PubMed

J Agric Food Chem. 2024 Oct 23. doi: 10.1021/acs.jafc.4c07127. Online ahead of print.ABSTRACTTerpenoids are important secondary metabolites in Rubus. Rubusoside is a relatively specific diterpenoid bioactive component in the leaves of Chinese Sweet Tea (Rubus suavissimus). However, the terpenoid anabolic pathway of Rubus and the molecular mechanism underlying the specific accumulation of rubusoside in R. suavissimus remain unclear. Here, metabolomics and transcriptomics analyses were performed on differences in terpenoid metabolism levels between R. suavissimus (sweet leaves) and Rubus chingii (bitter leaves). Steviol glycosides and goshonosides primarily accumulated in R. suavissimus and R. chingii, respectively. Three pairs of highly homologous glycosyltransferase genes (UGT85A57, UGT75L20, and UGT75T4) associated with rubusoside biosynthesis in the two Rubus species were identified. The three pairs of UGT proteins in both species could glycosylate steviol. Thus, the transcriptional regulation of UGTs in R. suavissimus appears to play a pivotal role in rubusoside accumulation. Our findings provide insights into the differences in terpenoid metabolism between R. suavissimus and R. chingii and reveal the molecular mechanism of rubusoside accumulation in R. suavissimus.PMID:39442010 | DOI:10.1021/acs.jafc.4c07127

Blood. 2024 Oct 23:blood.2024025366. doi: 10.1182/blood.2024025366. Online ahead of print.ABSTRACTAntibiotic-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapies. In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes. In a discovery subset of these patients (n=67), we found that the use of these ABX was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n=58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery n=40, validation n=28). These findings were recapitulated in an immune-competent CAR-T mouse model, where meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-T cells, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T cell efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy.PMID:39441941 | DOI:10.1182/blood.2024025366

J Cancer Res Clin Oncol. 2024 Oct 23;150(10):471. doi: 10.1007/s00432-024-05990-1.ABSTRACTThe incidence of brain tumors among children is second only to acute lymphoblastic leukemia, but the mortality rate of brain tumors has exceeded that of leukemia, making it the most common cause of death among children. Medulloblastoma (MB) is the most common type of brain tumor among children. Malignant brain tumors have strong invasion and metastasis capabilities, can spread through cerebrospinal fluid, and have a high mortality rate. In 2010, the World Health Organization first divided MB into four molecular subtypes based on molecular markers: WNT, Sonic hedgehog (SHH), Group 3, and Group 4. MB is a highly heterogeneous tumor. Different molecular subtypes of MB have significantly different clinical, pathological, and molecular characteristics. The prognosis of MB varies significantly among patients with different subtypes of this cancer. Thus, it is needed to study new diagnostic and therapeutic strategies. Metabolomics is an advanced analytical technology that uses various spectroscopic, electrochemical, and data analysis technologies to study and analyze the body's metabolites. By detecting changes in metabolite types and quantities in different types of samples, it can sensitively discover the physiological and pathological changes in the body. It has great potential for clinical application and personalized medicine. It is promising and can help develop personalized treatment strategies based on the metabolic profiles of individuals. It can unravel the unique metabolic profiles of MB, which may revolutionize our understanding of the disease and improve patients' outcomes.PMID:39441459 | DOI:10.1007/s00432-024-05990-1

Funct Integr Genomics. 2024 Oct 23;24(6):194. doi: 10.1007/s10142-024-01481-1.ABSTRACTExtreme anthropogenic activities and current farming techniques exacerbate the effects of water and soil impurity by hazardous heavy metals (HMs), severely reducing agricultural output and threatening food safety. In the upcoming years, plants that undergo exposure to HM might cause a considerable decline in the development as well as production. Hence, plants have developed sophisticated defensive systems to evade or withstand the harmful consequences of HM. These mechanisms comprise the uptake as well as storage of HMs in organelles, their immobilization via chemical formation by organic chelates, and their removal using many ion channels, transporters, signaling networks, and TFs, amid other approaches. Among various cutting-edge methodologies, omics, most notably genomics, transcriptomics, proteomics, metabolomics, miRNAomics, phenomics, and epigenomics have become game-changing approaches, revealing information about the genes, proteins, critical metabolites as well as microRNAs that govern HM responses and resistance systems. With the help of integrated omics approaches, we will be able to fully understand the molecular processes behind plant defense, enabling the development of more effective crop protection techniques in the face of climate change. Therefore, this review comprehensively presented omics advancements that will allow resilient and sustainable crop plants to flourish in areas contaminated with HMs.PMID:39441418 | DOI:10.1007/s10142-024-01481-1

