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16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/02PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/02PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/01PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

60 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/11/29PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The Target of Rapamycin kinase affects biomass accumulation and cell cycle progression by altering carbon/nitrogen balance in synchronized Chlamydomonas reinhardtii cells. Plant J. 2017 Nov 24;: Authors: Jüppner J, Mubeen U, Leisse A, Caldana C, Wiszniewski A, Steinhauser D, Giavalisco P Abstract Several metabolic processes tightly regulate growth and biomass accumulation. A highly conserved protein complex containing the Target of Rapamycin (TOR) kinase is known to integrate intra- and extra-cellular stimuli controlling nutrient allocation and hence cellular growth. Although, several functions of TOR have been described in various heterotrophic eukaryotes, our understanding lags far behind in photosynthetic organisms. In the present investigation, we used the model alga Chlamydomonas reinhardtii to conduct a time-resolved analysis of molecular and physiological features throughout the diurnal cycle after TOR inhibition. Detailed examination of the cell cycle phases revealed that growth is not only repressed by 50% but also that significant, nonlinear delays in the progression can be observed. By using metabolomics analysis, we elucidated that the growth repression was mainly driven by differential carbon partitioning between anabolic and catabolic processes. Accordingly, the time-resolved analysis illustrated that metabolic processes including amino acid-, starch- and triacylglycerol synthesis, as well RNA degradation, were redirected within minutes of TOR inhibition. Here especially the high accumulation of nitrogen containing compounds indicated that an active TOR kinase controls the carbon to nitrogen balance of the cell, which is responsible for biomass accumulation, growth and cell cycle progression. This article is protected by copyright. All rights reserved. PMID: 29172247 [PubMed - as supplied by publisher]

Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety. Bioanalysis. 2017 Nov 24;: Authors: Wotherspoon AT, Safavi-Naeini M, Banati RB Abstract This review discusses the use of stable ((13)C, (2)D) or radioactive isotopes ((14)C, (11)C, (18)F, (131)I, (64)Cu, (68)Ga) incorporated into the molecular structure of new drug entities for the purpose of pharmacokinetic or -dynamic studies. Metabolite in safety testing requires the administration of pharmacologically active doses. In such studies, radiotracers find application mainly in preclinical animal investigations, whereby LC-MS/MS is used to identify metabolite structure and drug-related effects. In contrast, first-in-human metabolite studies have to be carried out at nonpharmacological doses not exceeding 100 μg (microdose), which is generally too low for metabolite detection by LC-MS/MS. This short-coming can be overcome by specific radio- or isotopic labeling of the drug of interest and measurements using accelerator mass spectroscopy, single-photon emission computed tomography and positron emission tomography. Such combined radioisotope-based approaches permit Phase 0, first-in-human metabolite study. PMID: 29171759 [PubMed - as supplied by publisher]

[Analysis of influencing factors of secondary metabolites contents in cultivated Polygala tenuifolia]. Zhongguo Zhong Yao Za Zhi. 2017 Aug;42(16):3167-3177 Authors: Pu YJ, Wang DD, Yan Y, Tian HL, Peng B, Qin XM, Ma CG, Du CH, Hu BX, Zhang FS Abstract This work was launched to explore the effect of habitat and growth year on the secondary metabolites contents of cultivated Polygala tenuifolia. The samples of cultivated P. tenuifolia were analyzed by ultra-high performance liquid chromatography(UPLC)-quadrupole time-of-flight mass spectrometry(Q-TOF MS), and the obtained data were analyzed using multiple statistical analysis and cluster analysis. The results showed that compared with growth year, habitat is a main influencing factor which affected the secondary metabolites contents of P. tenuifolia. The contents of sucrose esters and oligosacchride multi-esters are greatly dependent on the habitat (the sample-AG with high levels of components of tenuifoliside B and tenuifoliside C, and the sample-FY with high levels of 3,6'-disinapoyl sucrose, tenuifoliose S, tenuifoliose L, and tenuifoliose V). There is no obvious effect of habitat and growth year on xanthone. The contents of triterpene saponins are greatly dependent on the growth year, and the content of parts of triterpene saponins increased as time goes on.The result indicated that the effect of habitat and growth year on different types of secondary metabolites is not completely equivalent. This study will contribute to the breeding of P. tenuifolia and amendment of current commodity criteria. PMID: 29171237 [PubMed - in process]

