PubMed

EBioMedicine. 2024 Mar 11;102:105056. doi: 10.1016/j.ebiom.2024.105056. Online ahead of print.ABSTRACTBACKGROUND: Chronic inflammatory diseases (CIDs) are systems disorders that affect diverse organs including the intestine, joints and skin. The essential amino acid tryptophan (Trp) can be broken down to various bioactive derivatives important for immune regulation. Increased Trp catabolism has been observed in some CIDs, so we aimed to characterise the specificity and extent of Trp degradation as a systems phenomenon across CIDs.METHODS: We used high performance liquid chromatography and targeted mass spectrometry to assess the serum and stool levels of Trp and Trp derivatives. Our retrospective study incorporates both cross-sectional and longitudinal components, as we have included a healthy population as a reference and there are also multiple observations per patient over time.FINDINGS: We found reduced serum Trp levels across the majority of CIDs, and a prevailing negative relationship between Trp and systemic inflammatory marker C-reactive protein (CRP). Notably, serum Trp was low in several CIDs even in the absence of measurable systemic inflammation. Increases in the kynurenine-to-Trp ratio (Kyn:Trp) suggest that these changes result from increased degradation along the kynurenine pathway.INTERPRETATION: Increases in Kyn:Trp indicate the kynurenine pathway as a major route for CID-related Trp metabolism disruption and the specificity of the network changes indicates excessive Trp degradation relative to other proteogenic amino acids. Our results suggest that increased Trp catabolism is a common metabolic occurrence in CIDs that may directly affect systemic immunity.FUNDING: This work was supported by the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation" (KA, SSchr, PR, BH, SWa), the BMBF (e:Med Juniorverbund "Try-IBD" 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), EKFS (2020_EKCS.11, KA), DFG RU5042 (PR, KA), and Innovative Medicines Initiative 2 Joint Undertakings ("Taxonomy, Treatments, Targets and Remission", 831434, "ImmUniverse", 853995, "BIOMAP", 821511).PMID:38471395 | DOI:10.1016/j.ebiom.2024.105056

J Hazard Mater. 2024 Mar 8;469:133985. doi: 10.1016/j.jhazmat.2024.133985. Online ahead of print.ABSTRACTIdentifying potent bacterial algicidal agents is essential for the development of effective, safe, and economically viable algaecides. Challenges in isolating and purifying these substances from complex secretions have impeded progress in this field. Metabolomics profiling, an efficient strategy for identifying metabolites, was pioneered in identifying bacterial algicidal substances in this study. Extracellular secretions from different generations of the algicidal bacterium Brevibacillus sp. were isolated for comprehensive analysis. Specifically, a higher algicidal efficacy was observed in the secretion from Generation 3 (G3) of Brevibacillus sp. compared to Generation 1 (G1). Subsequent metabolomics profiling comparing G3 and 1 revealed 83 significantly up-regulated metabolites, of which 9 were identified as potential algicidal candidates. Back-validation highlighted the potency of 4-acetamidobutanoic acid (4-ABC) and 8-hydroxyquinoline (8-HQL), which exhibited robust algicidal activity with 3d-EC50 values of 6.40 mg/L and 92.90 µg/L, respectively. These substances disrupted photosynthetic activity in M. aeruginosa by ceasing electron transfer in PSⅡ, like the impact exerted by Brevibacillus sp. secretion. These findings confirmed that 4-ABC and 8-HQL were the main algicidal components derived from Brevibacillus sp.. Thus, this study presents a streamlined strategy for identifying bacterial algicidal substances and unveils two novel and highly active algicidal substances. ENVIRONMENTAL IMPLICATION: Harmful cyanobacterial blooms (HCBs) pose significant environmental problems and health effects to humans and other organisms. The increasing frequency of HCBs has emerged as a pressing global concern. Bacterial-derived algicidal substances are expected to serve as effective, safe, and economically viable algaecides against HCBs. This study presents a streamlined strategy for identifying bacterial algicidal substances and unveils two novel substances (4-ABC and 8-HQL). These two substances demonstrate remarkable algicidal activity and disrupt the photosynthetic system in M. aeruginosa. They hold potential as prospective algaecides for addressing HCBs.PMID:38471378 | DOI:10.1016/j.jhazmat.2024.133985

