PubMed

Food Funct. 2024 Nov 27. doi: 10.1039/d4fo01878h. Online ahead of print.ABSTRACTEmerging evidence suggests that Parkinson's disease (PD) is strongly associated with altered gut microbiota. The present study investigated the prophylactic effects of anthocyanins (ACNs) from Lycium ruthenicum Murray on Parkinson's disease based on microbiomics and metabolomics. In this study, sixty-six adult male C57BL/6J mice were randomized into the control group, model group, positive drug (Madopar) group, and low-, medium- and high-dose ACN groups. Behavioral experiments were conducted and pathological indicators were determined. Fresh feces were collected for microbiomic analysis using 16S rRNA sequencing. Urine and serum were analyzed by the UPLC-MS method for untargeted metabolomics. The results demonstrated that ACNs ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits, dopamine neuron death, and glial cell activation, while 100 mg kg-1 and 200 mg kg-1 ACNs were more neuroprotective than 50 mg kg-1. Mice with PD-like phenotypes have an altered gut microbiota composition, and ACNs may regulate this disorder by causing an increase in Firmicutes/Bacteroidota ratio and abundance of norank_f__Eubacterium_coprostanoligenes_group and a decrease in the abundance of norank_f__Muribaculaceae, Coriobacteriaceae_UCG-002 and Parvibacter. Furthermore, ACNs increased 14 urinary key metabolites such as DIMBOA-Glc and tauroursodeoxycholic acid, decreased N,N-dimethyllysine, and increased 12 serum key metabolites such as 1-methylguanine and 1-nitro-5-glutathionyl-6-hydroxy-5,6-dihydronaphthalene, and decreased lamivudine-monophosphate and 5-butyl-2- methylpyridine. The present study reveals that ACNs are protective against MPTP-induced PD in mice by modulating anti-inflammatory flora in the gut and endogenous metabolites in serum/urine, and the key mechanisms may be related to Coriobacteriaceae_UCG-002 and glycerophospholipid metabolic pathways. Our findings provide new insights into the pathogenesis and potential treatment of Parkinson's disease.PMID:39601125 | DOI:10.1039/d4fo01878h

Front Endocrinol (Lausanne). 2024 Nov 12;15:1443330. doi: 10.3389/fendo.2024.1443330. eCollection 2024.ABSTRACTBACKGROUND: Recently, serum metabolites have shown potential in predicting survival outcomes and may be related to the pathogenesis of prostate cancer. Nevertheless, the precise impact concerning the genetic effect of metabolites on prostate cancer risk remains obscure. In this context, we conducted a Mendelian randomization (MR) study aiming to explore the causality between genetically determined metabolites and the risk of prostate cancer.METHODS: We conducted a two-sample MR analysis aiming to identify the underlying metabolites associated with prostate cancer. Exposure information was obtained from the largest metabolome-based genome-wide association (GWAS) data containing 7,824 Europeans. Genome-wide association analysis was utilized to detect instrumental variables (IVs) for metabolites. We applied the inverse-variance weighted (IVW) approach as the primary method, and to augment the reliability and robustness of our findings, additional analysis methods encompassing weighted median, MR-Egger, and leave-one-out analysis were utilized. MR-Egger intercept test was implemented to explore the pleiotropy. Cochran's Q test was utilized to quantify the degree of heterogeneity. Additionally, we performed metabolic pathway analysis and single-cell RNA sequencing analysis.RESULTS: We found that three serum metabolites were causally associated with prostate cancer after utilizing rigorous screening standards. Utilizing single nucleotide polymorphisms as IVs, a 1-SD increase in fructose was associated with 77% higher risk of prostate cancer (OR:1.77, 95%CI: 1.05-2.97, PIVW=0.031), a 1-SD increase in N1-methyl-3-pyridone-4-carboxamide was associated with 29% higher risk of prostate cancer (OR:1.29, 95%CI: 1.05-1.58, PIVW=0.017), and a 1-SD increase in 12-hydroxyeicosatetraenoate (12-HETE) was associated with 18% higher risk of prostate cancer (OR:1.18, 95%CI: 1.07-1.31, PIVW=0.0008). Metabolites that were causally linked to the risk of prostate cancer were mainly enriched in the valine, leucine and isoleucine biosynthesis pathway (P=0.026) and the nicotinate and nicotinamide metabolism pathway (P=0.048).CONCLUSIONS: Our MR analysis provided suggestive evidence supporting the causal relationships between three identified serum metabolites and prostate cancer, necessitating further investigation to elucidate the underlying mechanisms through which these blood metabolites and metabolic pathways may impact the initiation and progression of prostate cancer.PMID:39600951 | PMC:PMC11590024 | DOI:10.3389/fendo.2024.1443330

