PubMed

Proteomics. 2023 Jul 25:e2200325. doi: 10.1002/pmic.202200325. Online ahead of print.ABSTRACTThe retinal pigment epithelial (RPE)/choroid complex regulates myopia development, but the precise pathogenesis of myopia remains unclear. We aimed to investigate the changes in RPE/choroid complex metabolism in a form deprivation myopia model after dopamine D2 receptor (D2R) modulation. Guinea pigs were randomly divided into normal (NC), form deprivation myopia (FDM), and FDM treated with dopamine D2R antagonist groups. Differential metabolites were screened using SIMCA-P software and MetaboAnalyst metabolomics analysis tool. Functions of differential metabolites were analyzed using KEGG enrichment pathways. Relative to the NC group, 38 differential metabolites were identified, comprising 29 increased metabolites (including nicotinic acid, cytosine, and glutamate) and 9 decreased metabolites, of which proline exhibited the largest decrease. Pathway analysis revealed regulation of arginine/proline and aspartate/glutamate metabolism. Intravitreal D2R antagonist injection increased proline concentrations and activated arginine/proline and purine metabolism pathways. In sum, D2R antagonists alleviated the myopia trend of refractive biological parameters in form deprivation myopic guinea pigs, suggesting the involvement of dopamine D2R signaling in myopia pathogenesis. The RPE/choroid may provide glutamate to the retina by activating proline metabolism via metabolic coupling with the retina. Dopamine D2R antagonism may modulate proline/arginine metabolic pathways in the RPE/choroid and regulate metabolism, information presentation, and myopia.PMID:37491763 | DOI:10.1002/pmic.202200325

JCO Clin Cancer Inform. 2023 Jul;7:e2300057. doi: 10.1200/CCI.23.00057.ABSTRACTPURPOSE: To determine prognostic and predictive clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) on the basis of a combination of plasma-derived genomic alterations and lipid features in a longitudinal cohort of patients with advanced prostate cancer.METHODS: A multifeature classifier was constructed to predict clinical outcomes using plasma-based genomic alterations detected in 120 genes and 772 lipidomic species as informative features in a cohort of 71 patients with mHSPC and 144 patients with mCRPC. Outcomes of interest were collected over 11 years of follow-up. These included in mHSPC state early failure of androgen-deprivation therapy (ADT) and exceptional responders to ADT; early death (poor prognosis) and long-term survivors in mCRPC state. The approach was to build binary classification models that identified discriminative candidates with optimal weights to predict outcomes. To achieve this, we built multi-omic feature-based classifiers using traditional machine learning (ML) methods, including logistic regression with sparse regularization, multi-kernel Gaussian process regression, and support vector machines.RESULTS: The levels of specific ceramides (d18:1/14:0 and d18:1/17:0), and the presence of CHEK2 mutations, AR amplification, and RB1 deletion were identified as the most crucial factors associated with clinical outcomes. Using ML models, the optimal multi-omics feature combination determined resulted in AUC scores of 0.751 for predicting mHSPC survival and 0.638 for predicting ADT failure; and in mCRPC state, 0.687 for prognostication and 0.727 for exceptional survival. The models were observed to be superior than using a limited candidate number of features for developing multi-omic prognostic and predictive signatures.CONCLUSION: Using a ML approach that incorporates multiple omic features improves the prediction accuracy for metastatic prostate cancer outcomes significantly. Validation of these models will be needed in independent data sets in future.PMID:37490642 | DOI:10.1200/CCI.23.00057