Joining the Dots between Omics and Environmental Management. Integr Environ Assess Manag. 2017 Nov 24;: Authors: Leung KMY Abstract With the rapid advancement of DNA sequencing technologies and substantial reduction of their running costs, environmental genomics and transcriptomics become more affordable and popular in environmental toxicology. In parallel, there are also speedy improvements of mass spectrometry and nuclear magnetic resonance spectrometry, enabling high-throughput analyses of proteins and metabolites in biological samples and promoting research studies in proteomics and metabolomics. By applying these high throughput omics technologies, researchers can quickly generate an unprecedentedly vast amount of biological data that may be useful to environmental management. However, the current pace of applying omics information in environmental management is still very slow, and lags well behind the rapid development of omics-based research. This commentary, therefore, timely calls for joint efforts to increase this pace and join the dots between omics and environmental management, turning omics into practical tools. Herein, I explore how omics can contribute to risk assessment and management of chemicals, and recommend what we can do to facilitate and promote the use of omics information in environmental management. This article is especially dedicated to my role model, mentor and friend, Dr. Peter M. Chapman (1951-2017) who sadly passed away on 26 September 2017. This article is protected by copyright. All rights reserved. PMID: 29171160 [PubMed - as supplied by publisher]

Effect of Dietary Forage to Concentrate Ratios on Dynamic Profile Changes and Interactions of Ruminal Microbiota and Metabolites in Holstein Heifers. Front Microbiol. 2017;8:2206 Authors: Zhang J, Shi H, Wang Y, Li S, Cao Z, Ji S, He Y, Zhang H Abstract A better understanding of global ruminal microbiota and metabolites under extensive feeding conditions is a prerequisite for optimizing rumen function and improving ruminant feed efficiency. Furthermore, the gap between the information on the ruminal microbiota and metabolites needs to be bridged. The aim of this study was to investigate the effects of a wide range of forage to concentrate ratios (F:C) on changes and interactions of ruminal microbiota and metabolites. Four diets with different F:C (80:20, 60:40, 40:60, and 20:80) were limit-fed to 24 Holstein heifers, and Illumina MiSeq sequencing and gas chromatography time-of-flight/mass spectrometry were used to investigate the profile changes of the ruminal microbes and metabolites, and the interaction between them. The predominant bacterial phyla in the rumen were Bacteroidetes (57.2 ± 2.6%) and Firmicutes (26.8 ± 1.6%), and the predominant anaerobic fungi were Neocallimastigomycota (64.3 ± 3.8%) and Ascomycota (22.6 ± 2.4%). In total, 44, 9, 25, and 2 genera, respectively, were identified as the core rumen bacteria, ciliate protozoa, anaerobic fungi, and archaea communities across all samples. An increased concentrate level linearly decreased the relative abundance of cellulolytic bacteria and ciliates, namely Fibrobacter, Succinimonas, Polyplastron, and Ostracodinium (q < 0.05), and linearly increased the relative abundance of Entodinium (q = 0.04), which is a non-fibrous carbohydrate degrader. Dietary F:C had no effect on the communities of anaerobic fungi and archaea. Rumen metabolomics analysis revealed that ruminal amino acids, lipids, organic acids, and carbohydrates were altered significantly by altering the dietary F:C. With increasing dietary concentrate levels, the proportions of propionate and butyrate linearly increased in the rumen (P ≤ 0.01). Correlation analysis revealed that there was some utilization relationship or productive association between candidate metabolites and affected microbe groups. This study provides a better understanding of ruminal microbiota and metabolites under a wide range of dietary F:C, which could further reveal integrative information of rumen function and lead to an improvement in ruminant production. PMID: 29170660 [PubMed]

