerides and glucose metabolism.PMID:39065137 | DOI:10.3390/microorganisms12071369

Microorganisms. 2024 Jun 28;12(7):1319. doi: 10.3390/microorganisms12071319.ABSTRACTPatients with colorectal cancer (CRC) have a high prevalence of iron deficiency anemia (IDA), and the gut microbiota is closely related to iron metabolism. We performed metagenomic and metabolomic analyses of stool samples from 558 eligible samples, including IDA CRC patients (IDA, n = 69), non-anemia CRC patients (Non-Anemia, n = 245), and healthy controls (CTRL, n = 244), to explore the dynamically altered gut microbes and their metabolites. Compared with the CTRL group, fecal bacteria in both the IDA group and the Non-Anemia group showed a decrease in alpha diversity and changes in microbial communities. Flavonifractor plautii (F. plautii) increases progressively from CTRL to Non-Anemia to IDA, accompanied by decreased trimethoxyflavanone and a downregulated KO gene, megDIII. In the Non-Anemia group, Parabacteroides showed a specifically elevated abundance positively correlated with enriched 1,25-dihydroxyvitamin D3. The intricate correlations among gut microbiota, metabolites, and KO genes were uncovered and highlighted, implicating an aberrant iron metabolism vulnerable to chronic inflammation during the deterioration of the anemic condition. Furthermore, the amount of F. plautii in feces achieved independent and effective prediction performance for the poor outcome of CRC. Perturbed host-microbe interplays represent a novel prospect for explaining the pathogenesis of CRC-associated IDA. The fecal microbial features also reflect the associations between IDA and elevated CRC recurrence risk.PMID:39065088 | DOI:10.3390/microorganisms12071319

Molecules. 2024 Jul 17;29(14):3346. doi: 10.3390/molecules29143346.ABSTRACTPeucedanum decursivum (Miq.) Maxim (P. decursivum) is a traditional Chinese medicinal plant with pharmacological effects such as anti-inflammatory and anti-tumor effects, the root of which is widely used as medicine. Determining the spatial distribution and pharmacological mechanisms of metabolites is necessary when studying the effective substances of medicinal plants. As a means of obtaining spatial distribution information of metabolites, mass spectrometry imaging has high sensitivity and allows for molecule visualization. In this study, matrix-assisted laser desorption mass spectrometry (MALDI-TOF-MSI) and network pharmacology were used for the first time to visually study the spatial distribution and anti-inflammatory mechanism of coumarins, which are metabolites of P. decursivum, to determine their tissue localization and mechanism of action. A total of 27 coumarins were identified by MALDI-TOF-MSI, which mainly concentrated in the cortex, periderm, and phloem of the root of P. decursivum. Network pharmacology studies have identified key targets for the anti-inflammatory effect of P. decursivum, such as TNF, PTGS2, and PRAKA. GO enrichment and KEGG pathway analyses indicated that coumarins in P. decursivum mainly participated in biological processes such as inflammatory response, positive regulation of protein kinase B signaling, chemical carcinogenesis receptor activation, pathways in cancer, and other biological pathways. The molecular docking results indicated that there was good binding between components and targets. This study provides a basis for understanding the spatial distribution and anti-inflammatory mechanism of coumarins in P. decursivum.PMID:39064924 | DOI:10.3390/molecules29143346

Nutrients. 2024 Jul 22;16(14):2368. doi: 10.3390/nu16142368.ABSTRACT(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism. Here, we investigated the effects of oral PA supplementation on the human serum metabolome and analyzed changes in the serum metabolome in relation to the cholesterol-lowering properties of PA. (2) Methods: The serum metabolome of patients supplemented with either placebo or propionate orally for 8 weeks was assessed using a combination of flow injection analysis-tandem (FIA-MS/MS) as well as liquid chromatography (LC-MS/MS) and mass spectrometry using a targeted metabolomics kit (MxP®Quant 500 kit: BIOCRATES Life Sciences AG, Innsbruck, Austria). A total of 431 metabolites were employed for further investigation in this study. (3) Results: We observed a significant increase in distinct bile acids (GCDCA: fold change = 1.41, DCA: fold change = 1.39, GUDCA: fold change = 1.51) following PA supplementation over the study period, with the secondary bile acid DCA displaying a significant negative correlation with the serum cholesterol levels. (4) Conclusions: Oral supplementation with PA modulates the serum metabolome with a particular impact on the circulatory bile acid profile. Since cholesterol and bile acid metabolism are interconnected, the elevation of the secondary bile acid DCA may contribute to the cholesterol-lowering effect of PA.PMID:39064811 | DOI:10.3390/nu16142368

Nutrients. 2024 Jul 20;16(14):2346. doi: 10.3390/nu16142346.ABSTRACTDiabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.PMID:39064789 | DOI:10.3390/nu16142346

Nutrients. 2024 Jul 19;16(14):2341. doi: 10.3390/nu16142341.ABSTRACT(1) Background: The diversity of blood biomarkers used to assess the metabolic mechanisms of hydrogen limits a comprehensive understanding of its effects on improving exercise performance. This study evaluated the impact of hydrogen-rich gas (HRG) on metabolites following sprint-interval exercise using metabolomics approaches, aiming to elucidate its underlying mechanisms of action. (2) Methods: Ten healthy adult males participated in the Wingate Sprint-interval test (SIT) following 60 min of HRG or placebo (air) inhalation. Venous blood samples were collected for metabolomic analysis both before and after gas inhalation and subsequent to completing the SIT. (3) Results: Compared with the placebo, HRG inhalation significantly improved mean power, fatigue index, and time to peak for the fourth sprint and significantly reduced the attenuation values of peak power, mean power, and time to peak between the first and fourth. Metabolomic analysis highlighted the significant upregulation of acetylcarnitine, propionyl-L-carnitine, hypoxanthine, and xanthine upon HRG inhalation, with enrichment pathway analysis suggesting that HRG may foster fat mobilization by enhancing coenzyme A synthesis, promoting glycerophospholipid metabolism, and suppressing insulin levels. (4) Conclusions: Inhaling HRG before an SIT enhances end-stage anaerobic sprint capabilities and mitigates fatigue. Metabolomic analysis suggests that HRG may enhance ATP recovery during interval stages by accelerating fat oxidation, providing increased energy replenishment for late-stage sprints.PMID:39064785 | DOI:10.3390/nu16142341