Front Endocrinol (Lausanne). 2024 Nov 12;15:1409079. doi: 10.3389/fendo.2024.1409079. eCollection 2024.ABSTRACTBACKGROUND: The pathological and physiological characteristics between HBsAg-positive HBV infection and occult hepatitis B infection (OBI) are currently unclear. This study aimed to explore the immune microenvironment in the peripheral circulation of OBI patients through integration of proteomic and metabolomic sequencing, and to identify molecular biomarkers for clinical diagnosis of HBsAg-positive HBV and OBI.METHODS: This research involved collection of plasma from 20 patients with OBI (negative for HBsAg but positive for HBV DNA, with HBV DNA levels < 200 IU/mL), 20 patients with HBsAg-positive HBV infection, and 10 healthy individuals. Mass spectrometry-based detection was used to analyze the proteome, while nuclear magnetic resonance spectroscopy was employed to study the metabolomic phenotypes. Differential molecule analysis, pathway enrichment and functional annotation, as well as weighted correlation network analysis (WGCNA), were conducted to uncover the characteristics of HBV-related liver disease. Prognostic biomarkers were identified using machine learning algorithms, and their validity was confirmed in a larger cohort using enzyme linked immunosorbent assay (ELISA).RESULTS: HBsAg-positive HBV individuals showed higher ALT levels (p=0.010) when compared to OBI patients. The influence of HBV infection on metabolic functions and inflammation was evident through the analysis of distinct metabolic pathways in HBsAg-positive HBV and OBI groups. Tissue tracing demonstrated a connection between Kupffer cells and HBsAg-positive HBV infection, as well as between hepatocytes and OBI. Immune profiling revealed the correlation between CD4 Tem cells, memory B cells and OBI, enabling a rapid response to infection reactivation through cytokine secretion and antibody production. A machine learning-constructed and significantly expressed molecule-based diagnostic model effectively differentiated HBsAg-positive and OBI groups (AUC values > 0.8). ELISA assay confirmed the elevation of FGB and FGG in OBI samples, suggesting their potential as biomarkers for distinguishing OBI from HBsAg-positive infection.CONCLUSIONS: The immune microenvironment and metabolic status of HBsAg-positive HBV patients and OBI patients vary significantly. The machine learning-based diagnostic model described herein displayed impressive classification accuracy, presenting a non-invasive means of differentiating between OBI and HBsAg-positive HBV infections.PMID:39600945 | PMC:PMC11588476 | DOI:10.3389/fendo.2024.1409079

Front Plant Sci. 2024 Nov 12;15:1461442. doi: 10.3389/fpls.2024.1461442. eCollection 2024.ABSTRACTCamellia japonica 'High Fragrance' is a camellia hybrid known for its unique and intense floral scent. The current understanding of the dynamic changes in its fragrance and the underlying mechanisms are still limited. This study employed a combination of metabolomic and transcriptomic approaches to reveal the characteristics of the metabolites involved in the remarkable fragrance of this camellia and their biosynthetic mechanisms along three flower developmental stages (flower bud, initial bloom, and full bloom). Among the 349 detected volatile organic compounds (VOCs), the majority were terpenes (57, 16.33%) and esters (53, 15.19%). Of these, 136 VOCs exhibited differential accumulation over time. Transcriptomic data from floral organs at different flowering stages identified 56,303 genes, with 13,793 showing significant differential expression. KEGG enrichment analysis revealed 57, 91, and 33 candidate differential genes related to the biosynthesis of terpenes, phenylpropanoids, and fatty acid derivatives, respectively. This indicates that terpenes, esters, and their related synthetic genes might play a crucial role in the formation of 'High Fragrance' characteristics. During the entire flowering process, the majority of genes exhibited an elevated expression pattern, which correlated with the progressive accumulation of VOCs. Interestingly, the expression patterns of the differentially expressed genes in the mevalonate (MVA) and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathways, associated with terpene synthesis, showed opposite trends. A transcriptional-metabolic regulatory network linking terpenoid compounds, related synthetic enzymes, and potential transcription factors could be outlined for 'High Fragrance' camellia, thus providing a theoretical basis for further exploring these events and breeding more fragrant camellias.PMID:39600898 | PMC:PMC11588446 | DOI:10.3389/fpls.2024.1461442

