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

Metabolic and oxidative stress response of sea cucumber Apostichopus japonicus exposed to acute high concentration of bisphenol AF

Mon, 14/08/2023 - 12:00
Aquat Toxicol. 2023 Aug 11;262:106654. doi: 10.1016/j.aquatox.2023.106654. Online ahead of print.ABSTRACTBisphenols are known as endocrine disruptor that affect the development, and growth of marine creatures, including human. There were plenty of manuscripts evaluated the toxicology of bisphenol A (BPA) and its analogues such as bisphenol F (BPF), bisphenol AF (BPAF), and bisphenol S (BPS), but limits of them studied the effects of bisphenol analogues on echinoderms. In this study, we used metabolomics to investigate the metabolic response of sea cucumber (Apostichopus japonicus) exposed to BPAF, and the activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were determined. The results demonstrated alterations in lipid metabolism, glycerophospholipid metabolism, and biosynthesis of amino acids following BPAF treatment. Sea cucumbers upregulated the glycerophospholipid metabolism to repair the destruction of intestine cellular homeostasis. Six metabolites were selected as the potential biomarkers for the exposure of BPAF. This study revealed the metabolic response and oxidative response of sea cucumber arising from BPAF exposure, and provided theoretical support for the risk assessment of bisphenol analogues on economically important echinoderms, such as A. japonicus.PMID:37579560 | DOI:10.1016/j.aquatox.2023.106654

Shaping the tumor immune microenvironment of SCLC: Mechanisms, and opportunities for immunotherapy

Mon, 14/08/2023 - 12:00
Cancer Treat Rev. 2023 Aug 7;120:102606. doi: 10.1016/j.ctrv.2023.102606. Online ahead of print.ABSTRACTSmall-cell lung cancer (SCLC) is a very aggressive neuroendocrine tumor with a poor prognosis. Whereas immunotherapy has emerged as a promising approach for treating SCLC, its unique tumor immune microenvironment (TIME) might limit patient responses. To fully characterize the TIME and understand the mechanism of its formation with respect to SCLC is crucial. The recent rapid development of multi-omics technologies has rapidly advanced knowledge of TIME features and the regulatory mechanisms associated with SCLC. This review summarizes the TIME features of SCLC as well as shaping the TIME according to the genomics, epigenomics, and metabolomics of tumors. Future opportunities and challenges for immunotherapy are also discussed.PMID:37579532 | DOI:10.1016/j.ctrv.2023.102606

Aggregated Molecular Phenotype Scores: Enhancing Assessment and Visualization of Mass Spectrometry Imaging Data for Tissue-Based Diagnostics

Mon, 14/08/2023 - 12:00
Anal Chem. 2023 Aug 14. doi: 10.1021/acs.analchem.3c02389. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) has gained increasing popularity for tissue-based diagnostics due to its ability to identify and visualize molecular characteristics unique to different phenotypes within heterogeneous samples. Data from MSI experiments are often assessed and visualized using various supervised and unsupervised statistical approaches. However, these approaches tend to fall short in identifying and concisely visualizing subtle, phenotype-relevant molecular changes. To address these shortcomings, we developed aggregated molecular phenotype (AMP) scores. AMP scores are generated using an ensemble machine learning approach to first select features differentiating phenotypes, weight the features using logistic regression, and combine the weights and feature abundances. AMP scores are then scaled between 0 and 1, with lower values generally corresponding to class 1 phenotypes (typically control) and higher scores relating to class 2 phenotypes. AMP scores, therefore, allow the evaluation of multiple features simultaneously and showcase the degree to which these features correlate with various phenotypes. Due to the ensembled approach, AMP scores are able to overcome limitations associated with individual models, leading to high diagnostic accuracy and interpretability. Here, AMP score performance was evaluated using metabolomic data collected from desorption electrospray ionization MSI. Initial comparisons of cancerous human tissues to their normal or benign counterparts illustrated that AMP scores distinguished phenotypes with high accuracy, sensitivity, and specificity. Furthermore, when combined with spatial coordinates, AMP scores allow visualization of tissue sections in one map with distinguished phenotypic borders, highlighting their diagnostic utility.PMID:37579019 | DOI:10.1021/acs.analchem.3c02389

Evaluation of Data-Dependent MS/MS Acquisition Parameters for Non-Targeted Metabolomics and Molecular Networking of Environmental Samples: Focus on the Q Exactive Platform