Microbiome. 2023 Jul 25;11(1):159. doi: 10.1186/s40168-023-01594-y.ABSTRACTBACKGROUND: Cervicovaginal inflammation has been linked to negative reproductive health outcomes including the acquisition of HIV, other sexually transmitted infections, and cervical carcinogenesis. While changes to the vaginal microbiome have been linked to genital inflammation, the molecular relationships between the functional components of the microbiome with cervical immunology in the reproductive tract are understudied, limiting our understanding of mucosal biology that may be important for reproductive health.RESULTS: In this study, we used a multi'-omics approach to profile cervicovaginal samples collected from 43 Canadian women to characterize host, immune, functional microbiome, and metabolome features of cervicovaginal inflammation. We demonstrate that inflammation is associated with lower amounts of L. crispatus and higher levels of cervical antigen-presenting cells (APCs). Proteomic analysis showed an upregulation of pathways related to neutrophil degranulation, complement, and leukocyte migration, with lower levels of cornified envelope and cell-cell adherens junctions. Functional microbiome analysis showed reductions in carbohydrate metabolism and lactic acid, with increases in xanthine and other metabolites. Bayesian network analysis linked L. crispatus with glycolytic and nucleotide metabolism, succinate and xanthine, and epithelial proteins SCEL and IVL as major molecular features associated with pro-inflammatory cytokines and increased APCs.CONCLUSIONS: This study identified key molecular and immunological relationships with cervicovaginal inflammation, including higher APCs, bacterial metabolism, and proteome alterations that underlie inflammation. As APCs are involved in HIV transmission, parturition, and cervical cancer progression, further studies are needed to explore the interactions between these cells, bacterial metabolism, mucosal immunity, and their relationship to reproductive health. Video Abstract.PMID:37491398 | DOI:10.1186/s40168-023-01594-y

J Transl Med. 2023 Jul 25;21(1):498. doi: 10.1186/s12967-023-04214-3.ABSTRACTBACKGROUND: Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota.METHODS: We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin.RESULTS: We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages.CONCLUSION: Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD.PMID:37491256 | DOI:10.1186/s12967-023-04214-3

Gut. 2023 Jul 25:gutjnl-2023-330291. doi: 10.1136/gutjnl-2023-330291. Online ahead of print.ABSTRACTOBJECTIVE: Roseburia intestinalis is a probiotic species that can suppress intestinal inflammation by producing metabolites. We aimed to study the role of R. intestinalis in colorectal tumourigenesis and immunotherapy.DESIGN: R. intestinalis abundance was evaluated in stools of patients with colorectal cancer (CRC) (n=444) and healthy controls (n=575). The effects of R. intestinalis were studied in ApcMin/+ or azoxymethane (AOM)-induced CRC mouse models, and in syngeneic mouse xenograft models of CT26 (microsatellite instability (MSI)-low) or MC38 (MSI-high). The change of immune landscape was evaluated by multicolour flow cytometry and immunohistochemistry staining. Metabolites were profiled by metabolomic profiling.RESULTS: R. intestinalis was significantly depleted in stools of patients with CRC compared with healthy controls. R. intestinalis administration significantly inhibited tumour formation in ApcMin/+ mice, which was confirmed in mice with AOM-induced CRC. R. intestinalis restored gut barrier function as indicated by improved intestinal permeability and enhanced expression of tight junction proteins. Butyrate was identified as the functional metabolite generated by R. intestinalis. R. intestinalis or butyrate suppressed tumour growth by inducing cytotoxic granzyme B+, interferon (IFN)-γ+ and tumour necrosis factor (TNF)-α+ CD8+ T cells in orthotopic mouse models of MC38 or CT26. R. intestinalis or butyrate also significantly improved antiprogrammed cell death protein 1 (anti-PD-1) efficacy in mice bearing MSI-low CT26 tumours. Mechanistically, butyrate directly bound to toll-like receptor 5 (TLR5) receptor on CD8+ T cells to induce its activity through activating nuclear factor kappa B (NF-κB) signalling.CONCLUSION: R. intestinalis protects against colorectal tumourigenesis by producing butyrate, which could also improve anti-PD-1 efficacy by inducing functional CD8+ T cells. R. intestinalis is a potential adjuvant to augment anti-PD-1 efficacy against CRC.PMID:37491158 | DOI:10.1136/gutjnl-2023-330291