J Inflamm Res. 2024 Nov 22;17:9407-9422. doi: 10.2147/JIR.S488638. eCollection 2024.ABSTRACTOBJECTIVE: This study aimed to investigate the role of immune inflammation in recurrent spontaneous abortions (RSA).METHODS: In this study, decidua tissues from 12 patients were collected. These included six individuals with RSA in the RSA group and six in the control group. The differences in gene and metabolite expression in the decidua of the placenta between normal pregnancies and patients with RSA were compared using transcriptomic and metabolomic analyses. The differentially expressed genes and metabolites were further analyzed through functional enrichment analysis using high-throughput sequencing technology.RESULTS: There was a significant upregulation of genes associated with immunity and inflammation in the RSA group compared to the control group. The TNF signaling pathway was upregulated in the RSA group. Inflammatory mediators were expressed at higher levels in the RSA group, and arachidonic acid metabolism was the most significant differential metabolite set. The regulation of inflammatory mediators of transient receptor potential (TRP) channels were enriched in RSA cases. The integrated analysis of the data further suggests that the immune-inflammatory response might be an important factor in RSA. The expression levels of genes related to inflammation and hypoxia in tissues from patients with RSA were verified using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and this revealed that the expression of MARK10 and TNFAIP3 genes was significantly upregulated in samples from RSA patients compared to normal tissues.CONCLUSION: The findings suggest a strong association between immune-related inflammation and RSA. Addressing metabolic and inflammatory aspects in patients with RSA may potentially help enhance pregnancy outcomes.PMID:39600677 | PMC:PMC11590633 | DOI:10.2147/JIR.S488638

Ther Adv Musculoskelet Dis. 2024 Nov 25;16:1759720X241299535. doi: 10.1177/1759720X241299535. eCollection 2024.ABSTRACTBACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease that poses a significant global healthcare challenge due to its complexity and limited treatment options. Advances in metabolomics have provided insights into OA by identifying dysregulated metabolites and their connection to altered signaling pathways. However, a comprehensive understanding of these biomarkers in OA is still required.OBJECTIVES: This systematic review aims to identify metabolomics biomarkers associated with dysregulated signaling pathways in OA, using data from various biological samples, including in vitro models, animal studies, and human research.DESIGN: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.DATA SOURCES AND METHODS: Data were gathered from literature published between August 2017 and May 2024, using databases such as "PubMed," "Scopus," "Web of Science," and "Google Scholar." Studies were selected based on keywords like "metabolomics," "osteoarthritis," "amino acids," "molecular markers," "biomarkers," "diagnostic markers," "inflammatory cytokines," "molecular signaling," and "signal transduction." The review focused on identifying key metabolites and their roles in OA-related pathways. Limitations include the potential exclusion of studies due to keyword selection and strict inclusion criteria.RESULTS: The meta-analysis identified dysregulated metabolites and associated pathways, highlighting a distinct set of related metabolites consistently altered across the studies analyzed. The dysregulated metabolites, including amino acids, lipids, and carbohydrates, were found to play critical roles in inflammation, oxidative stress, and energy metabolism in OA. Metabolites such as alanine, lysine, and proline were frequently linked to pathways involved in inflammation, cartilage degradation, and apoptosis. Key pathways, including nuclear factor kappa B, mitogen-activated protein kinase, Wnt/β-catenin, and mammalian target of rapamycin, were associated with changes in metabolite levels, particularly in proinflammatory lipids and energy-related compounds.CONCLUSION: This review reveals a complex interplay between dysregulated metabolites and signaling pathways in OA, offering potential biomarkers and therapeutic targets. Further research is needed to explore the molecular mechanisms driving these changes and their implications for OA treatment.PMID:39600593 | PMC:PMC11590150 | DOI:10.1177/1759720X241299535

