Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Immunogenic cell death inducers and PD-1 blockade as neoadjuvant therapy for rectal cancer

Mon, 21/10/2024 - 12:00
Oncoimmunology. 2024 Oct 17;13(1):2416558. doi: 10.1080/2162402X.2024.2416558. eCollection 2024.ABSTRACTImmuno-oncological cancer management is shifting to neoadjuvant treatments. In patients with gastrointestinal cancers, particularly locally advanced rectal cancer, neoadjuvant chemoimmunotherapy often induce complete responses, hence avoiding surgical intervention. Recent clinical trials indicate that combinations of oxaliplatin-based chemotherapy and PD-1/PD-L1-targeting immunotherapy can be safely administered before surgery with curative intent.PMID:39429516 | PMC:PMC11487966 | DOI:10.1080/2162402X.2024.2416558

Changes in Microbial Ecosystems and Serum Metabolomics by Diet Supplementation With Enramycin in Weaning Piglets

Mon, 21/10/2024 - 12:00
J Anim Physiol Anim Nutr (Berl). 2024 Oct 21. doi: 10.1111/jpn.14059. Online ahead of print.ABSTRACTAntibiotics are used in swine production for growth promotion and disease prevention, raising concerns about environmental contamination and antibiotic resistance. In this study, we investigated the effects of enramycin supplementation on piglet growth, gut microbiota and blood metabolites. Enramycin promotes piglet growth and temporarily reduces diarrhoea. Gut microbiota analysis revealed changes in microbial composition, including an increase in the abundance of Limosilactobacillus reuteri. Metabolomic analysis has identified elevated levels of dimethylglycine, a known growth-promoting factor, in the enramycin group. Liver gene expression analysis revealed increased mRNA levels of ALDH and dimethylglycine dehydrogenase, which are enzymes involved in dimethylglycine metabolism. The enramycin-treated group had a higher concentration of acetic acid in caecal contents, and their caecal acetic acid concentrations were positively correlated with the abundance of L. reuteri and the content of serum dimethylglycine, respectively. These findings suggest that the promotion effect of enramycin on piglet growth is related to the gut microbiota, blood metabolites and liver gene expression, which provide insights into antibiotic alternatives for swine production.PMID:39428819 | DOI:10.1111/jpn.14059

Assessment of amino acids and metabolites in the supernatant of stored concentrates blood from sickle cell trait (SCT) and reference (non-SCT) donors

Mon, 21/10/2024 - 12:00
Vox Sang. 2024 Oct 20. doi: 10.1111/vox.13753. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVES: Sickle cell trait (SCT) persons are significant donors, and discarding these blood units reduces their supplies, mainly in the third-world countries. This work focused on 12 metabolites associated with the red blood cell (RBC) storage lesion and 23 amino acids in the supernatants of packed RBC units from SCT and reference (non-SCT) donors stored in the same conditions.MATERIALS AND METHODS: All samples of RBC concentrates were collected and separated from the storage of Colsan (Beneficient Association of Blood Collection), where they were routinely processed and separated as packed RBC units and stored in the refrigerator (2°-6°C). The supernatant samples of each packed RBC bag were separated by centrifugation at days 1, 7, 14, 21, 28 and 35 of storage and kept at -80°C till the metabolite analysis together.RESULTS: The quantitation of metabolites and amino acids examined in the supernatant of SCT and reference donors showed no statistical differences along the cold storage. Lactic acid and malic acid releases occur in three phases during RBC storage. Basic and acid amino acids and corresponding amides have low and stable values during the first 14 days of storage, followed by a steep increase.CONCLUSION: Our metabolomic results give elements that seem not to contraindicate the transfusion of RBC with SCT, besides its more structural fragility.PMID:39428582 | DOI:10.1111/vox.13753

Low blood S-methyl-5-thioadenosine is associated with postoperative delayed neurocognitive recovery

Sun, 20/10/2024 - 12:00
Commun Biol. 2024 Oct 20;7(1):1356. doi: 10.1038/s42003-024-07086-5.ABSTRACTElderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR.PMID:39428444 | DOI:10.1038/s42003-024-07086-5