J Agric Food Chem. 2023 Jul 25. doi: 10.1021/acs.jafc.3c00043. Online ahead of print.ABSTRACTHeat stress (HS) negatively influences cows' welfare and productivity. Therefore, a better understanding of the physiological and molecular mechanisms of HS responses from multiple parities is paramount for the development of effective management and breeding strategies. In comparison with first-parity cows in the spring (Spring-1), first-parity cows in the summer (Summer-1) had a significantly higher rectal temperature (RT), respiration rate (RR), drooling score (DS), and daily activity (DA), while lower (P < 0.05) daily rumination (DR), seven-day average milk yield (7AMY), milk yield on sampling day (MY_S), milk yield on test day (MY_T), and lactose percentage (LP) were observed. When comparing the spring (Spring-2) and summer (Summer-2) of the second-parity cows, significant differences were also found in RT, RR, DS, DA, and DR (P < 0.05), corresponding to similar trends with the first parity while having smaller changes. Moreover, significantly negative impacts on performance traits were only observed on fat percentage (FP) and LP. These results showed that there were different biological responses between first- and second-parity Holstein cows. Further, 18 and 17 metabolites were involved in the seasonal response of first- and second-parity cows, respectively. Nine differential metabolites were shared between the two parities, and pathway analyses suggested that cows had an inhibited tricarboxylic acid cycle, increased utilization of lipolysis, and a dysregulated gut microbiome during the summer. The metabolites identified exclusively for each parity highlighted the differences in microbial response and host amino acid metabolism between two parities in response to HS. Moreover, glucose, ethanol, and citrate were identified as potential biomarkers for distinguishing individuals between Spring-1 and Summer-1. Ethanol and acetone were better predictors for distinguishing individuals between Spring-2 and Summer-2. Taken together, the present study demonstrated the impact of naturally induced HS on physiological parameters, production traits, and the blood metabolome of Holstein cows. There are different biological responses and regulation mechanisms between first- and second-parity Holstein cows.PMID:37490609 | DOI:10.1021/acs.jafc.3c00043

J Nat Prod. 2023 Jul 25. doi: 10.1021/acs.jnatprod.3c00383. Online ahead of print.ABSTRACTMetabolomics analyses and improvement of growth conditions were applied toward diversification of phomactin terpenoids by the fungus Biatriospora sp. CBMAI 1333. Visualization of molecular networking results on Gephi assisted the observation of phomactin diversification and guided the isolation of new phomactin variants by applying a modified version of chemometrics based on a fractional factorial design. Consequentially, the first nitrogen-bearing phomactin, phomactinine (1), with a new rearranged carbon skeleton, was isolated and identified. The strategy combining metabolomics and chemometrics can be extended to include bioassay potency, structure novelty, and metabolic diversification connected or not to genomic analyses.PMID:37490470 | DOI:10.1021/acs.jnatprod.3c00383

Bioinformatics. 2023 Jul 25:btad455. doi: 10.1093/bioinformatics/btad455. Online ahead of print.ABSTRACTSUMMARY: The Integrated Probabilistic Annotation (IPA) is an automated annotation method for LC-MS-based untargeted metabolomics experiments, that provides statistically rigorous estimates of the probabilities associated with each annotation. Here we introduce ipaPy2, a substantially improved and completely refactored Python implementation of the IPA method. The revised method is now able to integrate tandem MS fragmentation data, which increases the accuracy of the identifications. Moreover, ipaPy2 provides a much more user-friendly interface, and isotope peaks are no longer treated as individual features, but integrated into isotope fingerprints, greatly speeding up the calculations. The method has also been fully integrated with the mzMatch pipeline, so that the results of the annotation can be explored through the newly developed PeakMLViewerPy tool available at https://github.com/UoMMIB/PeakMLViewerPy.AVAILABILITY AND IMPLEMENTATION: The source code, extensive documentation and tutorials are freely available on GitHub at https://github.com/francescodc87/ipaPy2.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:37490466 | DOI:10.1093/bioinformatics/btad455

Chem Commun (Camb). 2023 Jul 25. doi: 10.1039/d3cc01861j. Online ahead of print.ABSTRACTPrecision diagnosis and classification of autoimmune diseases (ADs) is challenging due to the obscure symptoms and pathological causes. Biofluid metabolic analysis has the potential for disease screening, in which high throughput, rapid analysis and minimum sample consumption must be addressed. Herein, we performed metabolomic profiling by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in urine and serum samples. Combined with machine learning (ML), metabolomic patterns from urine achieved the discrimination and classification of ADs with high accuracy. Furthermore, metabolic disturbances among different ADs were also investigated, and provided information of etiology. These results demonstrated that urine metabolic patterns based on MALDI-MS and ML manifest substantial potential in precision medicine.PMID:37490058 | DOI:10.1039/d3cc01861j