Research (Wash D C). 2024 Nov 26;7:0539. doi: 10.34133/research.0539. eCollection 2024.ABSTRACTBackground: Clear cell renal cell carcinoma (ccRCC) is a prevalent malignant tumor of the urinary system. While tyrosine kinase inhibitors (TKIs) are currently the first-line treatments for advanced/metastatic ccRCC, patients often develop resistance after TKI therapy. Lipid metabolic reprogramming, a hallmark of tumor progression, contributes to acquired drug resistance in various malignant tumors. Mitophagy, a process that maintains mitochondrial homeostasis, aids tumor cells in adapting to microenvironmental changes and consequently developing drug resistance. Solute carrier family 27 member 3 (SLC27A3), highly expressed in lipid-rich tumors like ccRCC, has been associated with poor prognosis. However, the impact of SLC27A3 and the transcription factor complex containing STAT2 on lipid metabolic reprogramming, mitophagy in ccRCC, and their role in TKI resistance remain unexplored. Methods: 786-O to pazopanib resistance was induced by gradient increase of concentration, and the genes related to lipid metabolism were screened by RNA sequencing. Bioinformatics was used to analyze the differential expression of SLC27A3 and its effect on patient prognosis, and to predict the activated pathway in pazopanib-resistant cells. Lipid droplets (LDs) were detected by Red Oil O and BODIPY probe. Micro-targeted lipidomic of acyl-coenzyme A (CoA) and lipid metabolomics were performed to screen potential metabolites of SLC27A3. The differential expression of SLC27A3 was detected in clinical samples. The differential expression of SLC27A3 and its effect on drug resistance of ccRCC tumor were detected in vitro and in vivo. Mitophagy was detected by electron microscopy, Mtphagy probe, and Western blot. The mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were detected by JC-1 and DCF probes. The binding site of the transcription factor complex to the SLC27A3 promoter was detected by dual-luciferase reporter gene assay. Results: SLC27A3, highly expressed in lipid-rich tumors such as ccRCC and glioblastoma, predicts poor prognosis. SLC27A3 expression level also increased in pazopanib-resistant 786-O cells (786-O-PR) with more LD accumulation compared to parental cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis from RNA sequencing showed that PINK1/Parkin-mediated mitophagy pathway was enriched in 786-O-PR. Knockdown of SLC27A3 markedly suppressed LD accumulation and mitophagy, and overcame pazopanib resistance in vitro and in vivo. Moreover, SLC27A3 functions as an acyl-CoA ligase catalyzing the formation of acyl-CoA, which refers to fatty acid oxidation accompanied by ROS production and synthesis of lipid. Overproduced acyl-CoA oxidation in mitochondria resulted in MMP decrease and amounts of ROS production, subsequently triggering PINK1/Parkin-mediated mitophagy. Moreover, mitophagy inhibition led to more ROS accumulation and cell death, indicating that mitophagy can keep ROS at an appropriate level by negative feedback. Mitophagy, simultaneously, prevented fatty acid oxidation in mitochondria by consuming CPT1A, forcing synthesis of triglycerides and cholesterol esters stored in LDs by transforming acyl-CoA, to support ccRCC progression. Besides, we found that STAT2 expression was positively correlated to SLC27A3. Transcriptional factor complex containing STAT2 could bind to the promoter of SLC27A3 mRNA to promote SLC27A3 transcription proved by dual-luciferase reporter assay, which also regulated LD metabolism and activated mitophagy during pazopanib resistance. Conclusion: SLC27A3 is up-regulated in pazopanib-resistant ccRCC and predicts poor prognosis. High expression of SLC27A3 produces excessive metabolites of various long-chain fatty acyl-CoA (12:0-, 16:0-, 17:0-, 20:3-CoA) to enter mitochondria for β-oxidation and produce amounts of ROS activating mitophagy. Subsequent mitophagy/ROS negative feedback controls ROS homeostasis and consumes CPT1A protein within mitochondria to suppress fatty acid β-oxidation, forcing acyl-CoA storage in LDs, mediating pazopanib resistance in ccRCC. Furthermore, STAT2 was identified as a core component of a potential upstream transcriptional factor complex for SLC27A3. Our findings shed new light on the underlying mechanism of SLC27A3 in ccRCC TKI resistance, which may provide a novel therapeutic target for the management of ccRCC.PMID:39600540 | PMC:PMC11588985 | DOI:10.34133/research.0539

Front Genet. 2024 Nov 12;15:1450064. doi: 10.3389/fgene.2024.1450064. eCollection 2024.ABSTRACTBACKGROUND: Aging can impair the ability of elderly individuals to fight infections and trigger persistent systemic inflammation, a condition known as inflammaging. However, the mechanisms underlying the development of inflammaging remain unknown.METHODS: We conducted 16S rRNA sequencing of intestinal contents from young and old C57BL/6J mice to elucidate changes in gut microbiota diversity and microbial community composition after aging. Aging-related differential bacterial taxa were then identified, and their abundance trends were validated in human samples. The variances in intestinal barrier function and circulating endotoxin between groups were also assessed. Furthermore, widely targeted metabolomics was conducted to characterize metabolic profiles after aging and to investigate the key metabolic pathways enriched by the differential metabolites.RESULTS: Our findings demonstrated an increase in relative proportion of pathogenic bacteria with age, a trend also revealed in healthy populations of different age groups. Additionally, aging individuals exhibited reduced intestinal barrier function and increased circulating endotoxin levels. Widely targeted metabolomics revealed a significant increase in various secondary bile acid metabolites after aging, positively correlated with the relative abundance of several aging-related bacterial taxa. Furthermore, old group had lower levels of various anti-inflammatory or beneficial metabolites. Enrichment analysis identified the starch and sucrose metabolism pathway as potentially the most significantly impacted signaling pathway during aging.CONCLUSION: This study aimed to provide insights into the complex interactions involved in organismal inflammaging through microbial multi-omics. These findings lay a solid foundation for future research aimed at identifying novel biomarkers for the clinical diagnosis of aging-related diseases or potential therapeutic targets.PMID:39600316 | PMC:PMC11588687 | DOI:10.3389/fgene.2024.1450064