Ecotoxicol Environ Saf. 2024 Mar 11;274:116183. doi: 10.1016/j.ecoenv.2024.116183. Online ahead of print.ABSTRACTArsenic is an environmentally ubiquitous toxic metalloid. Chronic exposure to arsenic may lead to arsenicosis, while no specific therapeutic strategies are available for the arsenism patients. And Ginkgo biloba extract (GBE) exhibited protective effect in our previous study. However, the mechanisms by which GBE protects the arsenism patients remain poorly understood. A liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics analysis was used to study metabolic response in arsenism patients upon GBE intervention. In total, 39 coal-burning type of arsenism patients and 50 healthy residents were enrolled from Guizhou province of China. The intervention group (n = 39) were arsenism patients orally administered with GBE (three times per day) for continuous 90 days. Plasma samples from 50 healthy controls (HC) and 39 arsenism patients before and after GBE intervention were collected and analyzed by established LC-MS method. Statistical analysis was performed by MetaboAnalyst 5.0 to identify differential metabolites. Multivariate analysis revealed a separation in arsenism patients between before (BG) and after GBE intervention (AG) group. It was observed that 35 differential metabolites were identified between BG and AG group, and 30 of them were completely or partially reversed by GBE intervention, with 14 differential metabolites significantly up-regulated and 16 differential metabolites considerably down-regulated. These metabolites were involved in promoting immune response and anti-inflammatory functions, and alleviating oxidative stress. Taken together, these findings indicate that the GBE intervention could probably exert its protective effects by reversing disordered metabolites modulating these functions in arsenism patients, and provide insights into further exploration of mechanistic studies.PMID:38471343 | DOI:10.1016/j.ecoenv.2024.116183

Phytomedicine. 2024 Feb 27;128:155495. doi: 10.1016/j.phymed.2024.155495. Online ahead of print.ABSTRACTBACKGROUND: Ginsenosides have received increased amounts of attention due to their ability to modulate the intestinal flora, which may subsequently alleviate alcoholic liver disease (ALD). The effects of ginseng fermentation solution (GFS) on the gut microbiota and metabolism in ALD patients have not been explored.PURPOSE: This research aimed to explore the regulatory effect of GFS on ALD both in vitro and in vivo.METHOD: This study assessed the anti-ALD efficacy of GFS using an LO2 cell model and a zebrafish model. Untargeted metabolomics was used for differentially abundant metabolite analysis, and high-throughput 16S rRNA sequencing was used to examine the effect of GFS on ALD.RESULTS: The LO2 cell line experiments demonstrated that GFS effectively mitigated alcohol-induced oxidative stress and reduced apoptosis by upregulating PI3K and Bcl-2 expression and decreasing the levels of malondialdehyde, total cholesterol, and triglycerides. In zebrafish, GFS improved morphological and physiological parameters and diminished oxidative stress-induced ALD. Meanwhile, the results from Western blotting indicated that GFS enhanced the expression of PI3K, Akt, and Bcl-2 proteins while reducing Bax protein expression, thereby ameliorating the ALD model in zebrafish. Metabolomics data revealed significant changes in a total of 46 potential biomarkers. Among them, metabolites such as prostaglandin F2 alpha belong to arachidonic acid metabolism. In addition, GFS also partly reversed the imbalance of gut microbiota composition caused by alcohol. At the genus level, alcohol consumption elevated the presence of Flectobacillus, Curvibacter, among others, and diminished Elizabethkingia within the intestinal microbes of zebrafish. Conversely, GFS reversed these effects, notably enhancing the abundance of Proteobacteria and Archaea. Correlation analyses further indicated a significant negative correlation between prostaglandin F2 alpha, 11,14,15-THETA, Taurocholic acid and Curvibacter.CONCLUSION: This study highlights a novel mechanism by which GFS modulates anti-ALD activity through the PI3K/Akt signalling pathway by influencing the intestinal flora-metabolite axis. These results indicate the potential of GFS as a functional food for ALD treatment via modulation of the gut flora.PMID:38471317 | DOI:10.1016/j.phymed.2024.155495