J Breath Res. 2023 Jul 25. doi: 10.1088/1752-7163/acea3d. Online ahead of print.ABSTRACTInfection of airway epithelial cells with severe acute respiratory coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and lung injury with hypoxia. It is challenging to sample the lower airways non-invasively and the capability to identify a highly representative specimen that can be collected in a non-invasive way would provide opportunities to investigate metabolomic consequences of COVID-19 disease. In the present study, we performed a targeted metabolomic approach using liquid chromatography coupled with high resolution chromatography (LC-MS) on exhaled breath condensate (EBC) collected from hospitalized COVID-19 patients (COVID+) and negative controls, both non-hospitalized and hospitalized for other reasons (COVID-). We were able to noninvasively identify and quantify inflammatory oxylipin shifts and dysregulation that may ultimately be used to monitor COVID-19 disease progression or severity and response to therapy. &#xD;The results indicate ten targeted oxylipins with significant differences between SAR-CoV-2 infected EBC samples and negative control samples. These compounds were prostaglandins A2 and D2, LXA4, 5-HETE, 12-HETE, 15-HETE, 5-HEPE, 9-HODE, 13-oxoODE and 19(20)-EpDPA, which are associated with specific pathways (i.e. P450, COX, 15-LOX) related to inflammatory and oxidative stress processes. Moreover, all these compounds were up-regulated in the COVID+ group, meaning their concentrations were higher in subjects with SAR-CoV-2 infection. Given that many COVID symptoms are inflammatory in nature, this is interesting insight into the pathophysiology of the disease. Breath monitoring of these and other EBC metabolites presents an interesting opportunity to monitor key indicators of disease progression and severity.&#xD.PMID:37489864 | DOI:10.1088/1752-7163/acea3d

Plant Cell Physiol. 2023 Jul 4:pcad071. doi: 10.1093/pcp/pcad071. Online ahead of print.ABSTRACTPlants incorporate acquired carbon and nitrogen into amino acid metabolism, whereby the building blocks of proteins and the precursors of various metabolites are produced. This fundamental demand requires tight amino acid metabolism to sustain physiological homeostasis. There is increasing evidence that amino acid metabolism undergoes plastic alteration to orchestrate specific growth and developmental events. Consequently, there has been a gradual exploration of the interface at which amino acid metabolism and plant morphogenesis are mutually affected. This research progress offers an opportunity to explore amino acid metabolism, with the goal to understand how it can be modulated to serve special cellular needs and regulate specific growth and developmental pathways. Continuous improvements in the sensitivity and coverage of metabolomics technology, along with the development of chemoinformatics, have allowed the investigation of these research questions. In this review, we summarize the roles of threonine, serine, arginine and γ-aminobutyric acid as representative examples of amino acids relevant to specific developmental processes in plants ('functional amino acids'). Our objective is to expand perspectives regarding amino acid metabolism beyond the conventional view that it is merely life-supporting machinery.PMID:37489637 | DOI:10.1093/pcp/pcad071

Diseases. 2023 Jul 5;11(3):94. doi: 10.3390/diseases11030094.ABSTRACTPlasmodium falciparum (P. falciparum) and hepatitis B virus (HBV) co-infection is on the rise among pregnant women in northern Ghana. Mono-infection with either of these two pathogens results in unique metabolic alterations. Thus, we aimed to explicate the effects of this co-infection on the metabolome signatures of pregnant women, which would indicate the impacted metabolic pathways and provide useful prognostic or diagnostic markers. Using an MS/MS-based targeted metabolomic approach, we determined the serum metabolome in pregnant women with P. falciparum mono-infection, HBV mono-infection, P. falciparum, and HBV co-infection and in uninfected (control) women. We observed significantly decreased sphingolipid concentrations in subjects with P. falciparum mono-infection, whereas amino acids and phospholipids were decreased in subjects with HBV mono-infection. Co-infections were found to be characterized distinctively by reduced concentrations of phospholipids and hexoses (mostly glucose) as well as altered pathways that contribute to redox homeostasis. Overall, PC ae C40:1 was found to be a good discriminatory metabolite for the co-infection group. PC ae C40:1 can further be explored for use in the diagnosis and treatment of malaria and chronic hepatitis B co-morbidity as well as to distinguish co-infections from cases of mono-infections.PMID:37489446 | DOI:10.3390/diseases11030094