Viruses. 2024 Nov 13;16(11):1769. doi: 10.3390/v16111769.ABSTRACTCOVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a 1H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH3)3 choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.PMID:39599883 | DOI:10.3390/v16111769

Nutrients. 2024 Nov 20;16(22):3970. doi: 10.3390/nu16223970.ABSTRACTBACKGROUND: The novel coronavirus (SARS-CoV-2) led to gastrointestinal manifestations in up to 50% of cases, with diarrhea being common, and probiotics have been suggested as a potential treatment.AIM: This study aimed to assess changes in the microbiome and the effects of a multispecies probiotic in patients with COVID-19 in home quarantine through a fully remote telemedical approach.METHODS: Thirty patients were randomized to receive either the Ecologic AAD probiotic (Winclove Probiotics, Amsterdam, The Netherlands), on the market as OMNi-BiOTiC 10 (Allergosan, Austria), or a placebo for 30 days in a 2:1 ratio. Respiratory and gastrointestinal symptoms were monitored in 2-10-day intervals via online surveys, and five stool samples were collected during the 30-day study period for microbiome and metabolomics analyses. Twenty-four healthy volunteers served as controls.RESULTS: Of the 30 patients, 26 completed this study (10 placebo, 16 probiotic). Patients reported respiratory symptoms and a diminished gastrointestinal quality of life, both of which improved significantly during the study period, irrespective of the intervention. Compared to controls, infected patients showed significant alterations in the fecal microbiome (p = 0.002), including an increase in Bacteroidetes and decreases in Christensenellaceae, Ruminococcaceae, and Gammaproteobacteria, along with metabolomic changes. Probiotic treatment significantly modulated the patients' microbiome beta diversity (p = 0.001) and introduced the Enterococcus faecium W54 strain. Symptoms, COVID-19-related taxa, and the fecal metabolome were not affected by the intervention.CONCLUSIONS: Patients with mild COVID-19 disease in home quarantine exhibited respiratory symptoms, a reduced gastrointestinal quality of life, and changes in the fecal microbiome and metabolome.PMID:39599756 | DOI:10.3390/nu16223970

Nutrients. 2024 Nov 19;16(22):3943. doi: 10.3390/nu16223943.ABSTRACTBACKGROUND: Endurance athletes require tailored nutrition strategies to optimize performance, recovery, and training adaptations. While traditional sports nutrition guidelines provide a foundational framework, individual variability in metabolic responses underscores the need for precision nutrition, informed by genetic, biological, and environmental factors. This scoping review evaluates the application of systems biology-driven sports nutrition for endurance athletes, focusing on 'omics' and wearable technologies.METHODS: A scoping review of the literature was conducted in PubMed, Scopus, and Web of Science in accordance with the PRISMA-ScR checklist. Research questions, search strategies, and eligibility criteria were guided by the Population-Concept-Context framework with the following inclusion criteria: original research in English, involving endurance athletes, systems biology approaches, and nutritional interventions or continuous glucose monitoring (CGM).RESULTS: Fifty-two studies were included, with distance runners as the most studied cohort. Eleven studies used metagenomics, eleven CGM, ten nutrigenetics, ten metabolomics, seven multi-omics, one proteomics, one epigenomics, and one lipidomics. Over half (n = 31; 60%) were randomized controlled trials (RCTs) with generally high methodological quality.CONCLUSIONS: Most studies were proof-of-concept investigations aimed at assessing biomarkers; however, the evidence linking these biomarkers to performance, recovery, and long-term health outcomes in endurance athletes remains insufficient. Future research should focus on well-powered replicated crossover RCTs, multivariate N-of-1 clinical trials, 360-degree systems-wide approaches, and the validation of genetic impacts on nutritional interventions to refine dietary guidelines.PMID:39599728 | DOI:10.3390/nu16223943