Anal Chem. 2024 Mar 12. doi: 10.1021/acs.analchem.3c05235. Online ahead of print.ABSTRACTMatrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which is a label-free imaging technique, determines the spatial distribution and relative abundance of versatile endogenous metabolites in tissues. Meanwhile, matrix selection is generally regarded as a pivotal step in MALDI tissue imaging. This study presents the first report of a novel MALDI matrix, 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine (HNTP), for the in situ detection and imaging of endogenous metabolites in rat liver and brain tissues by MALDI-MS in positive-ion mode. The HNTP matrix exhibits excellent characteristics, including strong ultraviolet absorption, μm-scale matrix crystals, high chemical stability, low background ion interference, and high metabolite ionization efficiency. Notably, the HNTP matrix also shows superior detection capabilities, successfully showing 185 detectable metabolites in rat liver tissue sections. This outperforms the commonly used matrices of 2,5-dihydroxybenzoic acid and 2-mercaptobenzothiazole, which detect 145 and 120 metabolites from the rat liver, respectively. Furthermore, a total of 152 metabolites are effectively detected and imaged in rat brain tissue using the HNTP matrix, and the spatial distribution of these compounds clearly shows the heterogeneity of the rat brain. The results demonstrate that HNTP is a new and powerful positive-ion mode matrix to enhance the analysis of metabolites in biological tissues by MALDI-MSI.PMID:38470972 | DOI:10.1021/acs.analchem.3c05235

Appl Environ Microbiol. 2024 Mar 12:e0179923. doi: 10.1128/aem.01799-23. Online ahead of print.ABSTRACTQueen and worker bees are natural models for aging research, as their lifespans vary considerably independent of genetic variation. Investigating the reasons why queens live longer than workers is of great significance for research on the universal processes of aging in animals. The gut microbiome has received attention as a vital regulator of host health, while its precise role in honeybee aging needs further investigation. The effects and mechanisms behind the relationship between gut microbiota and worker lifespan were measured by transplanting queen bee gut bacteria (QG) and worker bee gut bacteria (WG) into microbiota-free (MF) workers. The transplantation of QG to MF bees significantly extended the workers' lifespans compared with MF and WG bees. Untargeted metabolomics identified 49 lifespan-related differential metabolites, and Kyoto Encyclopedia of Genes and Genomes analysis of these revealed three lifespan-related metabolic pathways: insulin/insulin-like growth factor signaling, immune, and ketone body metabolism pathways. Further verification showed that QG inhibited the expression of insulin-like peptides (ILPs), and the expression of ILPs was lower in natural queens than in natural workers. QG transplantation also stimulated the expression of antioxidant genes and lowered oxidative damage products in natural queen bees. However, gut microbiota transplantation failed to mimic the immune properties and ketone body metabolism profiles of natural queens and workers. Concisely, QG could increase the antioxidant capacity to extend lifespan by inhibiting insulin signaling. These findings may help determine the mechanisms behind queen longevity and provide further insights into the role of gut symbionts.IMPORTANCE: Queen and worker bees share the same genetic background but have vastly different lifespans. The gut microbiome regulates host health, suggesting that differences in lifespan between queen and worker bees could be related to gut bacteria. Herein, we used an innovative method to transplant gut microbiota from adult queen or worker bees to microbiota-free bees. The transplantation of queen gut microbiota to microbiota-free bees extended their lifespan. Insulin/insulin-like growth factor signaling, a highly conserved metabolic pathway related to lifespan, displayed identical expression profiles in natural queen bees and microbiota-free bees transplanted with queen microbiota. This finding significantly expands our understanding of the relationships between intestinal bacteria, host health, and the biology of aging.PMID:38470148 | DOI:10.1128/aem.01799-23