Mon, 14/08/2023 - 12:00
Anal Chem. 2023 Aug 14. doi: 10.1021/acs.analchem.3c01202. Online ahead of print.ABSTRACTNon-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely used tool for metabolomics analysis, enabling the detection and annotation of small molecules in complex environmental samples. Data-dependent acquisition (DDA) of product ion spectra is thereby currently one of the most frequently applied data acquisition strategies. The optimization of DDA parameters is central to ensuring high spectral quality, coverage, and number of compound annotations. Here, we evaluated the influence of 10 central DDA settings of the Q Exactive mass spectrometer on natural organic matter samples from ocean, river, and soil environments. After data analysis with classical and feature-based molecular networking using MZmine and GNPS, we compared the total number of network nodes, multivariate clustering, and spectrum quality-related metrics such as annotation and singleton rates, MS/MS placement, and coverage. Our results show that automatic gain control, microscans, mass resolving power, and dynamic exclusion are the most critical parameters, whereas collision energy, TopN, and isolation width had moderate and apex trigger, monoisotopic selection, and isotopic exclusion minor effects. The insights into the data acquisition ergonomics of the Q Exactive platform presented here can guide new users and provide them with initial method parameters, some of which may also be transferable to other sample types and MS platforms.PMID:37578818 | DOI:10.1021/acs.analchem.3c01202

Stratifying Ferroptosis Sensitivity in Cells and Tissues with PALP

Mon, 14/08/2023 - 12:00
Methods Mol Biol. 2023;2712:9-17. doi: 10.1007/978-1-0716-3433-2_2.ABSTRACTFerroptosis is emerging as a promising strategy for suppressing multiple types of human cancers. Rapid and accurate assessment of the relative sensitivity to ferroptosis in biological samples will accelerate the development of ferroptosis-targeted therapies. We previously demonstrated that photochemical activation of membrane lipid peroxidation (PALP) that uses high-power lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation can efficiently report ferroptosis sensitivity in live cells and tissues in situ. Here, we describe the experimental details for PALP analysis, including preparation of tissue sections, preparation of fluorescent lipid peroxidation reporter, sample staining, lipid peroxidation induced by laser source, and data processing. We envision predicting the relative sensitivity to ferroptosis of cellular and tissue samples is potentially useful for basic research and clinical investigations.PMID:37578692 | DOI:10.1007/978-1-0716-3433-2_2

Gut microbiome-serum metabolic profiles: insight into the hypoglycemic effect of <em>Porphyra haitanensis</em> glycoprotein on hyperglycemic mice

Mon, 14/08/2023 - 12:00
Food Funct. 2023 Aug 14. doi: 10.1039/d3fo02040a. Online ahead of print.ABSTRACTThe hypoglycemic activity of natural algal glycoproteins has attracted interest, but studies of their mechanism of regulating glucose metabolism are lacking. This study investigated the hypoglycemic activity of Porphyra haitanensis glycoprotein (PG) in a mouse hyperglycemia model. The underlying mechanism was elucidated by monitoring changes in the gut microbiome and untargeted serum metabolomics. The results indicated that 30-300 mg kg-1 PG regulated blood glucose levels by increasing insulin secretion, reducing glycated hemoglobin, and improving streptozotocin-induced hyperglycemia in a concentration-dependent manner. In particular, 300 mg kg-1 PG decreased fasting blood glucose by 63.11% and glycosylated hemoglobin by 24.50% and increased insulin secretion by 163.97%. The mechanism of the improvement of hyperglycemia by PG may involve regulating beneficial intestinal bacteria (e.g., norank_f__Muribaculaceae and Lachnospiraceae) and altering the serum metabolic profile (e.g., upregulation of hypotaurine, 3-hydroxy-2-naphthoic acid, and L-glycine), to regulate taurine and hypotaurine, the TCA cycle, AMPK, and pyruvate metabolism. Our findings supported the development of Porphyra haitanensis and its glycoprotein as novel natural antidiabetic compounds to regulate the glycemic balance.PMID:37578326 | DOI:10.1039/d3fo02040a

Methodology to Metabolically Inactivate Bacteria for Caenorhabditis elegans Research