Neurol Int. 2023 Jul 23;15(3):881-895. doi: 10.3390/neurolint15030056.ABSTRACTBACKGROUND: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of knowledge regarding known COVID-19 in critical patients. We searched PubMed® using the Boolean operators and identified all results on the PubMed® database of all studies regarding COVID-19 biomarkers. We selected studies regarding endothelium, cytokines, bacterial infection, coagulation, and cardiovascular biomarkers.METHODS: We divided the results into four essential paragraphs: "Cytokine storm", "Endothelium dysfunction and coagulation biomarkers in COVID-19", "Biomarker of sepsis", and Cardiovascular lung and new perspectives.RESULTS: The assessments of the severe COVID-19 prognosis should monitor, over time, IL-6, soluble Von Willebrand factor (VWF), P-selectin, sCD40L, thrombomodulin, VCAM-1, endothelin- Troponin, D-dimer, LDH, CRP, and procalcitonin. Metabolomic alterations and ACE2 receptors represent new perspectives.DISCUSSION AND CONCLUSIONS: Early identification of critically ill patients has been crucial in the first COVID-19 pandemic wave for the sustainability of the healthcare emergency system and clinical management. Only through the early identification of the most severe patients can they be provided with the most appropriate treatments.PMID:37489362 | DOI:10.3390/neurolint15030056

Int J Nanomedicine. 2023 Jul 19;18:3951-3972. doi: 10.2147/IJN.S410996. eCollection 2023.ABSTRACTINTRODUCTION: Drug-resistant bacterial infections and biofilm formation play important roles in the pathogenesis of diabetic refractory wounds. Tea tree oil (TTO) exhibits antimicrobial, antimycotic, and antiviral activities, especially against common clinically resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making it a potential natural antimicrobial for the treatment of acute and chronic wounds. However, TTO is insoluble in water, volatile, light-sensitive, and cytotoxic. While previous macroscopic studies have focused on sterilization with TTO, none have sought to alter its structure or combine it with other materials to achieve sustained release.METHODS: Electrospun TTO nanoliposomes (TTO-NLs), arranged linearly via high-pressure homogenization, could stabilize the structure and performance of TTO to achieve slow drug release. Herein, we established a composite nano-sustained release system, TTO-NL/polyvinyl alcohol/chitosan (TTO-NL@PCS), using high-voltage electrospinning.RESULTS: Compared with the control, TTO-NL@PCS exhibits higher concentrations of the active TTO drug components, terpinen-4-ol and 1,8-cineole. Owing to its increased stability and slow release, early exposure to TTO-NL@PCS increases the abundance of reactive oxygen species in vitro, ultimately causing the biofilm to disperse and completely killing MRSA without inducing cytotoxic effects to the host. Moreover, in BKS-Leprem2Cd479/Gpt mice with a whole-layer skin infection, untargeted metabolomics analysis of wound exudates reveals upregulated PGF2α/FP receptor signaling and interleukin (IL)-1β and IL-6 expression following application of the composite system. The composite also ameliorates the chemotaxis disorder in early treatment and attenuates the wound inflammatory response during the repair stage of diabetic inflammatory wounds, and upregulates VEGF expression in the wound bed.CONCLUSION: TTO-NL@PCS demonstrates the remarkable potential for accelerating diabetic and MRSA-infected wound healing.PMID:37489140 | PMC:PMC10363391 | DOI:10.2147/IJN.S410996

ACS Appl Mater Interfaces. 2023 Jul 24. doi: 10.1021/acsami.3c07598. Online ahead of print.ABSTRACTSpodoptera frugiperda (S. frugiperda) is an invasive pest that threatens global crop production and food security and poses a serious threat to maize production worldwide. Metal-organic framework (MOF) nanocarriers have great potential for agricultural pest control applications. The present study successfully prepared the chemical cross-linking of iron-based metal-organic framework nanoparticles (MIL-101(Fe)-NH2 NPs) with sodium lignosulfonate (SL) as a pH/laccase double stimuli-responsive pesticide release system. The average particle size of the prepared chlorfenapyr (CF)-loaded nanoparticles (CF@MIL-101-SL NPs) was 161.54 nm, and the loading efficiency was 44.52%. Bioactivity assays showed that CF@MIL-101-SL NPs increased the toxicity of CF to S. frugiperda and caused the rupture of the peritrophic membrane and enlargement of the midgut. Data from 16S rRNA gene sequencing showed that CF@MIL-101-SL treatment reduced the resistance of S. frugiperda to pesticides and pathogens and affected nutrient and energy availability by remodeling the intestinal microbiota of S. frugiperda. The dysregulated microbial community interacted with the broken peritrophic membrane, which exacerbated damage to the host. Nontargeted metabolomic results showed that ABC transporters may be a potential mechanism for the enhanced toxicity of CF@MIL-101-SL to S. frugiperda. In summary, the present study provides effective strategies for toxicological studies of nanopesticides against insects.PMID:37488665 | DOI:10.1021/acsami.3c07598