Unravelling the physiological and molecular mechanisms of leaf color change in Acer griseum through multi-omics analysis

Sun, 20/10/2024 - 12:00
Plant Physiol Biochem. 2024 Oct 16;216:109198. doi: 10.1016/j.plaphy.2024.109198. Online ahead of print.ABSTRACTPaperbark maple (Acer griseum), an endemic and endangered wild plant in China, has red-colored autumn leaves of high ornamental and garden application value. Leaf color change serves as a crucial indicator for evaluating garden tree aesthetics; however, research on A. griseum's leaf color change remains limited. This study aims to elucidate the physiological and molecular mechanisms underlying leaf color change in maple leaves through physiological, transcriptional, and metabolic assays. Data analysis encompasses gene expression levels and metabolite changes in three distinct states of maple leaves: green, half-red, and red. The progessive decrease of chlorophyll and carotenoids and the continuous accumulation of anthocyanidins caused a sharp change in leaf coloration, which was most drastic in the green to half-red period. Subsequently, targeted metabolomics analysis was performed, and a total of 71 anthocyanidins were detected, and the content of eight types of anthocyanidins increased significantly in the half-red and red periods, compared with that in the green period; of which the multiplicative difference was the largest for cyanidin-3,5-O diglucoside, delivering the largest multiplicative difference. Thus, it was plausible that cyanidin-3,5-O-diglucoside-dominated compoundswere likely to be the main metabolites associated with leaf reddening. Correlation analysis revealed that 12 key transcription factors (TFs) were significantly correlated with the anthocyanin-related metabolites and structural genes, which play important regulatory roles during the biosynthesis of anthocyanosides in A. griseum. These findings offered useful insights into the molecular basis of leaf color variation in A. griseum; providing valuable information to guide targeted genetic breeding and varietal improvement strategies.PMID:39427360 | DOI:10.1016/j.plaphy.2024.109198

A comprehensive study on the digestion, absorption, and metabolization of tropane alkaloids in human cell models

Sun, 20/10/2024 - 12:00
J Hazard Mater. 2024 Oct 17;480:136192. doi: 10.1016/j.jhazmat.2024.136192. Online ahead of print.ABSTRACTTropane alkaloids (TAs) are toxic compounds with potent anticholinergic effects. Herbal infusions are among the most contaminated food commodities; however, the fate of TAs after ingestion remains poorly understood. This study presents a comprehensive investigation into the absorption, and metabolism of five TAs (atropine, scopolamine, tropine, homatropine, and apoatropine) following the digestion of contaminated tea. In vitro human cell models were employed, including gastric (NCI-N87), intestinal (Caco-2:HT29-MTX), and hepatic (HEP-G2) cells. TAs were found to be highly absorbed in the intestinal epithelium, while gastric cells exhibited poor absorption. Metabolism was studied using a custom-made database, revealing that it occurs predominantly in intestinal cells, involving hydroxylation and methylation reactions. Cell metabolomics was conducted using annotation, fragment simulation, and statistical software platforms. Significant statistical differences were observed for 40 tentatively identified compounds. MetaboAnalyst 5.0 was employed to discern the most disturbed metabolic pathways, with amoniacids biosynthesis pathways and TCA cycles being the most affected. These pathways are involved in responses to cellular metabolic stress, neurotransmitter production, cellular energy generation, and the regulation of oxidative stress response. The findings of this study enhance our understanding of the fate of TAs after ingestion, their metabolization and their effects at the cellular level.PMID:39427354 | DOI:10.1016/j.jhazmat.2024.136192

Dried blood spots-based metabolomic analysis in preterm infants with necrotizing enterocolitis