Arch Toxicol. 2024 Oct 23. doi: 10.1007/s00204-024-03876-2. Online ahead of print.ABSTRACTMulti-omics data integration has been repeatedly discussed as the way forward to more comprehensively cover the molecular responses of cells or organisms to chemical exposure in systems toxicology and regulatory risk assessment. In Canzler et al. (Arch Toxicol 94(2):371-388. https://doi.org/10.1007/s00204-020-02656-y ), we reviewed the state of the art in applying multi-omics approaches in toxicological research and chemical risk assessment. We developed best practices for the experimental design of multi-omics studies, omics data acquisition, and subsequent omics data integration. We found that multi-omics data sets for toxicological research questions were generally rare, with no data sets comprising more than two omics layers adhering to these best practices. Due to these limitations, we could not fully assess the benefits of different data integration approaches or quantitatively evaluate the contribution of various omics layers for toxicological research questions. Here, we report on a multi-omics study on thyroid toxicity that we conducted in compliance with these best practices. We induced direct and indirect thyroid toxicity through Propylthiouracil (PTU) and Phenytoin, respectively, in a 28-day plus 14-day recovery oral rat toxicity study. We collected clinical and histopathological data and six omics layers, including the long and short transcriptome, proteome, phosphoproteome, and metabolome from plasma, thyroid, and liver. We demonstrate that the multi-omics approach is superior to single-omics in detecting responses at the regulatory pathway level. We also show how combining omics data with clinical and histopathological parameters facilitates the interpretation of the data. Furthermore, we illustrate how multi-omics integration can hint at the involvement of non-coding RNAs in post-transcriptional regulation. Also, we show that multi-omics facilitates grouping, and we assess how much information individual and combinations of omics layers contribute to this approach.PMID:39441382 | DOI:10.1007/s00204-024-03876-2

Probiotics Antimicrob Proteins. 2024 Oct 23. doi: 10.1007/s12602-024-10379-0. Online ahead of print.ABSTRACTWe previously observed that supplementation with antimicrobial peptides facilitated the average daily weight gain, net meat, and carcass weights of Holstein bulls. To expand our knowledge of the possible impact of antimicrobial peptides on cecum microbiota, further investigations were conducted. In this study, 18 castrated Holstein bulls with insignificant weight differences and 10 months of age were split randomly into two groups. The control group (CK) was fed a basic diet, whereas the antimicrobial peptide group (AP) was supplemented with 8 g of antimicrobial peptides for 270 days. After slaughter, metagenomic and metabolomic sequencing analyses were performed on the cecum contents. The results showed significantly higher levels of amylase, cellulase, protease, and lipase in the CK than in the AP group (P ≤ 0.05). The levels of β-glucosidase and xylanase (P ≤ 0.05), and acetic and propionic acids (P ≤ 0.01), were considerably elevated in the AP than in the CK group. The metagenome showed variations between the two groups only at the bacterial level, and 3258 bacteria with differences were annotated. A total of 138 differential abundant genes (P < 0.05) were identified in the CAZyme map, with 65 genes more abundant in the cecum of the AP group and 48 genes more abundant in the cecum of the CK group. Metabolomic analysis identified 68 differentially expressed metabolites. Conjoint analysis of microorganisms and metabolites revealed that Lactobacillus had the greatest impact on metabolites in the AP group and Brumimicrobium in the CK group. The advantageous strains of the AP group Firmicutes bacterium CAG:110 exhibited a strong symbiotic relationship with urodeoxycholic acid and hyodeoxycholic acid. This study identified the classification characteristics, functions, metabolites, and interactions of cecal microbiota with metabolites that contribute to host growth performance. Antimicrobial peptides affect the cecal microorganisms, making the use of nutrients more efficient. The utilization of hemicellulose in the cecum of ruminants may contribute more than cellulose to their production performance.PMID:39441337 | DOI:10.1007/s12602-024-10379-0