mSystems. 2024 Mar 12:e0122523. doi: 10.1128/msystems.01225-23. Online ahead of print.ABSTRACTEctomycorrhizal fungi establish mutually beneficial relationships with trees, trading nutrients for carbon. Suillus are ectomycorrhizal fungi that are critical to the health of boreal and temperate forest ecosystems. Comparative genomics has identified a high number of non-ribosomal peptide synthetase and terpene biosynthetic gene clusters (BGC) potentially involved in fungal competition and communication. However, the functionality of these BGCs is not known. This study employed co-culture techniques to activate BGC expression and then used metabolomics to investigate the diversity of metabolic products produced by three Suillus species (Suillus hirtellus EM16, Suillus decipiens EM49, and Suillus cothurnatus VC1858), core members of the pine microbiome. After 28 days of growth on solid media, liquid chromatography-tandem mass spectrometry identified a diverse range of extracellular metabolites (exometabolites) along the interaction zone between Suillus co-cultures. Prenol lipids were among the most abundant chemical classes. Out of the 62 unique terpene BGCs predicted by genome mining, 41 putative prenol lipids (includes 37 putative terpenes) were identified across the three Suillus species using metabolomics. Notably, some terpenes were significantly more abundant in co-culture conditions. For example, we identified a metabolite matching to isomers isopimaric acid, sandaracopimaric acid, and abietic acid, which can be found in pine resin and play important roles in host defense mechanisms and Suillus spore germination. This research highlights the importance of combining genomics and metabolomics to advance our understanding of the chemical diversity underpinning fungal signaling and communication.IMPORTANCEUsing a combination of genomics and metabolomics, this study's findings offer new insights into the chemical diversity of Suillus fungi, which serve a critical role in forest ecosystems.PMID:38470040 | DOI:10.1128/msystems.01225-23

mSystems. 2024 Mar 12:e0006424. doi: 10.1128/msystems.00064-24. Online ahead of print.ABSTRACTDuring prolonged resource limitation, bacterial cells can persist in metabolically active states of non-growth. These maintenance periods, such as those experienced in stationary phase, can include upregulation of secondary metabolism and release of exometabolites into the local environment. As resource limitation is common in many environmental microbial habitats, we hypothesized that neighboring bacterial populations employ exometabolites to compete or cooperate during maintenance and that these exometabolite-facilitated interactions can drive community outcomes. Here, we evaluated the consequences of exometabolite interactions over the stationary phase among three environmental strains: Burkholderia thailandensis E264, Chromobacterium subtsugae ATCC 31532, and Pseudomonas syringae pv. tomato DC3000. We assembled them into synthetic communities that only permitted chemical interactions. We compared the responses (transcripts) and outputs (exometabolites) of each member with and without neighbors. We found that transcriptional dynamics were changed with different neighbors and that some of these changes were coordinated between members. The dominant competitor B. thailandensis consistently upregulated biosynthetic gene clusters to produce bioactive exometabolites for both exploitative and interference competition. These results demonstrate that competition strategies during maintenance can contribute to community-level outcomes. It also suggests that the traditional concept of defining competitiveness by growth outcomes may be narrow and that maintenance competition could be an additional or alternative measure.IMPORTANCE: Free-living microbial populations often persist and engage in environments that offer few or inconsistently available resources. Thus, it is important to investigate microbial interactions in this common and ecologically relevant condition of non-growth. This work investigates the consequences of resource limitation for community metabolic output and for population interactions in simple synthetic bacterial communities. Despite non-growth, we observed active, exometabolite-mediated competition among the bacterial populations. Many of these interactions and produced exometabolites were dependent on the community composition but we also observed that one dominant competitor consistently produced interfering exometabolites regardless. These results are important for predicting and understanding microbial interactions in resource-limited environments.PMID:38470039 | DOI:10.1128/msystems.00064-24