Nutrients. 2024 Nov 17;16(22):3921. doi: 10.3390/nu16223921.ABSTRACTHuman milk (HM) is a complex biofluid rich in nutrients and bioactive compounds essential for infant health. Recent advances in omics technologies-such as proteomics, metabolomics, and transcriptomics-have shed light on the influence of HM on bone development and health. This review discusses the impact of various HM components, including proteins, lipids, carbohydrates, and hormones, on bone metabolism and skeletal growth. Proteins like casein and whey promote calcium absorption and osteoblast differentiation, supporting bone mineralization. Long-chain polyunsaturated fatty acids like docosahexaenoic acid (DHA) contribute to bone health by modulating inflammatory pathways and regulating osteoclast activity. Additionally, human milk oligosaccharides (HMOs) act as prebiotics, improving gut health and calcium bioavailability while influencing bone mineralization. Hormones present in HM, such as insulin-like growth factor 1 (IGF-1), leptin, and adiponectin, have been linked to infant growth, body composition, and bone density. Research has shown that higher IGF-1 levels in breast milk are associated with increased weight gain, while leptin and adiponectin influence fat mass and bone metabolism. Emerging studies have also highlighted the role of microRNAs (miRNAs) in regulating key processes like adipogenesis and bone homeostasis. Furthermore, microbiome-focused techniques reveal HM's role in establishing a balanced infant gut microbiota, indirectly influencing bone development by enhancing nutrient absorption. Although current findings are promising, comprehensive longitudinal studies integrating omics approaches are needed to fully understand the intricate relationships among maternal diet, HM composition, and infant bone health. Bridging these gaps could offer novel dietary strategies to optimize skeletal health during infancy, advancing early-life nutrition science.PMID:39599707 | DOI:10.3390/nu16223921

Nutrients. 2024 Nov 11;16(22):3851. doi: 10.3390/nu16223851.ABSTRACTBACKGROUND: Cardiovascular disease (CVD) is the predominant cause of mortality, with aging being a significant risk factor. Nucleotides (NTs), essential for numerous biological functions, are particularly vital under conditions like aging, starvation, and nutrient deficiency. Although the antiaging benefits of exogenous NTs have been recognized in various systems, their cardiac-specific effects are not well understood. This study, therefore, investigated the impact of exogenous NTs on cardiac aging and delved into the potential mechanisms.METHODS: Senescence-accelerated mouse prone-8 (SAMP8) mice were utilized, randomly assigned to one of three groups: a control group (Control), a low-dose NTs group (NTs_L), and a high-dose NTs group (NTs_H). Meanwhile, senescence-accelerated mouse resistant 1 (SAMR1) mice were set up as the SAMR1 group. Following a 9-month intervention, cardiac tissues were subjected to analysis.RESULTS: The results showed that NTs improved the morphological structure of the cardiac tissue, enhanced the antioxidant capacity, and mitigated inflammation. Metabolomics analysis revealed that the high-dose NT intervention improved cardiac tissue energy metabolism, potentially through activating the AMPK pathway, enhanced mitochondrial biogenesis, and increased TFAM protein expression.CONCLUSIONS: Together, these results indicate that exogenous NTs exert beneficial effects on the cardiac tissues of SAMP8 mice, potentially mitigating the cardiac aging process.PMID:39599637 | DOI:10.3390/nu16223851

Nutrients. 2024 Nov 8;16(22):3840. doi: 10.3390/nu16223840.ABSTRACTBACKGROUND: The gut-lung axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators.AIM: We conducted a pilot study to understand alterations in the gut-lung axis and to explore the effects of a probiotic in post-acute COVID-19 disease.METHODS: We included patients after severe COVID-19 disease (sCOV, n = 21) in a randomized, placebo-controlled trial to test the effect of a probiotic (Pro-Vi 5, Institute Allergosan, Graz, Austria) in a six-month intervention and used patients after mild disease (mCOV, n = 10) as controls, to compare the intestinal microbiome, metabolome, and patient-reported outcomes and biomarkers along the gut-lung axis at baseline and throughout probiotic intervention.RESULTS: Compared to mCOV patients, sCOV patients showed lower microbial richness, which was significantly improved by probiotic intervention. A reorganization of Ruminococcaceae and Lachnospiraceae taxa was observed in sCOV patients but remained unaffected by the intervention. Serum metabolome showed a dysregulation of lipoproteins in accordance with higher BMI and comorbidities in sCOV patients. HDL and LDL fractions/components were temporarily decreased in the probiotic group. Stool metabolome was altered at baseline in sCOV patients and an increase in L-DOPA after 3 months and butyrate after 6 months of intervention could be observed. Probiotics partially improved reduced quality of life and modulated altered immune responses in sCOV patients. Increased intestinal permeability at baseline remained unaffected.CONCLUSION: The study provides evidence of long-term alterations of the gut-lung axis after severe COVID-19 infection and suggests that probiotics can modulate the biomarkers of the gut-lung axis.PMID:39599626 | DOI:10.3390/nu16223840