Mon, 14/08/2023 - 12:00
J Vis Exp. 2023 Jul 28;(197). doi: 10.3791/65775.ABSTRACTCaenorhabditis elegans is a common model organism for research in genetics, development, aging, metabolism, and behavior. Because C. elegans consume a diet of live bacteria, the metabolic activity of their food source can confound experiments looking for the direct effects of various interventions on the worm. To avoid the confounding effects of bacterial metabolism, C. elegans researchers have used multiple methods to metabolically inactivate bacteria, including ultraviolet (UV)-irradiation, heat-killing, and antibiotics. UV treatment is relatively low-throughput and cannot be used in liquid culture because each plate must be examined for successful bacterial killing. A second treatment method, heat-killing, negatively affects the texture and nutritional quality of the bacteria, leading to the developmental arrest of C. elegans. Finally, antibiotic treatment can directly alter C. elegans physiology in addition to preventing bacterial growth. This manuscript describes an alternative method to metabolically inactivate bacteria using paraformaldehyde (PFA). PFA treatment cross-links proteins within bacterial cells to prevent metabolic activity while preserving cellular structure and nutritional content. This method is high-throughput and can be used in liquid culture or solid plates, as testing one plate of PFA-treated bacteria for growth validates the whole batch. Metabolic inactivation through PFA treatment can be used to eliminate the confounding effects of bacterial metabolism on studies of drug or metabolite supplementation, stress resistance, metabolomics, and behavior in C. elegans.PMID:37578251 | DOI:10.3791/65775

Metabolomic changes associated with acquired resistance to <em>Ixodes scapularis</em>

Mon, 14/08/2023 - 12:00
bioRxiv. 2023 Jul 31:2023.07.31.551287. doi: 10.1101/2023.07.31.551287. Preprint.ABSTRACTGuinea pigs repeatedly exposed to Ixodes scapularis develop acquired resistance to the ticks (ATR). The molecular mechanisms of ATR have not been fully elucidated, and partially involve immune responses to proteins in tick saliva. In this study, we examined the metabolome of sera of guinea pigs during the development of ATR. Induction of components of the tyrosine metabolic pathway, including hydroxyphenyllactic acid (HPLA), were associated with ATR. We therefore administered HPLA to mice, an animal that does not develop ATR, and exposed the animals to I. scapularis . We also administered nitisinone, a known inhibitor of tyrosine degradation, to another group of mice. The mortality of I. scapularis that fed on mice given HPLA or nitisinone was 26% and 72% respectively, compared with 2% mortality among ticks that fed on control animals. These data indicate that metabolic changes that occur after tick bites contribute to ATR.PMID:37577710 | PMC:PMC10418055 | DOI:10.1101/2023.07.31.551287

FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse

Mon, 14/08/2023 - 12:00
bioRxiv. 2023 Aug 5:2023.08.03.551853. doi: 10.1101/2023.08.03.551853. Preprint.ABSTRACTMitochondria are not only essential for energy production in eukaryocytes but also a key regulator of intracellular signaling. Here, we report an unappreciated role of mitochondria in regulating cytosolic protein translation in skeletal muscle cells (myofibers). We show that the expression of mitochondrial protein FAM210A (Family With Sequence Similarity 210 Member A) is positively associated with muscle mass in mice and humans. Muscle-specific Myl1 Cre -driven Fam210a knockout ( Fam210a MKO ) in mice reduces mitochondrial density and function, leading to progressive muscle atrophy and premature death. Metabolomic and biochemical analyses reveal that Fam210a MKO reverses the oxidative TCA cycle towards the reductive direction, resulting in acetyl-CoA accumulation and hyperacetylation of cytosolic proteins. Specifically, hyperacetylation of several ribosomal proteins leads to disassembly of ribosomes and translational defects. Transplantation of Fam210a MKO mitochondria into wildtype myoblasts is sufficient to elevate protein acetylation in recipient cells. These findings reveal a novel crosstalk between the mitochondrion and ribosome mediated by FAM210A.PMID:37577696 | PMC:PMC10418219 | DOI:10.1101/2023.08.03.551853

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data

Mon, 14/08/2023 - 12:00
Res Sq. 2023 Aug 3:rs.3.rs-3189768. doi: 10.21203/rs.3.rs-3189768/v1. Preprint.ABSTRACTMicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms' role in ecology and human health.PMID:37577622 | PMC:PMC10418563 | DOI:10.21203/rs.3.rs-3189768/v1

Mass spectrometry-based multi-omics identifies metabolic signatures of sarcopenia in rhesus monkey skeletal muscle

Mon, 14/08/2023 - 12:00
bioRxiv. 2023 Jul 31:2023.07.31.551315. doi: 10.1101/2023.07.31.551315. Preprint.ABSTRACTSarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in omics technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified numerous proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified multiple metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offer new insights into the molecular mechanism underlying sarcopenia for the evaluation and monitoring of therapeutic treatment of sarcopenia.PMID:37577600 | PMC:PMC10418093 | DOI:10.1101/2023.07.31.551315