Adv Healthc Mater. 2024 Mar 12:e2303995. doi: 10.1002/adhm.202303995. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) causes inflammatory and metabolic imbalances in tissue, which then exacerbates inflammation in affected joints. Therefore, restoring tissue homeostasis is necessary for the remission of RA symptoms. In fact, the changes in immunological and metabolic tissue homeostasis at different stages of the disease is not well understood. Herein, the changes in the immunological metabolic profiles in different stages of RA namely, early, intermediate, and late stage was examined. Moreover, the efficacy of the microparticle inverse-vaccine, paKG(PFK15+bc2) to restore immunological and metabolic tissue homeostasis at different stages of the disease was also investigated. Analysis of the immune cell profiles revealed that there was a significant decrease in the activation of pro-inflammatory immune cells while a remarkable increase was seen in regulatory T-cell populations in the intermediate and late stages of RA in the inverse-vaccine treated group as compared to no treatment. Also, it was determined that glycolysis in the spleen was normalized in the late stages of CIA, which was similar to no disease tissues. Using metabolomics we identified, key metabolites UDP-glucuronic acid and L-Glutathione oxidized that were significantly altered between treatment groups, and thus might provide new druggable targets for RA. We also employed flux metabolic modeling of the metabolomics data to identify amino acid and carnitine pathways as the central pathways affected at the tissue-level in CIA as the disease progresses. Overall, this study shows that the inverse-vaccines initiate early re-establishment of homeostasis and persists through the disease span. This article is protected by copyright. All rights reserved.PMID:38469995 | DOI:10.1002/adhm.202303995

Am J Physiol Lung Cell Mol Physiol. 2024 Mar 12. doi: 10.1152/ajplung.00266.2023. Online ahead of print.ABSTRACTAcute respiratory distress syndrome (ARDS) is a fatal pulmonary disorder characterized by severe hypoxia and inflammation. Systemic and pulmonary infections are a leading cause of ARDS. The common respiratory pathogens include bacteria and virus, including Pseudomonas aeruginosa, Streptococcus aureus, Enterobacter species, coronavirus, influenza, and herpesviruses. COVID-19-associated ARDS is a new etiologic phenotype of the disease. The pathogenesis of ARDS caused by bacteria and viruses differs in host immune responses and lung mesenchymal injury. We postulate that both systemic and lung metabolomics of ARDS induced by virus may differ from those infected by other pathogens. This review aims to compare the metabolic signatures in blood and lung specimens. Both common and SARS-CoV-2-specific metabolomic signatures were comprehensively reviewed. The differences in metabolic profiles between COVID-19 and other etiology-associated ARDS may uncover new biomarkers, pathogenic mechanisms, druggable targets, and differential diagnosis.PMID:38469648 | DOI:10.1152/ajplung.00266.2023

Front Gastroenterol (Lausanne). 2023;2:1087056. doi: 10.3389/fgstr.2023.1087056. Epub 2023 Feb 15.ABSTRACTINTRODUCTION: Dietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.METHODS: Adults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol®-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure via 16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.RESULTS: Across biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure.DISCUSSION: Dietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.PMID:38469373 | PMC:PMC10927265 | DOI:10.3389/fgstr.2023.1087056

Front Immunol. 2024 Feb 26;15:1347871. doi: 10.3389/fimmu.2024.1347871. eCollection 2024.ABSTRACTThe antibody- FcγRIIIa interaction triggers key immunological responses such as antibody dependent cellular cytotoxicity (ADCC), making it highly important for therapeutic mAbs. Due to the direct glycan-glycan interaction with FcγRIIIa receptor, differences in antibody glycosylation can drastically influence the binding affinity. Understanding the differential binding of mAb glycoforms is a very important, yet challenging task due to the co-existence of multiple glycoforms in a sample. Affinity liquid chromatography (AC) and affinity capillary electrophoresis (ACE) hyphenated with mass spectrometry (MS) can provide glycoform-resolved affinity profiles of proteins based on their differences in either dissociation (AC) or equilibrium (ACE) constants. To cross-validate the affinity ranking provided by these complementary novel approaches, both techniques were benchmarked using the same FcγRIIIa constructs. Both approaches were able to assess the mAb - FcγRIIIa interaction in a glycoform selective manner and showed a clear increase in binding for fully versus hemi-fucosylated mAbs. Also, other features, such as increasing affinity with elevated galactosylation or the binding affinity for high mannose glycoforms were consistent. We further applied these approaches to assess the binding towards the F158 allotype of FcγRIIIa, which was not reported before. The FcγRIIIa F158 allotype showed a very similar profile compared to the V158 receptor with the strongest increase in binding due to afucosylation and only a slight increase in binding with additional galactosylation. Both techniques showed a decrease of the binding affinity for high mannose glycoforms for FcγRIIIa F158 compared to the V158 variant. Overall, both approaches provided very comparable results in line with orthogonal methods proving the capabilities of separation-based affinity approaches to study FcγR binding of antibody glycoforms.PMID:38469305 | PMC:PMC10925690 | DOI:10.3389/fimmu.2024.1347871