ACS Chem Neurosci. 2024 Oct 23. doi: 10.1021/acschemneuro.4c00345. Online ahead of print.ABSTRACTThe occurrence and development of depression are closely related to disorders of the brain and peripheral substances. Abnormal metabolites in the blood affect the signal regulation function of the nerve center, which is one of the key factors for depression episodes. This study was focused on metabolites in serum and the mechanism of its antidepressant in the hippocampus. In the present study, serum metabolites in patients with depression were screened by metabolomic techniques. Various depressive mouse models and behavioral tests were used to assess its antidepressant effects. The expressions of inflammatory signaling were detected by using Western blot, ELISA, and immunofluorescence. We found that the metabolite hypoxanthine in the serum of patients with depression was significantly reduced, and the same result was also found in two mouse models of depression such as chronic unpredictable mild stress (CUMS) and social defeat stress (SD). By administering different doses of hypoxanthine (5, 10, 15 mg/kg), we found that only 15 mg/kg was able to significantly reduce the latency and increase food consumption in the novelty suppressed-feeding test (NSF), which was also able to reverse the depressive phenotypes of mice in the CUMS model after a single administration at 2 h later. Hypoxanthine obviously reduced the expressions of inflammation in serum and downregulated the expressions of MAPK and NLRP3-related pathways in the hippocampus in CUMS mice. Moreover, hypoxanthine also suppressed the activations of glial cells including GFAP and IBA-1 in hippocampal CA1, CA3, and dentate gyrus (DG). To sum up, hypoxanthine exerted antidepressant effect relying on the inhibition of peripheral and hippocampal inflammations by regulating MAPK, NLRP3-related pathways, and glial cells. This was the first time that we have found a disordered metabolite in patients with depression and further systematically demonstrated its efficacy and potential mechanism of antidepressants, providing new ideas for antidepressant drug development.PMID:39441118 | DOI:10.1021/acschemneuro.4c00345

J Agric Food Chem. 2024 Oct 23. doi: 10.1021/acs.jafc.4c04989. Online ahead of print.ABSTRACTStreptomyces species can form beneficial relationships with hosts as endophytes, including the phytopathogen-inhibiting strain, Streptomyces griseoaurantiacusMH191, isolated from wheat plants. Using genomic characterization and untargeted metabolomics, we explored the capacity of strain MH191 to inhibit a range of fungal phytopathogens through the production of secondary metabolites. Complete genome assembly of strain MH191 predicted 24 biosynthetic gene clusters. Secondary metabolite production was assessed following culture on six different media, with the detection of 205 putative compounds. Members of the manumycin family, undecylprodigiosin, and desferrioxamine were identified as the predominant metabolites. Antifungal activity was validated for undecylprodigiosin and manumycin. These compounds were produced from different BGCs, which showed similarity to asukamycin, undecylprodigiosin, and FW0622 gene clusters, respectively. The growth of strain MH191 on different media illustrated the metabolic regulation of these gene clusters and the strain's extended chemical potential, with the asukamycin gene cluster alone, producing a variety of antifungal metabolites. The study highlights the extended chemical capability of strain MH191, which could be exploited as a biological control agent for designing future crop protection solutions.PMID:39440812 | DOI:10.1021/acs.jafc.4c04989

J Clin Transl Hepatol. 2024 Oct 28;12(10):865-877. doi: 10.14218/JCTH.2024.00203. Epub 2024 Sep 19.ABSTRACTLiver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.PMID:39440217 | PMC:PMC11491507 | DOI:10.14218/JCTH.2024.00203

Front Immunol. 2024 Oct 8;15:1445769. doi: 10.3389/fimmu.2024.1445769. eCollection 2024.ABSTRACTINTRODUCTION: Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD).METHODS: Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils.RESULTS: Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes.DISCUSSION: ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.PMID:39439801 | PMC:PMC11493663 | DOI:10.3389/fimmu.2024.1445769

Br J Nutr. 2024 Oct 23:1-35. doi: 10.1017/S0007114524002526. Online ahead of print.ABSTRACTThe increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre "Western diets". Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinemia and insulin resistance in a murine model. Here we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2.5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance (HOMA-IR) compared to the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher faecal concentrations of several bile acids were detected in the treatment group when compared to the placebo after 8 weeks. These included tauroursodeoxycholic acid (TUDCA) which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in faecal microbiota composition or short-chain fatty acid (SCFA) levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.PMID:39439317 | DOI:10.1017/S0007114524002526