Genome-wide identification and differential analysis of translational initiation. Nat Commun. 2017 Nov 23;8(1):1749 Authors: Zhang P, He D, Xu Y, Hou J, Pan BF, Wang Y, Liu T, Davis CM, Ehli EA, Tan L, Zhou F, Hu J, Yu Y, Chen X, Nguyen TM, Rosen JM, Hawke DH, Ji Z, Chen Y Abstract Translation is principally regulated at the initiation stage. The development of the translation initiation (TI) sequencing (TI-seq) technique has enabled the global mapping of TIs and revealed unanticipated complex translational landscapes in metazoans. Despite the wide adoption of TI-seq, there is no computational tool currently available for analyzing TI-seq data. To fill this gap, we develop a comprehensive toolkit named Ribo-TISH, which allows for detecting and quantitatively comparing TIs across conditions from TI-seq data. Ribo-TISH can also predict novel open reading frames (ORFs) from regular ribosome profiling (rRibo-seq) data and outperform several established methods in both computational efficiency and prediction accuracy. Applied to published TI-seq/rRibo-seq data sets, Ribo-TISH uncovers a novel signature of elevated mitochondrial translation during amino-acid deprivation and predicts novel ORFs in 5'UTRs, long noncoding RNAs, and introns. These successful applications demonstrate the power of Ribo-TISH in extracting biological insights from TI-seq/rRibo-seq data. PMID: 29170441 [PubMed - in process]

Phase modulated 2D HSQC-TOCSY for unambiguous assignment of overlapping spin systems. J Magn Reson. 2017 Nov 14;286:10-16 Authors: Singh A, Dubey A, Adiga SK, Atreya HS Abstract We present a new method that allows one to unambiguously resolve overlapping spin systems often encountered in biomolecular systems such as peptides and proteins or in samples containing a mixture of different molecules such as in metabolomics. We address this problem using the recently proposed phase modulation approach. By evolving the (1)H chemical shifts in a conventional two dimensional (2D) HSQC-TOCSY experiment for a fixed delay period, the phase/intensity of set of cross peaks belonging to one spin system are modulated differentially relative to those of its overlapping counterpart, resulting in their discrimination and recognition. The method thus accelerates the process of identification and resonance assignment of individual compounds in complex mixtures. This approach facilitated the assignment of molecules in the embryo culture medium used in human assisted reproductive technology. PMID: 29169027 [PubMed - as supplied by publisher]

Analysing and navigating natural products space for generating small, diverse, but representative chemical libraries. Biotechnol J. 2017 Nov 23;: Authors: O'Hagan S, Kell DB Abstract BACKGROUND: Armed with the digital availability of two natural products libraries, amounting to some 195,885 molecular entities, we ask the question of how we can best sample from them to maximise their 'representativeness' in smaller and more usable libraries of 96, 384, 1152 and 1920 molecules. Purpose and scope. The term 'representativeness' is intended to include diversity, but for numerical reasons (and the likelihood of being able to perform a QSAR) it is necessary to focus on areas of chemical space that are more highly populated. New synthesis. Encoding chemical structures as fingerprints using the RDKit 'patterned' algorithm, we first assess the granularity of the natural products space using a simple clustering algorithm, showing that there are major regions of 'denseness' but also a great many very sparsely populated areas. We then apply a 'hybrid' hierarchical K-means clustering algorithm to the data to produce more statistically robust clusters from which representative and appropriate numbers of samples may be chosen. There is necessarily again a trade-off between cluster size and cluster number, but within these constraints, libraries containing 384 or 1152 molecules can be found that come from clusters that represent some 18 and 30% of the whole chemical space, with cluster sizes of, respectively, 50 and 27 or above, just about sufficient to perform a QSAR. By using the online availability of molecules via the Molport system (www.molport.com), we were also able to construct (and, for the first time, provide the contents of) a small virtual library of available molecules that provided effective coverage of the chemical space described. Consistent with this, the average molecular similarities of the contents of the libraries developed is considerably smaller than was that of the original libraries. CONCLUSION: The suggested libraries may have use in molecular or phenotypic screening, including for determining possible transporter substrates. PMID: 29168302 [PubMed - as supplied by publisher]