Sun, 20/10/2024 - 12:00
J Matern Fetal Neonatal Med. 2024 Dec;37(1):2416610. doi: 10.1080/14767058.2024.2416610. Epub 2024 Oct 20.ABSTRACTOBJECTIVE: Necrotizing enterocolitis (NEC) is the leading cause of death among premature infants, and there is a lack of specific early diagnostic markers. Blood sampling is expected to better reflect pathophysiological and metabolic changes in systematic illness, but there is a risk of iatrogenic anemia, especially in premature infants. Dried blood spots technique seems to have important advantages compared to whole blood sampling as it requires only 12-15 μL as sample volume. This study aimed to investigate the special metabolomics of preterm neonates at high risk of NEC using dried blood spots.METHODS: Cases and controls were strictly matched 1:1. Dried blood spots (n = 32, 16 cases-16 controls) from newborn screening were subjected to LC-MS/MS. Metabolomic data were analyzed by orthogonal partial least squares-discriminant analysis (OPLS-DA) and univariate/multivariate statistical analysis.RESULTS: Compared to the control group, the NEC group had a significant reduction in seven amino acids (glycine, alanine, threonine, proline, ornithine, lysine, and asparagine).CONCLUSIONS: The metabolic profile of neonates with NEC differs significantly from that of controls, making possible their separation with the use of targeted (LC-MS/MS) dried blood spots-based metabolomic analysis. Seven specific markers were identified for early detection and intervention.PMID:39428341 | DOI:10.1080/14767058.2024.2416610

Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines

Sun, 20/10/2024 - 12:00
Chin J Nat Med. 2024 Oct;22(10):900-913. doi: 10.1016/S1875-5364(24)60687-4.ABSTRACTNatural medicines (NMs) are crucial for treating human diseases. Efficiently characterizing their bioactive components in vivo has been a key focus and challenge in NM research. High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) systems offer high sensitivity, resolution, and precision for conducting in vivo analysis of NMs. However, due to the complexity of NMs, conventional data acquisition, mining, and processing techniques often fail to meet the practical needs of in vivo NM analysis. Over the past two decades, intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for in vivo NM analysis. Consequently, improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument hardware. These improvements include enhanced instrument analysis sensitivity, expanded compound analysis coverage, intelligent identification, and characterization of nontargeted in vivo compounds, providing powerful technical means for studying the in vivo metabolism of NMs and screening for pharmacologically active components. This review summarizes the research progress on in vivo analysis strategies for NMs using intelligent MS data processing techniques reported over the past two decades. It discusses differences in compound structures, variations among biological samples, and the application of artificial intelligence (AI) neural network algorithms. Additionally, the review offers insights into the potential of in vivo tracking of NMs, including the screening of bioactive components and the identification of pharmacokinetic markers. The aim is to provide a reference for the integration and development of new technologies and strategies for future in vivo analysis of NMs.PMID:39428182 | DOI:10.1016/S1875-5364(24)60687-4

Omics detection and treatment of syphilis

Sun, 20/10/2024 - 12:00
Clin Chim Acta. 2024 Oct 18:120008. doi: 10.1016/j.cca.2024.120008. Online ahead of print.ABSTRACTTreponema pallidum is the source of the chronic systemic sexually transmitted illness syphilis. T. pallidum can evade immunity and spread. A hard chancre, enlarged lymph nodes, and a syphilis rash are the primary clinical signs. The condition may affect the nervous or cardiovascular system and even become fatal after being neglected. Omics technology is a cutting-edge technique that maps the entire regulatory network of gene and protein metabolism using high-throughput sequencing and other techniques, such as transcriptomics, proteomics, metabolomics, and genomics, to perform more efficient and methodical research on biological samples. Owing to the diverse and intricate biological roles and gene expression of T. pallidum, a single omics study is frequently insufficient and limited. This review focused on and summarized the use of several omics methods for investigating T. pallidum by referencing several different studies in the literature.PMID:39427935 | DOI:10.1016/j.cca.2024.120008

Polyvinyl chloride microplastics and drought co-exposure alter rice growth by affecting metabolomics and proteomics

