PubMed

Cell Death Differ. 2024 Nov 16. doi: 10.1038/s41418-024-01410-6. Online ahead of print.ABSTRACTAcyl-CoA binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular checkpoint of autophagy. Here, we report that patients with histologically confirmed metabolic-associated steatohepatitis (MASH) or liver fibrosis exhibit elevated levels of circulating ACBP/DBI protein as compared to non-affected controls. Plasma ACBP/DBI strongly correlated with the NAFLD and FIB4 scores in patients, and these correlations were independent of age and body mass index. We studied the capacity of a monoclonal antibody (mAb) neutralizing mouse ACBP/DBI to combat active liver disease in several mouse models, in which steatohepatitis had been induced by four different protocols, namely, (i) methionine/choline-deficient diet, (ii) Western style diet (WD) alone, (iii) WD combined with the hepatotoxic agent CCl4, and (iv) a combination of CCl4 injections and oral ethanol challenge. Injections of anti-ACBP/DBI mAb attenuated histological, enzymological, metabolomic and transcriptomic signs of liver damage in these four models, hence halting or reducing the progression of non-alcoholic and alcoholic liver disease. Steatosis, inflammation, ballooning and fibrosis responded to ACBP/DBI inhibition at the preclinical level. Altogether, these findings support a causal role of ACBP/DBI in MASH and liver fibrosis, as well as the possibility to therapeutically target ACBP/DBI.PMID:39550516 | DOI:10.1038/s41418-024-01410-6

Sci Rep. 2024 Nov 16;14(1):28312. doi: 10.1038/s41598-024-79598-3.ABSTRACTThe remobilization of stored assimilates from stems to seeds plays a pivotal role in augmenting barley yield, particularly under water stress conditions. This study examines the molecular mechanisms underlying stem reserve utilization by conducting a comparative analysis of the proteome and metabolome across three barley contrasting genotypes: Yousef, Morocco, and PBYT17. Evaluations were performed at 21 and 28 days after anthesis (DAA) under both water stress and control conditions. The results indicate that the Yousef genotype exhibits superior remobilization of stem reserves, thereby demonstrating its potential to thrive even in adverse environmental conditions. Utilizing advanced quantitative proteomics and targeted metabolomics, this investigation identified a significant number of metabolites and proteins exhibiting differential accumulation across the genotypes. Specifically, 17 metabolites and 1580 proteins were catalogued, highlighting the intricate biochemical responses to water stress. Noteworthy enzymes such as sucrose synthase, inositol monophosphatase 3, and galactokinase were found to be closely associated with remobilization efficiency. In the drought-tolerant genotype, these enzymes maintained stable levels, in stark contrast to the decline observed in the susceptible genotype. This stability is crucial for promoting seed development through ascorbic acid synthesis and for mitigating oxidative stress, which is exacerbated by drought conditions. The elevated levels of certain metabolites, including glucose 6-phosphate, and UDP-glucose, in the drought-tolerant genotype suggest a robust mechanism for maintaining signalling molecules for carbon availability, which is then instrumental in regulating plant growth and seed size development. The findings from this study strongly imply that the drought-tolerant genotype, through enhanced antioxidant capacity, can effectively produce energy-rich storage compounds, thereby optimizing carbon allocation under water stress. Such insights are invaluable for future breeding strategies aimed at improving barley resilience in the face of climate variability.PMID:39550394 | DOI:10.1038/s41598-024-79598-3

Nat Commun. 2024 Nov 16;15(1):9947. doi: 10.1038/s41467-024-54181-6.ABSTRACTAberrant Ras homologous (Rho) GTPase signalling is a major driver of cancer metastasis, and GTPase-activating proteins (GAPs), the negative regulators of RhoGTPases, are considered promising targets for suppressing metastasis, yet drug discovery efforts have remained elusive. Here, we report the identification and characterization of adhibin, a synthetic allosteric inhibitor of RhoGAP class-IX myosins that abrogates ATPase and motor function, suppressing RhoGTPase-mediated modes of cancer cell metastasis. In human and murine adenocarcinoma and melanoma cell models, including three-dimensional spheroid cultures, we reveal anti-migratory and anti-adhesive properties of adhibin that originate from local disturbances in RhoA/ROCK-regulated signalling, affecting actin-dynamics and actomyosin-based cell-contractility. Adhibin blocks membrane protrusion formation, disturbs remodelling of cell-matrix adhesions, affects contractile ring formation, and disrupts epithelial junction stability; processes severely impairing single/collective cell migration and cytokinesis. Combined with the non-toxic, non-pathological signatures of adhibin validated in organoids, mouse and Drosophila models, this mechanism of action provides the basis for developing anti-metastatic cancer therapies.PMID:39550360 | DOI:10.1038/s41467-024-54181-6