Nat Aging. 2023 Jul 24. doi: 10.1038/s43587-023-00460-8. Online ahead of print.ABSTRACTAdipose tissues are central in controlling metabolic homeostasis and failure in their preservation is associated with age-related metabolic disorders. The exact role of mature adipocytes in this phenomenon remains elusive. Here we describe the role of adipose branched-chain amino acid (BCAA) catabolism in this process. We found that adipocyte-specific Crtc2 knockout protected mice from age-associated metabolic decline. Multiomics analysis revealed that BCAA catabolism was impaired in aged visceral adipose tissues, leading to the activation of mechanistic target of rapamycin complex (mTORC1) signaling and the resultant cellular senescence, which was restored by Crtc2 knockout in adipocytes. Using single-cell RNA sequencing analysis, we found that age-associated decline in adipogenic potential of visceral adipose tissues was reinstated by Crtc2 knockout, via the reduction of BCAA-mTORC1 senescence-associated secretory phenotype axis. Collectively, we propose that perturbation of BCAA catabolism by CRTC2 is critical in instigating age-associated remodeling of adipose tissue and the resultant metabolic decline in vivo.PMID:37488415 | DOI:10.1038/s43587-023-00460-8

Sci Rep. 2023 Jul 24;13(1):11981. doi: 10.1038/s41598-023-38669-7.ABSTRACTAnimals and their gut microbes mutually benefit their health. Nutrition plays a central role in this, directly influencing both host and microbial fitness and the nature of their interactions. This makes nutritional symbioses a complex and dynamic tri-system of diet-microbiota-host. Despite recent discoveries on this field, full control over the interplay among these partners is challenging and hinders the resolution of fundamental questions, such as how to parse the gut microbes' effect as raw nutrition or as symbiotic partners? To tackle this, we made use of the well-characterized Drosophila melanogaster/Lactiplantibacillus plantarum experimental model of nutritional symbiosis to generate a quantitative framework of gut microbes' effect on the host. By coupling experimental assays and Random Forest analysis, we show that the beneficial effect of L. plantarum strains primarily results from the active relationship as symbionts rather than raw nutrients, regardless of the bacterial strain. Metabolomic analysis of both active and inactive bacterial cells further demonstrated the crucial role of the production of beneficial bacterial metabolites, such as N-acetylated-amino-acids, as result of active bacterial growth and function. Altogether, our results provide a ranking and quantification of the main bacterial features contributing to sustain animal growth. We demonstrate that bacterial activity is the predominant and necessary variable involved in bacteria-mediated benefit, followed by strain-specific properties and the nutritional potential of the bacterial cells. This contributes to elucidate the role of beneficial bacteria and probiotics, creating a broad quantitative framework for host-gut microbiome that can be expanded to other model systems.PMID:37488173 | DOI:10.1038/s41598-023-38669-7