Sun, 20/10/2024 - 12:00
Sci Total Environ. 2024 Oct 18:177002. doi: 10.1016/j.scitotenv.2024.177002. Online ahead of print.ABSTRACTMicroplastics, interacting with drought stress, have become threat to crops by altering soil environment. Currently, the effect of combined microplastic and drought stress on crop growth remain poorly understood. In this work, the mechanism of multi-stress responses was investigated under the exposure of polvinylchloride microplastic (PV) and drought (D) individually and in combination (DPV) on rice varieties Hanyou73 and Q280 through proteomics and metabolomic analysis. All treatments negatively affect chlorophyll content, antioxidant enzyme activities, rice grain composition, metabolome and proteomic profiling of both rice varieties. Full rice grain yield was decreased under all treatments except PV treatment in which it was increased in both rice varieties. DPV treatment shows the lowest grain yield and more adverse effects on metabolome by affecting glycerophospholipid metabolism, tryptophan metabolism and alanine, aspartate and glutamate metabolism. Soluble sugar contents were decreased in H73 but in Q280 increased by 159 % under DPV and 123 % in PV treatment, compared to their control group. The results from metabolomics illustrate that glycerophospholipid metabolism is commonly altered in both rice types under all treatments. PV and drought alone and in combination induce extensive alterations in proteomics of rice leaves especially impacting proteins related to binding, translation and photosynthetic process. The results reveal that PV and DPV treatments highly distort the abundance of metabolites and proteins in both rice types, demonstrating that microplastic toxicity effects on rice plants become more severe when combined with drought stress.PMID:39427893 | DOI:10.1016/j.scitotenv.2024.177002

Multiomics approach discloses lipids and metabolites profiles associated to Parkinson's disease stages and applied therapies

Sun, 20/10/2024 - 12:00
Neurobiol Dis. 2024 Oct 18:106698. doi: 10.1016/j.nbd.2024.106698. Online ahead of print.ABSTRACTProfiling circulating lipids and metabolites in Parkinson's disease (PD) patients could be useful not only to highlight new pathways affected in PD condition but also to identify sensitive and effective biomarkers for early disease detection and potentially effective therapeutic interventions. In this study we adopted an untargeted omics approach in three group of patients (No L-Dopa, L-Dopa and DBS) to disclose whether long-term levodopa treatment with or without deep brain stimulation (DBS) could reflect a characteristic lipidomic and metabolomic signature at circulating level. Our findings disclosed a wide up regulation of the majority of differentially regulated lipid species that increase with disease progression and severity. We found a relevant modulation of triacylglycerols and acyl-carnitines, together with an altered profile in adiponectin and leptin, that can differentiate the DBS treated group from the others PD patients. We found a highly significant increase of exosyl ceramides (Hex2Cer) and sphingoid bases (SPB) in PD patients mainly in DBS group (p < 0.0001), which also resulted in a highly accurate diagnostic performance. At metabolomic level, we found a wide dysregulation of pathways involved in the biosynthesis and metabolism of several amino acids acids. The most interesting finding was the identification of a specific modulation of L-glutamic acid in the three groups of patients. L-glutamate levels increased slightly in No L-Dopa and highly in L-Dopa patients while decreased in DBS, suggesting that DBS therapy might have a beneficial effect on the glutamatergic cascade. All together, these data provide novel insights into the molecular and metabolic alterations underlying PD therapy and might be relevant for PD prediction, diagnosis and treatment.PMID:39427845 | DOI:10.1016/j.nbd.2024.106698

Auricularia auricula polysaccharide alleviates cyclophosphamide-induced liver injury in mice involving remodeling of the gut bacteriome, mycobiome, and metabolome