Behav Brain Res. 2024 Nov 14:115339. doi: 10.1016/j.bbr.2024.115339. Online ahead of print.ABSTRACTBACKGROUND: Exercise is acknowledged for its beneficial effects on brain health; however, the intricate underlying molecular mechanisms remain poorly understood.AIMS: This study aimed to explore aerobic exercise-induced metabolic alterations in the brain.METHODS: We conducted an eight-week treadmill running exercise program in two-month-old male C57/BL6J mice. Body weight, serum lipid, glucose levels, and spatial cognition were measured. Spatial metabolomic analysis was performed to compare the metabolomic profiles across different brain regions. Immunohistochemical methods were used to compare the expression of carnitine palmitoyltransferase 1c (CPT1c).RESULTS: Exercise induced significant changes in the analysed metabolomic profiles. There were 904 differentially expressed metabolites (DEMs) detected in the whole brain section. Notable alterations in lipid profiles were observed, and among the 292 lipids detected, there were 74 (25.34%), 85 (29.11%), and 78 (26.71%) lipids differentially expressed in the hippocampus, thalamus, and hypothalamus of the Exe group, respectively. Lipid metabolism related pathways and enzymes were also altered, with L-carnitine and CPT1c upregulated in the three regions (p<0.05), and epinephrine levels decreased in the hippocampus (p<0.05). Furthermore, the vitamin B6 metabolism pathway was altered in the hypothalamus.CONCLUSIONS: This study highlighted the significant changes in lipid metabolism induced by involuntary exercise in the brains of young male mice. Exercise also altered epinephrine levels and the vitamin B12 metabolic pathway in specific brain regions, which indicated the multifaceted effects of exercise on the brain.PMID:39549874 | DOI:10.1016/j.bbr.2024.115339

Microbiol Res. 2024 Oct 28;290:127942. doi: 10.1016/j.micres.2024.127942. Online ahead of print.ABSTRACTMetabolites of plant and microbial origin have a great influence on plant-microbe interactions. Members from Bacillus subtilis are known to produce a plethora of metabolites that shape plant responses towards biotic and abiotic stresses. Similarly, endophyte B. subtilis L1-21 efficiently controls the Huanglongbing (HLB) causing pathogen: Candidatus Liberibacter asiaticus (CLas). However, the molecular mechanisms are highly elusive. Herein, our study highlights the critical role of endophyte L1-21 in planta-produced surfactin in its colonization in citrus plants and regulation of plant-microbe interactions by comparing three gene knockout mutants △srfAA-L1-21, △sfp-L1-21, and △pel-L1-21. All three mutants exhibited reduced pathogen control and colonization efficiency compared to wild-type (WT) L1-21, but knockout mutant deficient of surfactin △srfAA-L1-21 was significantly impaired in the abovementioned functions as compared to △sfp-L1-21 and △pel-L1-21. Further, △srfAA-L1-21 could not activate various metabolic pathways in citrus as WT-L1-21. Integrated metabolomic-transcriptomic analysis reveals that important secondary metabolites such as flavonoids, volatile organic compounds, and lignins were highly accumulated in citrus plants treated with WT-L1-21 as compared to △srfAA-L1-21, highlighting the role of surfactin as an elicitor of the defense system in citrus-HLB pathosystem. Interestingly, auxin-related metabolites and transcripts were also downregulated in △srfAA-L1-21 compared to WT-L1-21 showing that surfactin might also influence plant-microbe interactions through metabolic reprogramming. Further, higher enrichment of Bacilli with WT-L1-21 might corresponds to surfactin-mediated regulation of community-related behavior in Bacilli. To the best of our knowledge, this is the first study reporting the role of surfactin from Bacillus endophyte in metabolic reprogramming in citrus-HLB pathosystem and mounting defense response against CLas pathogen.PMID:39549644 | DOI:10.1016/j.micres.2024.127942