Health Sci Rep. 2024 Mar 10;7(3):e1895. doi: 10.1002/hsr2.1895. eCollection 2024 Mar.ABSTRACTBACKGROUND AND AIMS: The aim is to investigate the cause-and-effect connection between metabolites found in blood/urine and the likelihood of developing periodontal disease (PD) through the utilization of a two-sample Mendelian randomization (MR) method.METHODS: Using an inverse variance weighted (IVW) method and two additional two-sample MR models, we examined the relationship between blood/urine metabolites and PD by analyzing data from a comprehensive metabolome-based genome-wide association study and the Genome-Wide Association Studies (GWAS) of PD. To assess the consistency and dependability of the findings, diversity, cross-effects, and sensitivity analyses were conducted.RESULTS: Out of the 35 metabolites found in blood and urine, a total of eight metabolites (C-reactive protein, Potassium in urine, Urea, Cystatin C, Non-albumin protein, Creatinine, estimated Glomerular Filtration Rate, and Phosphate) displayed a possible causal connection with the risk of dental caries/PD using the inverse variance weighted (IVW) method (p < 0.05). This includes five metabolites in the blood and three in the urine. No metabolites were statistically significant in IVW MR models (p < 3.68 × 10- 4). Even after conducting sensitivity analysis with the leave-one-out method and removing the confounding instrumental variables, the impact of these factors on dental caries/PD remained significant.CONCLUSION: Based on the available evidence, it is not possible to establish a significant causal link between the 35 blood metabolites and the likelihood of developing dental caries and PD.PMID:38469110 | PMC:PMC10925816 | DOI:10.1002/hsr2.1895

Sleep Biol Rhythms. 2023 Feb 8;21(3):265-277. doi: 10.1007/s41105-023-00445-5. eCollection 2023 Jul.ABSTRACTObstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression.PMID:38469078 | PMC:PMC10899929 | DOI:10.1007/s41105-023-00445-5

Front Microbiol. 2024 Feb 26;15:1268813. doi: 10.3389/fmicb.2024.1268813. eCollection 2024.ABSTRACTBacterial outer membrane vesicles (OMVs) contain a variety of chemical compounds and play significant roles in maintaining symbiotic relationships in a changing ocean, but little is known about their function, particularly in sponge larval development. During the growth of sponge Tedania sp., OMVs from Bacteroidetes species significantly promoted larval settlement, and Tenacibaculum mesophilum SP-7-OMVs were selected as a representative strain for further investigation. According to OMVs metabolomics, larval settlement might be connected to organic acids and derivatives. The multiomics analysis of the T. mesophilum genome, SP-7-OMVs metabolome, and larval transcriptome revealed 47 shared KEGG pathways. Among the number of candidate metabolites, arginine was chosen for its greater ability to increase the settlement rate and its role as the principal substrate for nitric oxide (NO) synthesis of sponge larvae. In summary, these results demonstrated that sponge-associated bacteria might utilize OMVs and their cargo to support host development and make up for host metabolic pathway deficiencies. This study enhances our fundamental knowledge of OMVs in interactions between metazoan hosts and microorganisms that are crucial in the coevolution of marine ecosystems and the complex marine environment.PMID:38468855 | PMC:PMC10925772 | DOI:10.3389/fmicb.2024.1268813