Phytochemistry. 2023 Jul 22:113790. doi: 10.1016/j.phytochem.2023.113790. Online ahead of print.ABSTRACTNatural complex substances (NCSs) are a heterogeneous family of substances that are notably used as ingredients in several products classified as food supplements, medical devices, cosmetics and traditional medicines, according to the correspondent regulatory framework. The compositions of NCSs vary widely and hundreds to thousands of compounds can be present at the same time. A key concept is that NCSs are much more than the simple sum of the compounds that constitute them, in fact some emerging phenomena are the result of the supramolecular interaction of the constituents of the system. Therefore, close attention should be paid to produce and characterize these systems. Today many natural compounds are produced by chemical synthesis and are intentionally added to NCSs, or to formulated natural products, to enhance their properties, lowering their production costs. Market analysis shows a tendency of people to use products made with NCSs and, currently, products made with ingredients of natural origin only are not conveniently distinguishable from those containing compounds of synthetic origin. Furthermore, the uncertainty of the current European regulatory framework does not allow consumers to correctly differentiate and identify products containing only ingredients of natural origin. The high demand for specific and effective NCSs and their high-cost offer on the market, create the conditions to economically motivated sophistications, characterized by the addition of a cheap material to a more expensive one, just to increase profit. This type of practice can concern both the addition of less valuable natural materials and the addition of pure artificial compounds with the same structure as those naturally present. In this scenario, it becomes essential for producers of natural products to have advanced analytical techniques to evaluate the effective naturalness of NCSs. In fact, synthetically obtained compounds are not identical to their naturally occurring counterparts, due to the isotopic composition or chirality, as well as the presence of different trace metabolites (since pure substances in nature do not exist). For this reason, in this review, the main analytical tests that can be performed to differentiate natural compounds from their synthetic counterparts will be highlighted and the main analytical technologies will be described. At the same time, the main fingerprint techniques useful for characterizing the complexity of the NCSs, also allowing their identification and quali-quantitative evaluation, will be described. Furthermore, NCSs can be produced through different manufacturing processes, not all of which are on the same level of quality. In this review the most suitable technologies for green processes that operate according to physical extraction principles will be presented, as according to the authors they are the ones that come closest to creating more life-cycle compatible NCSs and that are well suited to the European green deal, a strategy with the aim of transforming the EU into a sustainable and resource-efficient society by 2050.PMID:37487919 | DOI:10.1016/j.phytochem.2023.113790

Sci Total Environ. 2023 Jul 22:165695. doi: 10.1016/j.scitotenv.2023.165695. Online ahead of print.ABSTRACTExposure to sub-inhibitory concentrations (sub-MICs) of antibiotics could induce the biofilm formation of microorganisms, but its underlying mechanisms still remain elusive. In the present work, biofilm formation by Salmonella Typhimurium M3 was increased when in the presence of tetracycline at sub-MIC, and the highest induction was observed with tetracycline at 1/8 MIC. The integration of RNA-sequencing and untargeted metabolomics was applied in order to further decipher the potential mechanisms for this observation. In total, 439 genes and 144 metabolites of S. Typhimurium M3 were significantly expressed after its exposure to 1/8 MIC of tetracycline. In addition, the co-expression analysis revealed that 6 genes and 8 metabolites play a key role in response to 1/8 MIC of tetracycline. The differential genes and metabolites were represented in 12 KEGG pathways, including five pathways of amino acid metabolism (beta-alanine metabolism, tryptophan metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glutathione metabolism), three lipid metabolism pathways (biosynthesis of unsaturated fatty acids, fatty acid degradation, and fatty acid biosynthesis), two nucleotide metabolism pathways (purine metabolism, and pyrimidine metabolism), pantothenate and CoA biosynthesis, and ABC transporters. Metabolites (anthranilate, indole, and putrescine) from amino acid metabolism may act as signaling molecules to promote the biofilm formation of S. Typhimurium M3. The results of this work highlight the importance of low antimicrobial concentrations on foodborne pathogens of environmental origin.PMID:37487904 | DOI:10.1016/j.scitotenv.2023.165695

Environ Pollut. 2023 Jul 22:122245. doi: 10.1016/j.envpol.2023.122245. Online ahead of print.ABSTRACTMussels were collected from four coastal sites around Port Phillip Bay, Australia in Mar and Apr 2021). Body burdens of Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) were measured and the possible sources of toxicants discussed. In addition, a gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics analysis was performed using the mantle tissues of mussels. Correlations between the results of contaminant body burdens and metabolic variations were investigated. The results demonstrated that high accumulations of low-molecular-weight PAHs were found in mussels. High body burdens of PCBs and OCPs were only found at mussels from the site close to the river mouth. Some of the metabolic pathways were correlated with the accumulation of PAHs. No correlations were found between PCB and OCP accumulations and metabolic abundances. According to the food and environmental standards of the European Union (EU), the PAH, PCB, and OCP accumulation in mussels in this study are a serious food safety concern.PMID:37487873 | DOI:10.1016/j.envpol.2023.122245