Ecotoxicol Environ Saf. 2024 Nov 15;288:117323. doi: 10.1016/j.ecoenv.2024.117323. Online ahead of print.ABSTRACTBenzo[a]pyrene (BaP), a major harmful component in PM2.5, is widely present in automobile emissions and atmospheric pollution. BaP exposure directly targets the lungs, often resulting in acute lung injury (ALI). However, comprehensive metabolic and transcriptomic profiles related to BaP-induced ALI remain unexplored. To simulate BaP-induced lung injury, we performed intratracheal instillation of BaP. To investigate how BaP exposure affects lung transcriptome and metabolic profiles, we used RNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). We aimed to understand the underlying mechanisms of BaP-induced lung damage. Metabolomics analyses indicated that in BaP-exposed animals, most fatty acids, carbohydrates, and steroids were significantly reduced, whereas most amino acids and organic acids remained unchanged. Analysis of transcriptomics data showed that fatty acid synthesis decreased and fatty acid oxidation increased, suggesting that lipid breakdown occurs after BaP exposure. Additionally, there were increases in oxidative stress system activity and decreases in immune system function. Finally, BaP altered mitochondrial, lipid, immune system, and fatty acid pathways, as indicated by pathway enrichment analyses. These results show that BaP substantially affects metabolic and inflammatory responses, enhancing the broader understanding of the underlying mechanisms of ALI after BaP exposure.PMID:39549570 | DOI:10.1016/j.ecoenv.2024.117323

Comput Biol Med. 2024 Nov 14;184:109393. doi: 10.1016/j.compbiomed.2024.109393. Online ahead of print.ABSTRACTSerum metabolome analysis is essential for identifying disease biomarkers and predicting patient outcomes in precision medicine. Thus, this study aims to compare Ultra-High Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS) with Fourier Transform Infrared (FTIR) spectroscopy in acquiring the serum metabolome of critically ill patients, associated with invasive mechanical ventilation (IMV), and predicting death. Three groups of 8 patients were considered. Group A did not require IMV and survived hospitalization, while Groups B and C required IMV. Group C patients died a median of 5 days after sample harvest. Good prediction models were achieved when comparing groups A to B and B to C using both platforms' data, with UHPLC-HRMS showing 8-17 % higher accuracies (≥83 %). However, developing predictive models using metabolite sets was not feasible when comparing unbalanced populations, i.e., Groups A and B combined to Group C. Alternatively, FTIR-spectroscopy enabled the development of a model with 83 % accuracy. Overall, UHPLC-HRMS data yields more robust prediction models when comparing homogenous populations, potentially enhancing understanding of metabolic mechanisms and improving patient therapy adjustments. FTIR-spectroscopy is more suitable for unbalanced populations. Its simplicity, speed, cost-effectiveness, and high-throughput operation make it ideal for large-scale studies and clinical translation in complex populations.PMID:39549530 | DOI:10.1016/j.compbiomed.2024.109393

Food Chem. 2024 Nov 12;465(Pt 1):141998. doi: 10.1016/j.foodchem.2024.141998. Online ahead of print.ABSTRACTDietary polysaccharides affect the intestinal microorganisms and their metabolites in the host. Clarifying the relationship among polysaccharides, intestinal microflora, and their metabolites is helpful to formulate dietary nutrition intervention strategies. Thus, we explored the regulatory effects of fucoidan on the human gut microbiota and its metabolites. After 48 h of fermentation, fucoidan significantly reduced the pH value in the broth, accompanied by an increase in total short-chain fatty acids, acetic acid, and propanoic acid contents. Fucoidan significantly reduced the relative abundance of Escherichia_shigella and Blebsiella and increased the relative abundance of Bifidobacterium and Lactobacillus. Concurrently, fucoidan altered the composition of intestinal microbial metabolites. These results indicate that fucoidan can regulate the metabolism of the intestinal flora and host, which may contribute to the intestinal health of the host.PMID:39549519 | DOI:10.1016/j.foodchem.2024.141998