Sun, 20/10/2024 - 12:00
Int J Biol Macromol. 2024 Oct 18:136703. doi: 10.1016/j.ijbiomac.2024.136703. Online ahead of print.ABSTRACTIn this study, a novel polysaccharide (AHP) from Auricularia auricula was isolated and purified, showing protective effects against CTX-induced liver injury in mice. To study the action mechanism of AHP, a liver injury model was established by intraperitoneally injection 80 mg/kg of CTX for 3 consecutive days. The focus was on how AHP regulated the gut bacteriome and mycobiome to help alleviate metabolic disorders associated with liver injury. Results showed that AHP amended liver injury by improving liver function, stabilizing oxidative stress homeostasis, reducing inflammatory invasion and activating Akt/GSK3β/Nrf-2/HO-1 signaling pathway. The 16S ribosomal DNA (16S rDNA) and Internal Transcribed Spacer-1 (ITS1) sequencing results demonstrated that AHP supplementation significantly restored the gut bacteriome and mycobiome composition in CTX-induced liver injury mice, by enriching the abundance of beneficial bacteriome (unclassified_Muribaculaceae, Faecalibaculum and Alloprevotella) and mycobiome (Fusarium), reducing the abundance of harmful bacteriome (Akkermanisa) and mycobiome (Fusicolla and Cladosporium). Analysis of untargeted metabolomics indicated that AHP altered the levels of metabolites associated with both bile acid and arachidonic acid metabolism, showing a significant connection to the AHP-regulated bacteriome and mycobiome. To conclude, the findings suggested that AHP was a viable and secure candidate for use as a hepatoprotective medication.PMID:39427797 | DOI:10.1016/j.ijbiomac.2024.136703

A newly identified protective role of C5aR1 in kidney tubules against toxin-induced acute kidney injury

Sun, 20/10/2024 - 12:00
Am J Pathol. 2024 Oct 18:S0002-9440(24)00367-5. doi: 10.1016/j.ajpath.2024.10.003. Online ahead of print.ABSTRACTAcute kidney injury (AKI) remains a major reason for hospitalization with limited therapeutic options. While complement activation is implicated in AKI, the role of C5a receptor 1 (C5aR1) in kidney tubular cells is unclear. We used aristolochic acid nephropathy (AAN) and folic acid nephropathy (FAN) models to establish the role of C5aR1 in kidney tubules during AKI in germline C5ar1-/- mice, myeloid cell-specific, and kidney tubule-specific C5ar1 knockout mice. After aristolochic acid and folic acid injection, C5ar1-/- mice had increased AKI severity and a higher degree of tubular injury. Macrophage depletion in C5ar1-/- mice or myeloid cell-specific C5ar1 deletion did not affect the outcomes of AA-induced AKI. RNA-sequencing data from RTECs showed that C5ar1 deletion was associated with the downregulation of mitochondrial metabolism and ATP production transcriptional pathways. Metabolic studies confirmed reduced mitochondrial membrane potential at baseline and increased mitochondrial oxidative stress after injury in C5ar1-/- RTECs. Moreover, C5ar1-/- RTECs had enhanced glycolysis, glucose uptake, and lactate production upon injury, corroborated by metabolomics analysis of kidneys from AAN mice. Kidney tubule-specific C5ar1 knockout mice recapitulated exacerbated AKI observed in C5ar1-/- mice in AAN and FAN. Our data indicate that C5aR1 signaling in kidney tubules exerts renoprotective effects against toxin-induced AKI by limiting overt glycolysis and maintaining mitochondrial function, revealing a novel link between the complement system and tubular cell metabolism.PMID:39427763 | DOI:10.1016/j.ajpath.2024.10.003

Metabolomics: Unveiling Biological Matrices in Precision Nutrition and Health

Sun, 20/10/2024 - 12:00
Clin Nutr ESPEN. 2024 Oct 18:S2405-4577(24)01486-4. doi: 10.1016/j.clnesp.2024.10.148. Online ahead of print.ABSTRACTPrecision nutrition, an expanding field at the intersection of nutrition science and personalized medicine, is rapidly evolving with metabolomics integration. Metabolomics, facilitated by advanced technologies like mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, facilitates comprehensive profiling of metabolites across diverse biological samples. From the perspective of health care systems, precision nutrition gains relevance due to the substantial impact of prevalent non-communicable diseases (NCDs) on societal well-being, which is directly linked with dietary habits and eating behavior. Furthermore, biomarker products derived from metabolomics have been utilized in Europe, the USA, and Brazil to understand metabolic dysregulations and tailor diets accordingly. Despite its burgeoning status, metabolomics holds great potential in revolutionizing nutritional science, particularly with the integration of artificial intelligence and machine learning, offering novel insights into personalized dietary interventions and disease prediction. This narrative review emphasizes the transformative impact of metabolomics in precision and delineates avenues for future research and application, paving the way for a more tailored and practical approach to nutrition management.PMID:39427750 | DOI:10.1016/j.clnesp.2024.10.148