Food Chem X. 2024 Mar 1;22:101265. doi: 10.1016/j.fochx.2024.101265. eCollection 2024 Jun 30.ABSTRACTAdulteration in dairy products presents food safety challenges, driven by economic factors. Processing may change specific biomarkers, thus affecting their effectiveness in detection. In this study, proteomics and metabolomics approaches were to investigate the detection of bovine milk (BM) constituents adulteration in pasteurized mare milk (PMM) and mare milk powder (MMP). Several bovine proteins and metabolites were identified, with their abundances in PMM and MMP increasing upon addition of BM. Proteins like osteopontin (OPN) and serotransferrin (TF) detected adulteration down to 1 % in PMM, whereas these proteins in MMP were utilized to identify 10 % adulteration. Biotin and N6-Me-adenosine were effective in detecting adulteration in PMM as low as 10 % and 1 % respectively, while in MMP, their detection limits extend down to 0.1 %. These findings offer insights for authenticating mare milk products and underscore the influence of processing methods on biomarker levels, stressing the need to consider these effects in milk product authentication.PMID:38468636 | PMC:PMC10926301 | DOI:10.1016/j.fochx.2024.101265

Food Chem X. 2024 Mar 1;22:101264. doi: 10.1016/j.fochx.2024.101264. eCollection 2024 Jun 30.ABSTRACTWorkshop with different fermentation years plays an essential role in the yield and quality of Baijiu. In actual production, the quality of base Baijiu in newly built workshop is inferior to the older one. In this study, the microbiota of workshop environment and fermentation process from two workshops namely N (ferment 2 years) and O (ferment 20 years) and flavor compounds were studied during Xiasha round. Results showed workshop O accumulated more environmental microorganisms and fungi including P. kudriavzevii, Wickerhamomyces anomalus and Saccharomyces sp mainly came from ground. Yeasts including Pichia, Cyberlindnera, Wickerhamomyces and Candida were responsible for flavor substances formation in O while Saccharopolyspora was in N. This study for the first time explored the reasons for the brewing differences among N and O workshop from perspectives of workshop environment, microbial community and flavor substances, providing new ideas for guiding production as well as improvement of Baijiu quality.PMID:38468635 | PMC:PMC10926306 | DOI:10.1016/j.fochx.2024.101264

Clin Transl Med. 2024 Mar;14(3):e1624. doi: 10.1002/ctm2.1624.NO ABSTRACTPMID:38468504 | DOI:10.1002/ctm2.1624

Eur J Heart Fail. 2024 Mar 11. doi: 10.1002/ejhf.3192. Online ahead of print.ABSTRACTAIMS: Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF.METHODS AND RESULTS: Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment.CONCLUSIONS: Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.PMID:38468429 | DOI:10.1002/ejhf.3192

Genome Biol. 2024 Mar 11;25(1):66. doi: 10.1186/s13059-024-03208-8.ABSTRACTBACKGROUND: Oncometabolites, often generated as a result of a gene mutation, show pro-oncogenic function when abnormally accumulated in cancer cells. Identification of such mutation-associated metabolites will facilitate developing treatment strategies for cancers, but is challenging due to the large number of metabolites in a cell and the presence of multiple genes associated with cancer development.RESULTS: Here we report the development of a computational workflow that predicts metabolite-gene-pathway sets. Metabolite-gene-pathway sets present metabolites and metabolic pathways significantly associated with specific somatic mutations in cancers. The computational workflow uses both cancer patient-specific genome-scale metabolic models (GEMs) and mutation data to generate metabolite-gene-pathway sets. A GEM is a computational model that predicts reaction fluxes at a genome scale and can be constructed in a cell-specific manner by using omics data. The computational workflow is first validated by comparing the resulting metabolite-gene pairs with multi-omics data (i.e., mutation data, RNA-seq data, and metabolome data) from acute myeloid leukemia and renal cell carcinoma samples collected in this study. The computational workflow is further validated by evaluating the metabolite-gene-pathway sets predicted for 18 cancer types, by using RNA-seq data publicly available, in comparison with the reported studies. Therapeutic potential of the resulting metabolite-gene-pathway sets is also discussed.CONCLUSIONS: Validation of the metabolite-gene-pathway set-predicting computational workflow indicates that a decent number of metabolites and metabolic pathways appear to be significantly associated with specific somatic mutations. The computational workflow and the resulting metabolite-gene-pathway sets will help identify novel oncometabolites and also suggest cancer treatment strategies.PMID:38468344 | DOI:10.1186/s13059-024-03208-8