Food Chem. 2024 Nov 9;465(Pt 1):141950. doi: 10.1016/j.foodchem.2024.141950. Online ahead of print.ABSTRACTProvence rosé wines have gained global popularity, making them vulnerable to fraud. This study aimed to identify specific chemical markers to detect counterfeit Provence rosé wines. An untargeted LC-MS-based metabolomics analysis was performed on a set of 30 wines classified as "Provence," "Non-Provence," and "Provence imitations." Using the Molnotator workflow, 1300 potential metabolites were generated, and five key chemomarkers were selected through a machine learning pipeline. Further targeted analysis and bioinformatics using in silico MS/MS fragmentation systems confidently annotated three specific chemomarkers for "Provence" rosé: acuminoside, tetrahydroxydimethoxyflavone, and 5'-methoxycastavinol. A composite score using a PLS model combining the 3 chemomarkers effectively distinguished authentic wines, with high accuracy (sensitivity 83.3 %, specificity 100 %, accuracy 93.3 %).PMID:39549510 | DOI:10.1016/j.foodchem.2024.141950

Tuberculosis (Edinb). 2024 Nov 13;149:102577. doi: 10.1016/j.tube.2024.102577. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary tuberculosis (PTB) is the main cause of infection-related mortality and the most common infectious disease that develops resistance to antibiotics. Gut microbiota and their associated metabolites are assumed to induce and influence the development of PTB. However, the alterations of gut microbiota and metabolites in TB patients is currently unclear.METHODS: Fecal samples were collected from 13 PTB patients, 13 LTBI patients, and 13 healthy controls (HC). 16S rRNA sequencing and metabolomics were used to analyze the changes in the intestinal microbiota and the composition of fecal metabolites in groups.RESULTS: Our findings indicated that the α-diversity of the gut microbiota in patients with PTB and LTBI decreases compared to HC, and at the phylum level, the relative abundance of Firmicutes decreases and the relative abundance of Bacteroides increases. And six genera were notably enriched in PTB patients and four in LTBI patients. Metabolomic analysis showed alterations in metabolite levels, such as short-chain fatty acids and amino acids.CONCLUSIONS: we comprehensively explored the changes in the gut microbes and fecal metabolites in patients with PTB and LTBI from the perspective of the gut microbiota, which may provide potential diagnostic biomarkers and therapeutic targets for TB diagnosis and treatment.PMID:39549509 | DOI:10.1016/j.tube.2024.102577

J Plant Physiol. 2024 Nov 9;303:154379. doi: 10.1016/j.jplph.2024.154379. Online ahead of print.ABSTRACTThe plant metabolome is considered an important interface between the genome and its phenome, where it plays a significant role in regulating plant growth in response to various environmental cues. A wide array of specialized metabolites is produced by plants, which are essential for mediating environmental interactions and their adaptation. Notably, enhanced accumulation of these specialized metabolites, particularly plant secondary metabolites (PSMs), is a part of the chemical defense response that is directly linked to improved stress tolerance. Therefore, exploring the genetic diversity underlying the immense variation of the secondary metabolite pool could unravel the adaptation mechanisms in plants against different environmental stresses. The post-genomic profiling platforms have enabled the exploration of the link between metabolic diversity and important agronomic traits. The current review focuses on the major achievements and future challenges associated with plant secondary metabolite (PSM) research in graminaceous crops using advanced omics approaches. Given this, we briefly summarize different strategies adopted to explore the genetic diversity and evolution of PSMs in cereal crops. Further, we have discussed the recent technological advancements to integrate multi-omics approaches linking the metabolome diversity with the genome, transcriptome, and proteome of these crops under stress. Combining these data with phenomics (the omics of phenotypes) provides a holistic view of how plants respond to stress. Next, we outlined the genetic manipulation studies performed so far in cereals to engineer secondary metabolic pathways for enhanced stress tolerance. In summary, our review provides new insight into developing genetic and genomic trends in exploring the secondary metabolite diversity in graminaceous crops and discusses how this information can be utilized in designing strategies to generate future stress-resilient crops.PMID:39549316 | DOI:10.1016/j.jplph.2024.154379