Metabolomic analysis of the toxic effect of chronic exposure of cadmium on rat urine. Environ Sci Pollut Res Int. 2017 Nov 22;: Authors: Chen S, Zhang M, Bo L, Li S, Hu L, Zhao X, Sun C Abstract This study aimed to assess the toxic effect of chronic exposure to cadmium through a metabolomic approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). Forty male Sprague-Dawley rats were randomly assigned to the following groups: control, low-dose cadmium chloride (CdCl2) (0.13 mg/kg body weight (bw)), middle-dose CdCl2 (0.8/kg bw), and high-dose CdCl2 (4.9 mg/kg bw). The rats continuously received CdCl2 via drinking water for 24 weeks. Rat urine samples were then collected at different time points to establish the metabolomic profiles. Multiple statistical analyses with principal component analysis and partial least squares-discriminant analysis were used to investigate the metabolomic profile changes in the urine samples and screen for potential biomarkers. Thirteen metabolites were identified from the metabolomic profiles of rat urine after treatment. Compared with the control group, the treated groups showed significantly increased intensities of phenylacetylglycine, guanidinosuccinic acid, 4-pyridoxic acid, 4-aminohippuric acid, 4-guanidinobutanoic acid, allantoic acid, dopamine, LysoPC(18:2(9Z,12Z)), and L-urobilinogen. By contrast, the intensities of creatinine, L-carnitine, taurine, and pantothenic acid in the treated groups were significantly decreased. These results indicated that Cd disrupts energy and lipid metabolism. Meanwhile, Cd causes liver and kidney damage via induction of oxidative stress; serum biochemical indices (e.g., creatinine and urea nitrogen) also support the aforementioned results. PMID: 29168138 [PubMed - as supplied by publisher]

Potential of dynamically harmonized Fourier transform ion cyclotron resonance cell for high-throughput metabolomics fingerprinting: control of data quality. Anal Bioanal Chem. 2017 Nov 22;: Authors: Habchi B, Alves S, Jouan-Rimbaud Bouveresse D, Appenzeller B, Paris A, Rutledge DN, Rathahao-Paris E Abstract Due to the presence of pollutants in the environment and food, the assessment of human exposure is required. This necessitates high-throughput approaches enabling large-scale analysis and, as a consequence, the use of high-performance analytical instruments to obtain highly informative metabolomic profiles. In this study, direct introduction mass spectrometry (DIMS) was performed using a Fourier transform ion cyclotron resonance (FT-ICR) instrument equipped with a dynamically harmonized cell. Data quality was evaluated based on mass resolving power (RP), mass measurement accuracy, and ion intensity drifts from the repeated injections of quality control sample (QC) along the analytical process. The large DIMS data size entails the use of bioinformatic tools for the automatic selection of common ions found in all QC injections and for robustness assessment and correction of eventual technical drifts. RP values greater than 10(6) and mass measurement accuracy of lower than 1 ppm were obtained using broadband mode resulting in the detection of isotopic fine structure. Hence, a very accurate relative isotopic mass defect (RΔm) value was calculated. This reduces significantly the number of elemental composition (EC) candidates and greatly improves compound annotation. A very satisfactory estimate of repeatability of both peak intensity and mass measurement was demonstrated. Although, a non negligible ion intensity drift was observed for negative ion mode data, a normalization procedure was easily applied to correct this phenomenon. This study illustrates the performance and robustness of the dynamically harmonized FT-ICR cell to perform large-scale high-throughput metabolomic analyses in routine conditions. Graphical abstract Analytical performance of FT-ICR instrument equipped with a dynamically harmonized cell. PMID: 29167936 [PubMed - as supplied by publisher]