Editorial: Role of starters on the safety of fermented food products

Mon, 14/08/2023 - 12:00
Front Microbiol. 2023 Jul 28;14:1260403. doi: 10.3389/fmicb.2023.1260403. eCollection 2023.NO ABSTRACTPMID:37577433 | PMC:PMC10420064 | DOI:10.3389/fmicb.2023.1260403

Unveiling the spatial distribution and molecular mechanisms of terpenoid biosynthesis in <em>Salvia miltiorrhiza</em> and <em>S. grandifolia</em> using multi-omics and DESI-MSI

Mon, 14/08/2023 - 12:00
Hortic Res. 2023 May 31;10(7):uhad109. doi: 10.1093/hr/uhad109. eCollection 2023 Jul.ABSTRACTSalvia miltiorrhiza and S. grandifolia are rich in diterpenoids and have therapeutic effects on cardiovascular diseases. In this study, the spatial distribution of diterpenoids in both species was analyzed by a combination of metabolomics and mass spectrometry imaging techniques. The results indicated that diterpenoids in S. miltiorrhiza were mainly abietane-type norditerpenoid quinones with a furan or dihydrofuran D-ring and were mainly distributed in the periderm of the roots, e.g. cryptotanshinone and tanshinone IIA. The compounds in S. grandifolia were mainly phenolic abietane-type tricyclic diterpenoids with six- or seven-membered C-rings, and were widely distributed in the periderm, phloem, and xylem of the roots, e.g. 11-hydroxy-sugiol, 11,20-dihydroxy-sugiol, and 11,20-dihydroxy-ferruginol. In addition, the leaves of S. grandifolia were rich in tanshinone biosynthesis precursors, such as 11-hydroxy-sugiol, while those of S. miltiorrhiza were rich in phenolic acids. Genes in the upstream pathway of tanshinone biosynthesis were highly expressed in the root of S. grandifolia, and genes in the downstream pathway were highly expressed in the root of S. miltiorrhiza. Here, we describe the specific tissue distributions and mechanisms of diterpenoids in two Salvia species, which will facilitate further investigations of the biosynthesis of diterpenoids in plant synthetic biology.PMID:37577405 | PMC:PMC10419090 | DOI:10.1093/hr/uhad109

Dopamine alleviates cadmium stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed by high-throughput sequencing and soil metabolomics

Mon, 14/08/2023 - 12:00
Hortic Res. 2023 May 22;10(7):uhad112. doi: 10.1093/hr/uhad112. eCollection 2023 Jul.ABSTRACTDopamine has demonstrated promise as a stress-relief substance. However, the function of dopamine in Cd tolerance and its mechanism remains largely unknown. The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil. The results indicated that dopamine significantly reduced reactive oxygen species (ROS) and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system, enhancement of photosynthetic capacity, and regulation of gene expression related to Cd absorption and detoxification. The richness of the rhizosphere microbial community increased, and community composition and assembly were affected by dopamine treatment. Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment, while the keystone species shifted. Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment, suggesting that dopamine induced plants to recruit potentially beneficial microorganisms (Pseudoxanthomonas, Aeromicrobium, Bradyrhizobium, Frankia, Saccharimonadales, Novosphingobium, and Streptomyces) to resist Cd stress. The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation, suggesting that potentially beneficial microorganisms may be attracted by several metabolites (L-threonic acid, profenamine, juniperic acid and (3β,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid). Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed. This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.PMID:37577402 | PMC:PMC10419553 | DOI:10.1093/hr/uhad112

Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy

Mon, 14/08/2023 - 12:00
J Pharm Anal. 2023 Jul;13(7):776-787. doi: 10.1016/j.jpha.2023.02.010. Epub 2023 Feb 28.ABSTRACTAgainst tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy. However, metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity. Herein, choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types, and a choline-modified strategy for small molecule-drug conjugates (SMDCs) design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy, instead of directly inhibiting choline metabolism. As a proof-of-concept, choline-modified SMDCs were designed, screened, and investigated for their druggability in vitro and in vivo. This strategy improved tumor targeting, preserved tumor inhibition and reduced toxicity of paclitaxel, through targeted drug delivery to tumor by highly expressed choline transporters, and site-specific release by carboxylesterase. This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.PMID:37577390 | PMC:PMC10422108 | DOI:10.1016/j.jpha.2023.02.010