Sleep. 2024 Nov 16:zsae240. doi: 10.1093/sleep/zsae240. Online ahead of print.ABSTRACTSTUDY OBJECTIVES: To examine the joint effect of obstructive sleep apnea (OSA) and objective excessive daytime sleepiness (EDS) on glucose metabolism and the underlying mechanisms.METHODS: We included 127 patients with OSA. The multiple sleep latency test (MSLT) and Epworth sleepiness scale (ESS) were used to assess objective and subjective EDS, respectively. Disordered glucose metabolism was defined as either a physician diagnosis or having fasting blood glucose levels ≥ 5.6 mmol/L. Values of fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) higher than the median values of our sample were defined as high fasting insulin and insulin resistance. Serum metabolomics and fecal microbiota were used to explore underlying mechanisms.RESULTS: Lower MSLT values were associated with higher levels of fasting blood glucose, fasting insulin, and HOMA-IR. Furthermore, objective EDS was associated with increased odds of disordered glucose metabolism, elevated fasting insulin, and insulin resistance. Dysregulation of serum valine degradation and dysbiosis of fecal Bacteroides thetaiotaomicron were associated with impaired glucose metabolism in OSA with objective EDS. No association between subjective EDS and impaired glucose metabolism was observed.CONCLUSION: OSA with objective, but not subjective, EDS is associated with an increased risk of disordered glucose metabolism and insulin resistance. Dysregulation of valine degradation and dysbiosis of Bacteroides thetaiotaomicron appear to link objective EDS and disordered glucose metabolism in OSA.PMID:39549285 | DOI:10.1093/sleep/zsae240

STAR Protoc. 2024 Nov 15;5(4):103449. doi: 10.1016/j.xpro.2024.103449. Online ahead of print.ABSTRACTWe present a low-volume, direct analysis protocol for non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics, using 100 μL of urine. The steps include sample collection, stock solution preparation, metabolite extraction, two-step derivation with a drying phase, and analysis via two-dimensional GC time-of-flight MS (GCxGC-TOFMS). This protocol improves the efficiency and thoroughness of urinary metabolite analysis, contributing to advancements in metabolomics research, disease diagnosis, and biomarker discovery. For complete details on the use and execution of this protocol, please refer to Olivier et al.1.PMID:39549239 | DOI:10.1016/j.xpro.2024.103449

Metab Brain Dis. 2024 Nov 16;40(1):7. doi: 10.1007/s11011-024-01481-x.ABSTRACTThe biological basis for metabolic differences between unruptured and ruptured intracranial aneurysm (UIA and RIA) populations and their potential role in triggering IA rupture remain unclear. The aim of this study was to analyze the plasma metabolic profiles of patients with UIA and RIA using an untargeted metabolomic approach and to develop a model for early rupture classification. Plasma samples were analyzed using an ultra-high-performance liquid chromatography high-resolution tandem mass spectrometry-based platform. Least absolute shrinkage and selection operator regression and random forest machine learning methods were employed for metabolite feature selection and predictive model construction. Among 49 differential plasma metabolites identified, 31 were increased and 18 were decreased in the plasma of RIA patients. Five key metabolites-canrenone, piperine, 1-methyladenosine, betaine, and trigonelline-were identified as having strong potential to discriminate between UIA and RIA patients. This combination of metabolites demonstrated high diagnostic accuracy, with an area under the curve exceeding 0.95 in both the training and validation datasets. Our finding highlights the significance of plasma metabolites as potential biomarkers for early detection of IA rupture risk, offering new insights for clinical practice and future research on IA management.PMID:39549086 | DOI:10.1007/s11011-024-01481-x

J Diabetes Investig. 2024 Nov 16. doi: 10.1111/jdi.14355. Online ahead of print.ABSTRACTAIMS: This study aimed to identify metabolic markers for diabetic peripheral neuropathic pain (DPNP) in patients with type 2 diabetes mellitus (T2DM).MATERIALS AND METHODS: Blood metabolite levels in the amino acid, biogenic amine, sphingomyelin, phosphatidylcholine (PC), carnitines, and hexose classes were analyzed in nondiabetic control (n = 27), T2DM without DPNP (n = 58), and T2DM with DPNP (n = 29) using liquid chromatography tandem mass spectrometry. Variable importance projection (VIP) evaluation by partial least squares discriminant analysis was performed on clinical parameters and metabolites.RESULTS: Sixteen variables with VIP > 1.0 (P < 0.05) were identified across all patient groups, and 5 variables were identified to discriminate between the two T2DM groups. DPNP patients showed elevated fasting blood glucose, glutamate, PC aa C36:1, lysoPC a C18:1, and lysoPC a C18:2, while low-density lipoprotein cholesterol, phenylalanine, and tryptophan were reduced. Glutamate, lysoPC a C18:1, and lysoPC a C18:2 discriminated T2DM with DPNP from those without DPNP with an AUC of 0.671. The AUC was improved to 0.765 when ratios of metabolite pairs were considered.INTERPRETATION: Blood metabolites include glutamate, and phospholipid-related metabolites implicated in neuropathic pain may have the potential as biomarkers for DPNP. Further investigation is required to understand the mechanism of action of these altered metabolites in DPNP.PMID:39548809 | DOI:10.1111/jdi.14355