Towards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolites. Phytochem Rev. 2017;16(5):935-951 Authors: Mouden S, Klinkhamer PGL, Choi YH, Leiss KA Abstract With mounting concerns over health and environmental effects of pesticides, the search for environmentally acceptable substitutes has amplified. Plant secondary metabolites appear in the horizon as an attractive solution for green crop protection. This paper reviews the need for changes in the techniques and compounds that, until recently, have been the mainstay for dealing with pest insects. Here we describe and discuss main strategies for selecting plant-derived metabolites as candidates for sustainable agriculture. The second part surveys ten important insecticidal compounds, with special emphasis on those involved in human health. Many of these insecticidal metabolites, however, are crystalline solids with limited solubility which might potentially hamper commercial formulation. As such, we introduce the concept of natural deep eutectic solvents for enhancing solubility and stability of such compounds. The concept, principles and examples of green pest control discussed here offer a new suite of environmental-friendly tools designed to promote and adopt sustainable agriculture. PMID: 29167631 [PubMed]

Hyperoxidation of ether-linked phospholipids accelerates neutrophil extracellular trap formation. Sci Rep. 2017 Nov 22;7(1):16026 Authors: Yotsumoto S, Muroi Y, Chiba T, Ohmura R, Yoneyama M, Magarisawa M, Dodo K, Terayama N, Sodeoka M, Aoyagi R, Arita M, Arakawa S, Shimizu S, Tanaka M Abstract Because neutrophil extracellular trap (NET) formation is involved in the pathology of a wide variety of diseases, NET-regulating compounds are expected to be useful for the therapies of these diseases. In this study, we identified sulfasalazine (SSZ) as a potent enhancer of NET formation both in vitro and in vivo. Although SSZ did not increase the amount of ROS generated, it accelerated the generation of ether-linked oxidized phospholipids, such as PE (18;1e/15-HETE) and PC (16;0e/13-HODE). Trolox, but not 2-ME, effectively suppressed lipid oxidation and NET formation that were induced by SSZ. SSZ is known as a potent inducer of ferroptosis in cancer cells by inhibiting xCT, a component of the cystine transporter. However, we found that SSZ accelerated NET formation in an xCT-independent manner. Structure-activity relationship studies revealed that the sulfapyridine moiety of SSZ plays a central role in enhancing NET formation. Furthermore, we found that two additional sulfonamide and sulfone derivatives possess NET-inducing activity by accelerating lipid oxidation. These results indicate that the hyperoxidation of ether-linked phospholipids is a key mechanism for accelerating NET formation. PMID: 29167447 [PubMed - in process]

Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy. Oncotarget. 2017 Oct 27;8(52):89527-89538 Authors: Sica V, Bravo-San Pedro JM, Chen G, Mariño G, Lachkar S, Izzo V, Maiuri MC, Niso-Santano M, Kroemer G Abstract Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions. Depletion of ING4 stimulated the enzymatic activity of PIK3C3, as visualized by means of a red fluorescent protein-tagged short peptide (FYVE) that specifically binds to phosphatidylinositol-3-phosphate (PI3P)-containing subcellular vesicles and enhanced autophagy, as indicated by an enhanced lipidation of microtubule-associated proteins 1A/1B light chain 3 beta (LC3B) and the redistribution of a green-fluorescent protein (GFP)-LC3B fusion protein to cytoplasmic puncta. The generation of GFP-LC3B puncta stimulated by ING4 depletion was reduced by simultaneous depletion, or pharmacological inhibition, of PIK3C3/VPS34. In conclusion, ING4 acts as a negative regulator of the lipid kinase activity of the BECN1 complex, and starvation-induced autophagy is accompanied by the dissociation of the ING4/BECN1 interaction. PMID: 29163768 [PubMed]