Integrated anti-fatigue effects of polysaccharides and small molecules coexisting in water extracts of ginseng: gut microbiota-mediated mechanisms

Sun, 20/10/2024 - 12:00
J Ethnopharmacol. 2024 Oct 18:118958. doi: 10.1016/j.jep.2024.118958. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Both clinical and animal studies have demonstrated that ginseng has curative effects on fatigue. Our previous study found that water extracts of ginseng (WEG) could significantly mitigate exercise-induced fatigue (EF). Notably, polysaccharides (GP) and small molecules (GS, mainly ginsenosides) coexist in WEG. Whether and how GP and GS contribute to the anti-EF effects of WEG remains unknown.AIM OF THE STUDY: To evaluate the contribution of GP and GS to the anti-EF effects of WEG and clarify the potential gut microbiota-mediated mechanisms.MATERIALS AND METHODS: Firstly, the anti-EF effects of WEG, GP and GS were comparatively investigated by determining fatigue phenotypes (energy metabolism and oxidative stress parameters), gut microbiota composition as well as exogenous and endogenous metabolites in EF modeling rats. Then, the gut microbiota mediated mechanisms were verified by antibiotics (ABX) intervention and fecal microbial transplantation (FMT).RESULTS: GP, GS and WEG each exhibited distinct anti-EF effects in differentially improving EF-induced energy metabolism abnormality and oxidative stress, reshaping gut microbiota composition, and elevating systemic metabolites. Notably, WEG showed stronger anti-EF effects than both GP and GS, characterized by better alleviation of disturbances in energy metabolism (e.g. Glc) and oxidative stress parameters (e.g. SOD), regulation of gut microbiota homeostasis (e.g. enriching the genus Coprococcus and species Collinsella provencensis etc.), as well as increases in exogenous secondary ginsenosides (e.g. 20(S)-Rg3, 20(R)-Rg3, CK), endogenous bile acids (BAs) (e.g. CA, DCA, LCA), and short chain fatty acids (SCFAs) (e.g. butyric acid). The stronger anti-EF effects of WEG compared to GP and GS could be abolished by ABX intervention, and transferred by FMT.CONCLUSION: GP and GS could collectively contribute to the anti-EF effects of WEG through integrated actions. Gut microbiota mediate the integrated anti-EF effects of GP and GS in WEG, potentially by regulating the levels of exogenous bioactive secondary ginsenosides, as well as endogenous BAs and SCFAs, thereby alleviating fatigue-related energy metabolic abnormalities and oxidative stress.PMID:39427741 | DOI:10.1016/j.jep.2024.118958

A two-front nutrient supply environment fuels small intestinal physiology through differential regulation of nutrient absorption and host defense

Sun, 20/10/2024 - 12:00
Cell. 2024 Oct 19:S0092-8674(24)00903-6. doi: 10.1016/j.cell.2024.08.012. Online ahead of print.ABSTRACTThe small intestine contains a two-front nutrient supply environment created by luminal dietary and microbial metabolites (enteral side) and systemic metabolites from the host (serosal side). Yet, it is unknown how each side contributes differentially to the small intestinal physiology. Here, we generated a comprehensive, high-resolution map of the small intestinal two-front nutrient supply environment. Using in vivo tracing of macronutrients and spatial metabolomics, we visualized the spatiotemporal dynamics and cell-type tropism in nutrient absorption and the region-specific metabolic heterogeneity within the villi. Specifically, glutamine from the enteral side fuels goblet cells to support mucus production, and the serosal side loosens the epithelial barrier by calibrating fungal metabolites. Disorganized feeding patterns, akin to the human lifestyle of skipping breakfast, increase the risk of metabolic diseases by inducing epithelial memory of lipid absorption. This study improves our understanding of how the small intestine is spatiotemporally regulated by its unique nutritional environment.PMID:39427662 | DOI:10.1016/j.cell.2024.08.012