J Exp Bot. 2024 Nov 16:erae468. doi: 10.1093/jxb/erae468. Online ahead of print.ABSTRACTVirus infection brings about changes in the transcriptome, proteome and metabolome status of the infected plant wherein substantial alterations in the abundance of phytohormones and associated components involved in their signaling pathways have been observed. In the recent years, extensive research in the field of plant virology has showcased the undisputable significance of phytohormone signaling during plant-virus interactions. Apart from acting as growth regulators, phytohormones elicit robust immune response, which restricts the viral multiplication within the plant as well as its propagation by vector. Interestingly, these pathways have been shown to not only act as isolated mechanisms but as complex intertwined regulatory cascades where, the cross-talk among different phytohormones and with other antiviral pathways takes place during plant-virus interplay. Viruses cleverly disrupt phytohormone homeostasis via their multifunctional effectors that seems to be smart approach adopted by viruses to circumvent phytohormone-mediated plant immune responses. In this review, we summarize the current understanding of role of phytohormone signaling pathways during plant-virus interaction in activating antiviral immune responses of plant and also, how viruses exploit these signaling pathways favoring their pathogenesis.PMID:39548750 | DOI:10.1093/jxb/erae468

Microbiome. 2024 Nov 16;12(1):242. doi: 10.1186/s40168-024-01962-2.ABSTRACTBACKGROUND: Long-distance road transportation is a common practice in the beef industry, frequently resulting in bovine respiratory disease (BRD) and compromised growth performance. However, a comprehensive investigation integrating clinical performance, physiological conditions, and nasopharyngeal microflora remains lacking.METHODS: This study aimed to evaluate the respiratory health and immunometabolic status of 54 beef calves subjected to a 3000-km journey. The respiratory health of calves was monitored over 60 days post-arrival using a modified clinical scoring system. Nasopharyngeal microflora and venous blood samples were collected at 3 time points: before transportation (A), 30 days post-arrival (B), and 60 days post-arrival (C), for 16S rRNA microbiomics, whole-blood transcriptomics, serum metabolomics, and laboratory assays.RESULT: Within the first week post-arrival, the appetite and mental scores of calves dropped to zero, while other respiratory-related scores progressively declined over the 60 days. The α-diversity of nasopharyngeal microflora in calves was similar at time points A and B, both significantly higher than at time point C. The structure of these microbial communities varied significantly across different time points, with a notably higher relative abundance of BRD-related genera, such as Pasteurella and Mannheimia, detected at time point A compared to B and C. The composition and gene expression profiles of circulating blood cells at time point A were significantly different from those at B and C. Specifically, higher expression levels of oxidative- and inflammatory-related genes, cytokines, and enzymes were observed at time point A compared to B and C. Higher levels of catabolism-related metabolites and enzymes were detected at time point A, while higher levels of anabolism-related metabolites and enzymes were observed at time points B and C. Additionally, significant correlations were found among microorganisms, genes, and metabolites with differing abundances, expression levels, and concentrations across time points. Stronger correlations were observed between calves' performance and nasopharyngeal microflora and immunometabolic status at time point A compared to B or C.CONCLUSIONS: Collectively, these results confirm that 3000 km of road transportation significantly alters the composition and gene expression profiles of circulating white blood cells in calves, affects their metabolic processes, disrupts the balance of the respiratory microbial community, and leads to pronounced respiratory symptoms that persist for at least 60 days. During this period, the influenced composition and gene expression of circulating blood cells, metabolic processes, and nasopharyngeal microbial community gradually return to equilibrium, and the respiratory symptoms gradually diminish. This observational research indicates that transportation induces BRD in calves by disrupting the homeostasis of their immune function, metabolic processes, and nasopharyngeal microbial community. However, these results and their underlying molecular mechanisms warrant further validation through well-designed in vivo and in vitro confirmatory experiments with larger sample size. Video Abstract.PMID:39548602 | DOI:10.1186/s40168-024-01962-2