Nutrients. 2024 Nov 8;16(22):3837. doi: 10.3390/nu16223837.ABSTRACTOBJECTIVES: Long-term Western diet-induced non-alcoholic steatohepatitis (NASH) can lead to liver cirrhosis and NASH-associated hepatocellular carcinoma, which are end-stage liver diseases. Meanwhile, NASH is associated with mental burden and worsens as the disease progresses. Atractylodes Macrocephala Koidz (AMK) is one of the main ingredients of Shenling Baizhu San, and the effect of Polysaccharide from AMK ameliorates (PAMK), as an important medicinal ingredient of AMK, on NASH and associated anxiety/depression-like behaviors is still unclear.METHODS: This study investigated the protective effect of PAMK on NASH and associated anxiety/depression-like behaviors through a Western diet-induced NASH mice model.RESULTS: showed that PAMK decreased the concentrations of liver TC, TG, and serum AST and ALT, improving glucose tolerance, and reducing liver steatosis and fibrosis. Moreover, the expression of liver IL-6, IL-1β, TNF-α, IL-18 and MCP-1 could be reduced by PAMK significantly. Additionally, PAMK decreased anxiety/depression-like behaviors and expression of IL-6, IL-1β, TNF-α, and MCP-1 in the hippocampus. 16S rRNA gene sequencing revealed that PAMK diminished the Firmicutes/Bacteroidetes ratio and abundance of Faecalibaculum_rodentium, and increased the abundance of Muribaculaceae. This might be related to gene abundance of Pentose, the glucuronate interconversions pathway and carbohydrate enzymes (GH1, GH4). Serum metabolomics suggested that PC (18:5e/2:0), PC (16:2e/2:0), Lysopc 20:4, PC (16:0/2:0), and LPC 19:0 upregulated significantly after PAMK intervention, together with the enrichment of carbon metabolism and Citrate cycle pathways specially.CONCLUSIONS: PAMK as a potential prebiotic ameliorated NASH and associated anxiety/depression-like behaviors in mice, probably by regulating Faecalibaculum_rodentium, carbohydrate enzymes and lipid metabolites.PMID:39599623 | DOI:10.3390/nu16223837

Pathogens. 2024 Oct 22;13(11):922. doi: 10.3390/pathogens13110922.ABSTRACTLiver fluke infections are acknowledged as diseases with global prevalence and significant implications for both veterinary and public health. The large American liver fluke, Fascioloides magna, is a significant non-native parasite introduced to Europe, threatening the survival of local wildlife populations. The aim of this study was to analyze differences in the serum proteome and metabolome between F. magna-infected and control red deer. Serum samples from red deer were collected immediately following regular hunting operations, including 10 samples with confirmed F. magna infection and 10 samples from healthy red deer. A proteomics analysis of the serum samples was performed using a tandem mass tag (TMT)-based quantitative approach, and a metabolomics analysis of the serum was performed using an untargeted mass spectrometry-based metabolomics approach. A knowledge-driven approach was applied to integrate omics data. Our findings demonstrated that infection with liver fluke was associated with changes in amino acid metabolism, energy metabolism, lipid metabolism, inflammatory host response, and related biochemical pathways. This study offers a comprehensive overview of the serum proteome and metabolome in response to F. magna infection in red deer, unveiling new potential targets for future research. The identification of proteins, metabolites, and related biological pathways enhances our understanding of host-parasite interactions and may improve current tools for more effective liver fluke control.PMID:39599475 | DOI:10.3390/pathogens13110922

Plants (Basel). 2024 Nov 15;13(22):3209. doi: 10.3390/plants13223209.ABSTRACTPhosphorus is crucial for plant growth and development, but excess fertilizer not absorbed by plants often binds with metal ions like iron and manganese, forming insoluble compounds that contribute to soil environmental pollution. This study investigates the impact of Burkholderia sp., a phosphate-solubilizing bacterium utilized as a biofertilizer, on the fertility of T. grandis soil, alongside the associated shifts in soil metabolites and their relationship with microbial communities after inoculation. The soil microbial community structures and metabolite profiles were analyzed via amplicon sequencing and high-resolution untargeted metabolomics. The inoculation of phosphate-solubilizing bacteria led to a significant (p < 0.05) enhancement in total phosphorus, potassium, and nitrogen concentrations in the soil, with a marked increase in available phosphorus in bulk soil (p < 0.05). Moreover, the microbial community structure exhibited significant shifts, particularly in the abundance of bacterial phyla such as Acidobacteria, Chloroflexi, Proteobacteria, and the fungal phylum Ascomycota. Metabolomic analysis revealed distinct metabolites, including fatty acids, hormones, amino acids, and drug-related compounds. Key microbial taxa such as Chloroflexi, Proteobacteria, Acidobacteria, Verrucomicrobia, Mucoromycota, and Ascomycota indirectly contributed to soil phosphorus metabolism by influencing these differential metabolites. In conclusion, the application of phosphate-solubilizing bacteria offers an innovative approach to improving soil quality in T. grandis, promoting phosphorus utilization efficiency, and enhancing soil ecosystem health by optimizing microbial communities and metabolite compositions.PMID:39599416 | DOI:10.3390/plants13223209