Dissecting the brain with spatially resolved multi-omics

Mon, 14/08/2023 - 12:00
J Pharm Anal. 2023 Jul;13(7):694-710. doi: 10.1016/j.jpha.2023.04.003. Epub 2023 Apr 10.ABSTRACTRecent studies have highlighted spatially resolved multi-omics technologies, including spatial genomics, transcriptomics, proteomics, and metabolomics, as powerful tools to decipher the spatial heterogeneity of the brain. Here, we focus on two major approaches in spatial transcriptomics (next-generation sequencing-based technologies and image-based technologies), and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics. Furthermore, we discuss their applications in neuroscience, including building the brain atlas, uncovering gene expression patterns of neurons for special behaviors, deciphering the molecular basis of neuronal communication, and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders. However, further efforts are still needed toward the integrative application of multi-omics technologies, including the real-time spatial multi-omics analysis in living cells, the detailed gene profile in a whole-brain view, and the combination of functional verification.PMID:37577383 | PMC:PMC10422112 | DOI:10.1016/j.jpha.2023.04.003

Diarrheal-associated gut dysbiosis in cancer and inflammatory bowel disease patients is exacerbated by <em>Clostridioides difficile</em> infection

Mon, 14/08/2023 - 12:00
Front Cell Infect Microbiol. 2023 Jul 27;13:1190910. doi: 10.3389/fcimb.2023.1190910. eCollection 2023.ABSTRACTINTRODUCTION: Low diversity gut dysbiosis can take different forms depending on the disease context. In this study, we used shotgun metagenomic sequencing and gas chromatography-mass spectrometry (GC-MS) to compared the metagenomic and metabolomic profiles of Clostridioides (Clostridium) difficile diarrheal cancer and inflammatory bowel disease (IBD) patients and defined the additive effect of C. difficile infection (CDI) on intestinal dysbiosis.RESULTS: The study cohort consisted of 138 case-mix cancer patients, 43 IBD patients, and 45 healthy control individuals. Thirty-three patients were also infected with C. difficile. In the control group, three well-known enterotypes were identified, while the other groups presented with an additional Escherichia-driven enterotype. Bacterial diversity was significantly lower in all groups than in healthy controls, while the highest level of bacterial species richness was observed in cancer patients. Fifty-six bacterial species had abundance levels that differentiated diarrheal patient groups from the control group. Of these species, 52 and 4 (Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, and Ruminococcus gnavus) were under-represented and over-represented, respectively, in all diarrheal patient groups. The relative abundances of propionate and butyrate were significantly lower in fecal samples from IBD and CDI patients than in control samples. Isobutyrate, propanate, and butyrate concentrations were lower in cancer, IBD, and CDI samples, respectively. Glycine and valine amino acids were over- represented in diarrheal patients.CONCLUSION: Our data indicate that different external and internal factors drive comparable profiles of low diversity dysbiosis. While diarrheal-related low diversity dysbiosis may be a consequence of systemic cancer therapy, a similar phenotype is observed in cases of moderate to severe IBD, and in both cases, dysbiosis is exacerbated by incidence of CDI.PMID:37577378 | PMC:PMC10413277 | DOI:10.3389/fcimb.2023.1190910

Structure of gut microbiota and characteristics of fecal metabolites in patients with lung cancer

Mon, 14/08/2023 - 12:00
Front Cell Infect Microbiol. 2023 Jul 27;13:1170326. doi: 10.3389/fcimb.2023.1170326. eCollection 2023.ABSTRACTOBJECTIVE: The gut micro-biome plays a pivotal role in the progression of lung cancer. However, the specific mechanisms by which the intestinal microbiota and its metabolites are involved in the lung cancer process remain unclear.METHOD: Stool samples from 52 patients with lung cancer and 29 healthy control individuals were collected and subjected to 16S rRNA gene amplification sequencing and non-targeted gas/liquid chromatography-mass spectrometry metabolomics analysis. Then microbiota, metabolites and potential signaling pathways that may play an important role in the disease were filtered.RESULTS: Firmicutes, Clostridia, Bacteroidacea, Bacteroides, and Lachnospira showed a greater abundance in healthy controls. In contrast, the Ruminococcus gnavus(R.gnavus) was significantly upregulated in lung cancer patients. In this respect, the micro-biome of the squamous cell carcinoma(SCC)group demonstrated a relatively higher abundance of Proteobacteria, Gammaproteobacteria, Bacteroides,and Enterobacteriaceae, as well as higher abundances of Fusicatenibacter and Roseburia in adenocarcinoma(ADC) group. Metabolomic analysis showed significant alterations in fecal metabolites including including quinic acid, 3-hydroxybenzoic acid,1-methylhydantoin,3,4-dihydroxydrocinnamic acid and 3,4-dihydroxybenzeneacetic acid were significantly altered in lung cancer patients. Additionally, the R.gnavus and Fusicatenibacter of lung cancer were associated with multiple metabolite levels.CONCLUSION: Our study provides essential guidance for a fundamental systematic and multilevel assessment of the contribution of gut micro-biome and their metabolites in lung cancer,which has great potential for understanding the pathogenesis of lung cancer and for better early prevention and targeted interventions.PMID:37577375 | PMC:PMC10415071 | DOI:10.3389/fcimb.2023.1170326