Microbiome. 2024 Nov 16;12(1):241. doi: 10.1186/s40168-024-01960-4.ABSTRACTBACKGROUND: Vestimentiferan tubeworms are deep-sea colonizers, in which chemoautotrophic symbiosis was first observed. These animals are gutless and depend on endosymbiotic bacteria for organic compound synthesis and nutrition supply. Taxonomically, vestimentiferans belong to Siboglinidae and Annelida. Compared with other siboglinids, vestimentiferans are distinguished by high tolerance of the prevailing hydrogen sulfide in hydrothermal vents, rapid growth in local habitats, and a physical structure consisting of a thick chitinous tube. The metabolic mechanisms contributing to these features remain elusive.RESULTS: Comparative genomics revealed that unlike other annelids, vestimentiferans possessed trehaloneogenesis and lacked gluconeogenesis. Transcriptome and metabolome analyses detected the expression of trehalose-6-phosphate synthase/phosphatase (TPSP), the key enzyme of trehaloneogenesis, and trehalose production in vestimentiferan tissues. In addition to trehaloneogenesis, glycogen biosynthesis evidenced by packed glycogen granules was also found in vestimentiferan symbionts, but not in other Siboglinidae symbionts. Data mining and analyses of invertebrate TPSP revealed that the TPSP in Vestimentifera, as well as Cnidaria, Rotifera, Urochordata, and Cephalochordata, likely originated from Arthropoda, possibly as a result of transposon-mediated inter-phyla gene transfer.CONCLUSION: This study indicates a critical role of bacterial glycogen biosynthesis in the highly efficient symbiont - vestimentiferan cooperation. This study provides a new perspective for understanding the environmental adaptation strategies of vestimentiferans and adds new insights into the mechanism of metabolic evolution in Metazoa. Video Abstract.PMID:39548600 | DOI:10.1186/s40168-024-01960-4

Gut Pathog. 2024 Nov 15;16(1):69. doi: 10.1186/s13099-024-00662-4.ABSTRACTBACKGROUND: Cow milk, which is sometimes consumed raw, hosts a plethora of microorganisms, some of which are beneficial, while others raise food safety concerns. In this study, the draft genome of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae subsp. pneumoniae strain Cow102, isolated from raw cow milk used to produce traditional foods in Nigeria, is reported.RESULT: The genome has a total length of 5,359,907 bp, with 70 contigs and a GC content of 57.35%. A total of 5,244 protein coding sequences were detected with 31% mapped to a subsystem, and genes coding for amino acids and derivatives being the most prevalent. Multilocus sequence typing revealed that the strain had new allelic profile assigned to the novel 6914 sequence type possessing capsular and lipopolysaccharide antigen K locus 122 with an unknown K type (KL122) and O locus O1/O2v2 with type O2afg, respectively. A total of 28 resistance-related genes, 98 virulence-related genes, two plasmids and five phages were identified in the genome. The resistance genes oqxA, oqxB and an IS3 belonging to cluster 204 were traced to bacteriophage Escher 500,465. Comparative analysis predicted one strain specific orthologous group comprising three genes.CONCLUSION: This report of a novel sequence type (ST6914) in K. pneumoniae presents a new allelic profile, indicating ongoing evolution and diversification within the species. Its uniqueness suggests it may represent a locally evolved lineage, although further sampling would be necessary to confirm this hypothesis. The strain's multidrug resistance, virulence gene repertoire, and isolation from animal milk render it a potentially significant public health concern, underscoring the importance of genomic surveillance in non-clinical settings to detect emerging strains. Further research is required to fully characterise the capsular K type of ST6914.PMID:39548558 | DOI:10.1186/s13099-024-00662-4

J Transl Med. 2024 Nov 15;22(1):1028. doi: 10.1186/s12967-024-05786-4.ABSTRACTPURPOSE: Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice.METHODS: The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.RESULT: Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide.CONCLUSION: The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.PMID:39548468 | DOI:10.1186/s12967-024-05786-4