Plants (Basel). 2024 Nov 12;13(22):3171. doi: 10.3390/plants13223171.ABSTRACTThe early-ripening peach industry has undergone rapid development in the Panxi region of the Sichuan Basin in recent years. However, after the introduction of some new peach varieties to the high-altitude peach-producing areas in Panxi, the titratable acid content in peach fruit has significantly increased. This study compared the fruit quality indicators of early-ripening peach varieties cultivated in Xide County (a high-altitude peach-producing area) and Longquanyi District (a low-altitude peach-producing area) in Sichuan Province and analyzed the differences in organic acid metabolism by combining primary metabolomic and transcriptomic approaches. The results showed that the 'Zhongtaohongyu' fruit from the high-altitude peach-producing area had a much higher accumulation of malic acid and, accordingly, a significantly higher organic acid content than the other samples. The lower annual average temperature and stronger ultraviolet radiation in high-altitude peach-producing areas may lead to the increased expression of genes (PpNAD-ME1, PpNADP-ME3, and PpPEPC1) in the organic acid synthesis pathway and the decreased expression of genes (PpACO2, PpNAD-MDH2/3/4/5, and PpPEPCK2) in the organic acid degradation pathway in peach fruit, ultimately resulting in the accumulation of more organic acids. Among them, the downregulation of the key genes PpNAD-MDH3/4/5 involved in malic acid metabolism may be the main reason for the higher malic acid accumulation in peach fruit from high-altitude peach-producing areas. Overall, this study elucidates the mechanism by which environmental factors enhance the accumulation of organic acids in peach fruit from high-altitude peach-producing areas from a multi-omics perspective, as well as providing a theoretical basis for screening key genes involved in organic acid metabolism in peach fruit.PMID:39599380 | DOI:10.3390/plants13223171

Plants (Basel). 2024 Nov 9;13(22):3149. doi: 10.3390/plants13223149.ABSTRACTHyperaccumulators within the Noccaea genus possess many promising genetic and metabolic adaptations that could be potentially exploited to support phytoremediation efforts and/or crop improvement and biofortification. Although hyperaccumulation is very common in this genus, individual species display specific traits as they can accumulate different elements (e.g., zinc, cadmium, and/or nickel). Moreover, there appears to be some populational variability with natural selection increasing the metal tolerance in metallicolous populations. Therefore, employing robust methods, such as integrated analysis of the transcriptome and metabolome, is crucial for uncovering pivotal candidate genes and pathways orchestrating the response to metal stress in Noccaea hyperaccumulators. Our study highlights several species-specific traits linked to the detoxification of metals and metal-induced oxidative stress in hyperaccumulating N. praecox when compared to a closely related model species, N. caerulescens, when grown in the field. Transcriptome analysis revealed distinct differences between the three studied natural Noccaea populations. Notably, we observed several pathways frequently connected to metal stress, i.e., glutathione metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis, which were enriched. These differences were observed despite the relative evolutionary closeness of studied species, which emphasizes the importance of further expanding our knowledge on hyperaccumulators if we want to exploit their mechanisms for phytoremediation efforts or food quality improvements.PMID:39599358 | DOI:10.3390/plants13223149

Plants (Basel). 2024 Nov 8;13(22):3142. doi: 10.3390/plants13223142.ABSTRACTArsenate (AsV) is absorbed and accumulated by plants, which can affect their physiological activities, disrupt gene expression, alter metabolite content, and influence growth. Despite the potential of zinc oxide nanoparticles (ZnONPs) to mitigate the adverse effects of arsenic stress in plants, the underlying mechanisms of ZnONPs-mediated detoxification of AsV, as well as the specific metabolites and metabolic pathways involved, remain largely unexplored. In this study, we demonstrated root metabolomic profiling of soybean germinating seedlings subjected to 25 μmol L-1 arsenate (Na2HAsO4) and ZnONPs at concentrations of 25 μmol L-1 (ZnO25) and 50 μmol L-1 (ZnO50). The objective of this study was to examine the effects on soybean root metabolomics under AsV toxicity. Metabolomic analysis indicated that 453, 501, and 460 metabolites were significantly regulated in response to AsV, ZnO25, and ZnO50 treatments, respectively, compared to the control. Pathway analysis of the differentially regulated metabolites (DRMs) revealed that the tricarboxylic acid (TCA) cycle, glutathione metabolism, proline and aldarate metabolism, and arginine and proline metabolism were the most statistically enriched pathways in ZnONPs-supplemented plants. These findings suggest that ZnONPs enhance the tolerance response to AsV. Collectively, our results support the hypothesis that ZnONPs fertilization could be a potential strategy for improving soybean crop resilience under AsV stress.PMID:39599351 | DOI:10.3390/plants13223142