Targeting Lipid Metabolism in Obese Asthma: Perspectives and Therapeutic Opportunities

Sun, 20/10/2024 - 12:00
Int Arch Allergy Immunol. 2024 Oct 18:1-15. doi: 10.1159/000540405. Online ahead of print.ABSTRACTBACKGROUND: Obese asthma represents a unique phenotype of asthma characterized by severe symptoms, poor medication controls, increased frequency of exacerbations, and an overall diminished quality of life. Numerous factors, including the complex interactions between environment, mechanical processes, inflammatory responses, and metabolites disturbance, contribute to the onset of obese asthma.SUMMARY: Notably, multiple metabolomics studies in the last several years have revealed the significant abnormalities in lipid metabolism among obese asthmatic patients. Several bioactive lipid messengers participate in the development of obese asthma has also been observed. Here, we present and discuss the latest advances regarding how bioactive lipid molecules contribute to the pathogenic process and mechanisms underlying obese asthma. The key roles of potentially significant effector cells and the pathways by which they respond to diverse lipid metabolites are also described. We finally summarize current lipid-related therapeutic options for the treatment of obese asthma and discuss their application prospects.KEY MESSAGES: This review underscores the impacts of abnormal lipid metabolism in the etiopathogenesis of obese asthma and asks for further investigation to elucidate the intricate correlations among lipids, obesity, and asthma.PMID:39427653 | DOI:10.1159/000540405

SFMBT2 regulates plumage color via serum metabolites in Chinese Anyi tile-like gray chickens

Sun, 20/10/2024 - 12:00
Poult Sci. 2024 Oct 9;103(12):104391. doi: 10.1016/j.psj.2024.104391. Online ahead of print.ABSTRACTPlumage color is an important characteristic of chicken breeds, and molecular genetic research is significant for resource conservation and product quality control. Anyi tile-like gray chicken is a high-quality local chicken breed resource generated through long-term natural selection and artificial breeding in China. However, the molecular mechanisms underlying plumage color formation in Anyi tile-like gray chickens remain unclear. In this study, nontargeted liquid chromatography and tandem mass spectrometry (LC-MS/MS) was performed to identify serum metabolites associated with plumage color in 93 Anyi tile-like gray chickens, including 60 tile-like gray and 33 black chickens. Notably, 12 serum metabolites were significantly enriched in Anyi tile-like gray chickens, including deoxyuridine and inosine, which were the key biomarkers distinguishing tile-like gray chickens from black chickens. Additionally, nine serum metabolites were significantly enriched in black chickens. Moreover, we identified 225 significant SNPs (P < 9.71 × 10-8) on chromosomes 1, 2, 3, 4, 11, 15, and 21 that were associated with deoxyuridine, inosine, 3-hydroxybenzoic acid, and L-methionine S-oxide through metabolome genome-wide association studies (mGWAS). Importantly, chromosome 1 harbored a region, 172.79-kb, which was the most likely quantitative trait locus (QTL) interval. RNA sequencing (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that SFMBT2 was the only differentially expressed gene in the QTL interval, and its expression was correlated with the abundance of specific serum metabolites. Conclusively, SFMBT2-mediated changes in serum metabolites contribute to plumage color development in Anyi tile-like gray chicken. This study provides important insights into the interaction between serum metabolites and host genes, and offers a theoretical basis for the breeding of Anyi tile-like gray chickens.PMID:39427420 | DOI:10.1016/j.psj.2024.104391