Effect of Benaglutide on Gut Microbiota and Fecal Metabolites in Patients with Type 2 Diabetes Mellitus

Mon, 14/08/2023 - 12:00
Diabetes Metab Syndr Obes. 2023 Aug 7;16:2329-2344. doi: 10.2147/DMSO.S418757. eCollection 2023.ABSTRACTOBJECTIVE: Benaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has been approved in the treatment of type 2 diabetes mellitus (T2DM). It is known to lead to significant weight loss, and it is hypothesized that changes in gut microbiota may play a significant role in such weight loss. However, it is unclear how gut microbiota and metabolites change as a result of benaglutide treatment.METHODS: Healthy participants and patients with T2DM were included in this study. They received differentiated treatments, and stool specimens were collected separately. These stool specimens were subjected to 16S ribosomal RNA amplicon and metagenomic sequencing to create fecal metabolomic profiles. The diversity of gut microbiota and metabolic products in the stools of each participant was analyzed.RESULTS: The data showed that Faecalibacterium prausnitzii was abundant in the gut microbiota of the control group, which was entirely made up of healthy individuals; however, it showed a statistically significant decrease in patients with T2DM treated with metformin alone, while no significant decrease was observed in patients treated with metformin combined with benaglutide. A metagenomic analysis revealed that benaglutide could improve the fecal microbiota diversity in patients with T2DM. Furthermore, there was a statistically significant correlation between the changes in the metabolites of patients with T2DM and the changes in their gut microbiota (including F. prausnitzii) after treatment with metformin and benaglutide.CONCLUSION: These findings suggest that the weight-reducing effect of benaglutide is attributed to its ability to normalize the gut microbiota of patients with T2DM, particularly by increasing the abundance of F. prausnitzii.PMID:37577040 | PMC:PMC10416789 | DOI:10.2147/DMSO.S418757

Conjoint analysis of transcriptome and metabolome profiles of normal captivity and arch soil free-range in Meishan pigs

Mon, 14/08/2023 - 12:00
Front Vet Sci. 2023 Jul 27;10:1187877. doi: 10.3389/fvets.2023.1187877. eCollection 2023.ABSTRACTThe hygiene hypothesis has been advanced as a potential explanation for the increasingly high levels of atopy and allergic disease in the general human population. In an effort to conduct a more detailed study of the link between immune activity and the hygiene hypothesis, Meishan pigs raised under normal captivity (NC) or arch soil free-range (ASF) conditions were selected as an experimental model system. Cytokine levels were found to differ significantly between these two groups consistent with a difference in cellular immune status. Integrated transcriptomic and metabolomic profiling of duodenal tissue samples from Meishan pigs were then performed, leading to the identification of differentially expressed genes (DEGs), differentially abundant metabolites (DAMs), and key pathways that were able to distinguish the NC and ASF groups. This approach led to the identification of 1,113 DEGs, as well as 577 and 372 DAMs in positive and negative ion modes, respectively. When an interaction network incorporating DEGs and metabolites associated with immune responsivity was constructed, it included factors such as 9-cis-Retinoic acid, (9Z,11E)-(13S)-13-Hydroxyoctadeca-9,11-dienoic acid and (10E,12Z)-(9S)-9-Hydroxyoctadeca-10,12-dienoic acid. Functional enrichment analyses confirmed that identified DEGs and DAMs were associated with immune-related pathways including the intestinal IgA production and PPAR signaling pathways. Together, these results offer new insight into the roles that particular genes and metabolites enriched in response to environmental stressors in free-range Meishan pigs may play in the regulation of cellular immunity, thus offering a foundation for future efforts to better understand the immunological mechanisms underlying the hygiene hypothesis.PMID:37576833 | PMC:PMC10421962 | DOI:10.3389/fvets.2023.1187877

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