Alzheimers Dement. 2024 Oct 22. doi: 10.1002/alz.14249. Online ahead of print.ABSTRACTBACKGROUND: Metabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Although metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed.METHODS: We analyzed 342 postmortem brain samples from the Mayo Clinic Brain Bank and examined 658 metabolites in the cerebellar cortex and the temporal cortex between the two tauopathies.RESULTS: Our findings indicate that both diseases display oxidative stress associated with lipid metabolism, mitochondrial dysfunction linked to lysine metabolism, and an indication of tau-induced polyamine stress response. However, specific to AD, we detected glutathione-related neuroinflammation, deregulations of enzymes tied to purines, and cognitive deficits associated with vitamin B.DISCUSSION: Our findings underscore vast alterations in the brain's metabolome, illuminating shared neurodegenerative pathways and disease-specific traits in AD and PSP.HIGHLIGHTS: First high-throughput metabolic comparison of Alzheimer's diesease (AD) versus progressive supranuclear palsy (PSP) in brain tissue. Cerebellar cortex (CER) shows substantial AD-related metabolic changes, despite limited proteinopathy. AD impacts both CER and temporal cortex (TCX); PSP's changes are primarily in CER. AD and PSP share metabolic alterations despite major pathological differences.PMID:39439201 | DOI:10.1002/alz.14249

J Agric Food Chem. 2024 Oct 22. doi: 10.1021/acs.jafc.4c06793. Online ahead of print.ABSTRACTThis work was designed for the in-depth characterization and holistic comparison of up to 12 ginseng varieties, which can benefit the development of functional foods and ensure their authenticity in the food industry. An online comprehensive two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry (2D-LC/QTOF-MS) approach was established by configurating the XCharge C18 and HSS Cyano columns. Under the optimal conditions, we characterized a total of 1146 ginsenosides (including 876 potentially new compounds) from 12 ginseng varieties by reference to an in-house library of 573 known ginsenosides and 70 reference compounds. The online 2D-LC/QTOF-MS-based untargeted metabolomics workflows were developed, by which 126 potential ginsenoside markers were unveiled and utilized to establish the key identification points for each ginseng species. Compared with the conventional liquid chromatography/mass spectrometry metabolomics, our multidimensional chromatography approach performed better in discriminating multiple ginseng varieties. This work demonstrates a potent and practical methodology to identify easily confused functional plants.PMID:39439127 | DOI:10.1021/acs.jafc.4c06793

Environ Microbiome. 2024 Oct 22;19(1):78. doi: 10.1186/s40793-024-00624-y.ABSTRACTBACKGROUND: The symbiosis between arbuscular mycorrhizal fungi (AMF) and plants often stimulates plant growth, increases agricultural yield, reduces costs, thereby providing significant economic benefits. AMF can also benefit plants through affecting the rhizosphere microbial community, but the underlying mechanisms remain unclear. Using Rhizophagus intraradices as a model AMF species, we assessed how AMF influences the bacterial composition and functional diversity through 16 S rRNA gene sequencing and non-targeted metabolomics analysis in the rhizosphere of aluminum-sensitive soybean that were inoculated with pathogenic fungus Nigrospora oryzae and phosphorus-solubilizing fungus Talaromyces verruculosus in an acidic soil.RESULTS: The inoculation of R. intraradices, N. oryzae and T. verruculosus didn't have a significant influence on the levels of soil C, N, and P, or various plant characteristics such as seed weight, crude fat and protein content. However, their inoculation affected the structure, function and nutrient dynamics of the resident bacterial community. The co-inoculation of T. verruculosus and R. intraradices increased the relative abundance of Pseudomonas psychrotolerans, which was capable of N-fixing and was related to cry-for-help theory (plants signal for beneficial microbes when under stress), within the rhizosphere. R. intraradices increased the expression of metabolic pathways associated with the synthesis of unsaturated fatty acids, which was known to enhance plant resistance under adverse environmental conditions. The inoculation of N. oryzae stimulated the stress response inside the soil environment by enriching the polyene macrolide antifungal antibiotic-producing bacterial genus Streptomyces in the root endosphere and upregulating two antibacterial activity metabolic pathways associated with steroid biosynthesis pathways in the rhizosphere. Although inoculation of pathogenic fungus N. oryzae enriched Bradyrhizobium and increased soil urease activity, it had no significant effects on biomass and N content of soybean. Lastly, the host niches exhibited differences in the composition of the bacterial community, with most N-fixing bacteria accumulating in the endosphere and Rhizobium vallis only detected in the endosphere.CONCLUSIONS: Our findings demonstrate that intricate interactions between AMF, associated core fungi, and the soybean root-associated ecological niches co-mediate the regulation of soybean growth, the dynamics of rhizosphere soil nutrients, and the composition, function, and metabolisms of the root-associated microbiome in an acidic soil.PMID:39439005 | DOI:10.1186/s40793-024-00624-y