Effects of dietary paddy rice on the growth, serum biochemistry, intestinal development, microbiota, and metabolism of young laying ducks in a rice-duck-crayfish farming system

Sun, 20/10/2024 - 12:00
Poult Sci. 2024 Sep 28;103(12):104369. doi: 10.1016/j.psj.2024.104369. Online ahead of print.ABSTRACTThis study investigated the effects of feeding paddy rice on the physiology, metabolism, and gut microbiota of ducks in a rice-duck-crayfish (RDC) system. A total of 540 ducks (20-days-old) were randomly divided into 3 groups with 3 replicates and 60 ducks per replicate. The 40-d experiment involved 3 diet treatments: a complete diet (CD), 50% paddy rice + 50% complete diet (RCD), and 100% paddy rice diet (RD). Results show that feeding paddy rice did not significantly affect duck growth, the final weight in the RD group was reduced by 5%, and the feed-to-gain ratio increased by 7% compared to the CD group. Additionally, compared with the CD group, the keel length, gizzard and proventriculus indices, and serum high-density lipoprotein levels increased (P < 0.05), and duodenal villus height and ileal crypt depth (P < 0.05) reduced in the RD group and ileal villus height decreased in the RCD group (P < 0.05). Compared with the CD group, the cecal abundance of Bacteroidota, Prevotellaceae_Ga6A1_group, and Prevotellaceae_NK3B31_group decreased in the RD group (P < 0.05) while the abundance of Firmicutes, Megamonas and Faecalibacterium increased (P < 0.05). Metabolome analysis revealed that serum citric acid increased (P < 0.05) in the RCD and RD groups, whereas cytidine, cytosine, and 4-aminobutyric acid decreased (P < 0.05) in the RD group. In conclusion, these preliminary results suggest that paddy rice supplementation under an RDC system had no significant effect on duck growth, but it did cause changes in intestinal morphology, microbiota, and serum metabolic profiles. However, it is important to note that the limited overall number of replicates in this study contributed to a certain degree of high variance. While the growth differences among groups were not statistically significant, the full replacement of paddy rice still poses potential performance losses. In practical applications, this finding provides a reference for the RDC system, but further validation through larger-scale trials is required.PMID:39427418 | DOI:10.1016/j.psj.2024.104369

COLMAR1d: A Web Server for Automated, Quantitative One-Dimensional Nuclear Magnetic Resonance-Based Metabolomics at Arbitrary Magnetic Fields

Sun, 20/10/2024 - 12:00
Anal Chem. 2024 Oct 20. doi: 10.1021/acs.analchem.4c02688. Online ahead of print.ABSTRACTThe field of metabolomics, which is quintessential in today's omics research, involves the large-scale detection, identification, and quantification of small-molecule metabolites in a wide range of biological samples. Nuclear magnetic resonance spectroscopy (NMR) has emerged as a powerful tool for metabolomics due to its high resolution, reproducibility, and exceptional quantitative nature. One of the key bottlenecks of metabolomics studies, however, remains the accurate and automated analysis of the resulting NMR spectra with good accuracy and minimal human intervention. Here, we present the COLMAR1d platform, consisting of a public web server and an optimized database, for one-dimensional (1D) NMR-based metabolomics analysis to address these challenges. The COLMAR1d database comprises more than 480 metabolites from GISSMO enabling a database query of spectra measured at arbitrary magnetic field strengths, as is demonstrated for spectra acquired between 1H resonance frequencies of 80 MHz and 1.2 GHz of mouse serum, DMEM cell growth medium, and wine. COLMAR1d combines the GISSMO metabolomics database concept with the latest tools for automated processing, spectral deconvolution, database querying, and globally optimized mixture analysis for improved accuracy and efficiency. By leveraging advanced computational algorithms, COLMAR1d offers a user-friendly, automated platform for quantitative 1D NMR-based metabolomics analysis allowing a wide range of applications, including biomarker discovery, metabolic pathway elucidation, and integration with multiomics strategies.PMID:39427262 | DOI:10.1021/acs.analchem.4c02688

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