Arthritis Res Ther. 2024 Oct 22;26(1):181. doi: 10.1186/s13075-024-03414-6.ABSTRACTBACKGROUND: Abnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear.METHODS: Targeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber.RESULTS: We identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor.CONCLUSION: Our findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment.PMID:39438997 | DOI:10.1186/s13075-024-03414-6

BMC Genomics. 2024 Oct 22;25(1):989. doi: 10.1186/s12864-024-10877-z.ABSTRACTBACKGROUND: The tea plant Camellia sinensis (L.) O. Kuntze is a perennial crop, invaded by diversity of insect pest species, and pink tea mite is one of the most devastating pests for sustainable tea production. However, molecular mechanism of defense responses against pink tea mites in tea is still unknown. In this study, metabolomics and transcriptome profiles of susceptible and resistant tea varieties were compared before and after pink tea mite infestation.RESULTS: Metabolomics analysis revealed that abundance levels of polyphenol-related compounds changed significantly before and after infestation. At the transcript level, nearly 8 GB of clean reads were obtained from each sequenced library, and a comparison of infested plants of resistant and susceptible tea varieties revealed 9402 genes with significant differential expression. An array of genes enriched in plant pathogen interaction and biosynthetic pathways of phenylpropanoids showed significant differential regulation in response to pink tea mite invasion. In particular, the functional network linkage of disease resistant proteins, phenylalanine ammonia lyase, flavanone -3-hydroxylase, hydroxycinnamoyl-CoA shikimate transferase, brassinosteroid-6-oxidase 1, and gibberellin 2 beta-dioxygenase induced dynamic defense signals to suppress prolonged pink tea mite attacks. Further integrated analyses identified a complex network of transcripts and metabolites interlinked with precursors of various flavonoids that are likely modulate resistance against to pink tea mite.CONCLUSIONS: Our results characterized the profiles of insect induced metabolic and transcript reprogramming and identified a defense regulatory network that can potentially be used to fend off pink tea mites damage.PMID:39438821 | DOI:10.1186/s12864-024-10877-z

BMC Microbiol. 2024 Oct 22;24(1):421. doi: 10.1186/s12866-024-03583-z.ABSTRACTBACKGROUND: The addition of wine lees to diets can make up for the deficiencies caused by traditional forages in beef cattle farming. However, the effects of different wine lees ratios on average daily weight, gastrointestinal microbial community structure and metabolites in Guanling crossbred cattle have been rarely studied. This study assessed the effects of feeds containing wine lees on weight gain, gastrointestinal microbial community structure, and metabolites in Guanling crossbred cattle and elucidated the metabolic responses induced by wine lees. Eighteen cows were randomly assigned to receive fed concentrate (C group), feed containing 15% wine lees (group A), or feed containing 30% wine lees (group B) for 60 days.RESULTS: The average daily weight gain of group A and group B increased by 76.75% and 57.65%, respectively, compared with group C. Microbial community analysis showed that wine lees increased the abundance of Prevotella_1 in the rumen, decreased the abundance of Ruminococcaceae UCG 011 and Lachnospiraceae_FCS020_group in the rumen, and increased the abundance of Tyzzerella_4, Family_Xlll_AD3011_group, Granulicella, and Eisenbergiella in the cecum. Metabolomics analyses showed that wine lees decreased the concentrations of indole-3-ethanol in the rumen, and complexity cecal metabolism. Notably, linoleic acid metabolism was significantly enriched in both the rumen and cecum. Mantel test analyses indicated that the adverse effects of WL were reduced by stimulating the metabolism of linoleic acid, α-linolenic acid, and tryptophan, and these changes were mediated by intestinal microorganisms. The Guanling cattle cecum was enriched for several unfavorable metabolic pathways when wine lees concentrations reached 30%, which increased the likelihood of intestinal lesions.CONCLUSION: This study shows that WL supplementation alters gut microbiota and metabolic pathways, improving cattle growth and health. Moderate WL levels (15%) enhance gut health and beneficial pathways (e.g., linoleic and alpha-linolenic acid metabolism). However, higher WL inclusion (30%) may activate adverse pathways, raising the risk of intestinal damage. To maximize benefits and minimize risks, WL levels should be carefully managed.PMID:39438796 | DOI:10.1186/s12866-024-03583-z

Pediatr Res. 2024 Oct 22. doi: 10.1038/s41390-024-03669-4. Online ahead of print.ABSTRACTBACKGROUND: Anemia in preterm infants is associated with gut dysbiosis and necrotizing enterocolitis. Our study aimed to identify the bacterial functions and metabolites that can explain the underlying mechanisms of anemia associated disease conditions.METHODS: We conducted a case control study in preterm infants with cases having a hematocrit ≤ 25%. The control infants were matched by birth gestational age and weight. Fecal samples were collected before, at the onset, and after the onset of anemia in cases and with matched postnatal age in controls for metagenomics and metabolomics analyzes.RESULTS: 18 anemic and 20 control infants with fecal samples collected at 17 days, 5 weeks, and 7 weeks postnatal age were included. Virulence factor potential, decrease in beta diversity evolution, and larger changes in metabolome were associated with severe anemia. Metabolite abundances of N-acetylneuraminate and butyrobetaine were associated with virulence factor potential. Anemic group had decreased prostaglandin and lactic acid levels.CONCLUSION: Fecal omics data showed that severe anemia is associated with a pro-inflammatory gut microbiota with more virulent and less commensal anaerobic bacterial activities. Future studies can examine the link between anemia-associated dysbiosis and clinical outcomes and predict an infant-specific hematocrit threshold that negatively affects clinical outcomes.IMPACT: Severe anemia in preterm infants contributes to a pro-inflammatory gut with greater bacterial virulence and less commensal bacterial activities. The multiomics approach using non-invasive fecal biospecimens identified functional and metabolic changes in the gut microbiota and these mechanistic changes are plausible explanations for anemia-associated disease conditions in preterm infants. Our findings identified biological changes of the gut environment in severely anemic preterm infants that can offer guidance for clinical management.PMID:39438713 | DOI:10.1038/s41390-024-03669-4

Sci Rep. 2024 Oct 22;14(1):24810. doi: 10.1038/s41598-024-75556-1.ABSTRACTThe co-occurrence of multiple chronic conditions, termed multimorbidity, presents an expanding global health challenge, demanding effective diagnostics and treatment strategies. Chronic ailments such as obesity, diabetes, and cardiovascular diseases have been linked to metabolites interacting between the host and microbiota. In this study, we investigated the impact of co-existing conditions on risk estimations for 1375 plasma metabolites in 919 individuals from population-based Estonian Biobank cohort using liquid chromatography mass spectrometry (LC-MS) method. We leveraged annually linked national electronic health records (EHRs) data to delineate comorbidities in incident cases and controls for the 14 common chronic conditions. Among the 254 associations observed across 13 chronic conditions, we primarily identified disease-specific risk factors (92%, 217/235), with most predictors (93%, 219/235) found to be related to the gut microbiome upon cross-referencing recent literature data. Accounting for comorbidities led to a reduction of common metabolite predictors across various conditions. In conclusion, our study underscores the potential of utilizing biobank-linked retrospective and prospective EHRs for the disease-specific profiling of diverse multifactorial chronic conditions.PMID:39438584 | DOI:10.1038/s41598-024-75556-1

NPJ Biofilms Microbiomes. 2024 Oct 23;10(1):112. doi: 10.1038/s41522-024-00566-w.ABSTRACTBile acids (BAs) exert a profound influence on the body's pathophysiology by intricately shaping the composition of gut bacteria. However, the complex interplay between BAs and gut microbiota has impeded a systematic exploration of their impact on intestinal bacteria. Initially, we investigated the effects of 21 BAs on the growth of 65 gut bacterial strains in vitro. Subsequently, we examined the impact of BAs on the overall composition of intestinal bacteria, both in vivo and in vitro. The results unveiled distinct effects of various BAs on different intestinal strains and their diverse impacts on the composition of gut bacteria. Mechanistically, the inhibition of intestinal strains by BAs occurs through the accumulation of these acids within the strains. The intracellular accumulation of deoxycholic acid (DCA) significantly influenced the growth of intestinal bacteria by impacting ribosome transcription and amino-acid metabolism. The metabolomic analysis underscores the pronounced impact of DCA on amino-acid profiles in both in vivo and in vitro settings. This study not only elucidates the effects of BAs on a diverse range of bacterial strains and their role in shaping the gut microbiota but also reveals underlying mechanisms essential for understanding and maintaining a healthy gut microbiota.PMID:39438471 | DOI:10.1038/s41522-024-00566-w