Selenium Biofortification in Fragaria × ananassa: Implications on Strawberry Fruits Quality, Content of Bioactive Health Beneficial Compounds and Metabolomic Profile. Front Plant Sci. 2017;8:1887 Authors: Mimmo T, Tiziani R, Valentinuzzi F, Lucini L, Nicoletto C, Sambo P, Scampicchio M, Pii Y, Cesco S Abstract Selenium (Se) is an essential nutrient for humans, due to its antioxidant properties, whereas, to date, its essentiality to plants still remains to be demonstrated. Nevertheless, if added to the cultivation substrate, plants growth resulted enhanced. However, the concentration of Se in agricultural soils is very variable, ranging from 0.01 mg kg(-1) up to 10 mg kg(-1) in seleniferous areas. Therefore several studies have been performed aimed at bio-fortifying crops with Se and the approaches exploited were mainly based on the application of Se fertilizers. The aim of the present research was to assess the biofortification potential of Se in hydroponically grown strawberry fruits and its effects on qualitative parameters and nutraceutical compounds. The supplementation with Se did not negatively affect the growth and the yield of strawberries, and induced an accumulation of Se in fruits. Furthermore, the metabolomic analyses highlighted an increase in flavonoid and polyphenol compounds, which contributes to the organoleptic features and antioxidant capacity of fruits; in addition, an increase in the fruits sweetness also was detected in biofortified strawberries. In conclusion, based on our observations, strawberry plants seem a good target for Se biofortification, thus allowing the increase in the human intake of this essential micronutrient. PMID: 29163609 [PubMed]

Cultivar Diversity of Grape Skin Polyphenol Composition and Changes in Response to Drought Investigated by LC-MS Based Metabolomics. Front Plant Sci. 2017;8:1826 Authors: Pinasseau L, Vallverdú-Queralt A, Verbaere A, Roques M, Meudec E, Le Cunff L, Péros JP, Ageorges A, Sommerer N, Boulet JC, Terrier N, Cheynier V Abstract Phenolic compounds represent a large family of plant secondary metabolites, essential for the quality of grape and wine and playing a major role in plant defense against biotic and abiotic stresses. Phenolic composition is genetically driven and greatly affected by environmental factors, including water stress. A major challenge for breeding of grapevine cultivars adapted to climate change and with high potential for wine-making is to dissect the complex plant metabolic response involved in adaptation mechanisms. A targeted metabolomics approach based on ultra high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QqQ-MS) analysis in the Multiple Reaction Monitoring (MRM) mode has been developed for high throughput profiling of the phenolic composition of grape skins. This method enables rapid, selective, and sensitive quantification of 96 phenolic compounds (anthocyanins, phenolic acids, stilbenoids, flavonols, dihydroflavonols, flavan-3-ol monomers, and oligomers…), and of the constitutive units of proanthocyanidins (i.e., condensed tannins), giving access to detailed polyphenol composition. It was applied on the skins of mature grape berries from a core-collection of 279 Vitis vinifera cultivars grown with or without watering to assess the genetic variation for polyphenol composition and its modulation by irrigation, in two successive vintages (2014-2015). Distribution of berry weights and δ(13)C values showed that non irrigated vines were subjected to a marked water stress in 2014 and to a very limited one in 2015. Metabolomics analysis of the polyphenol composition and chemometrics analysis of this data demonstrated an influence of water stress on the biosynthesis of different polyphenol classes and cultivar differences in metabolic response to water deficit. Correlation networks gave insight on the relationships between the different polyphenol metabolites and related biosynthetic pathways. They also established patterns of polyphenol response to drought, with different molecular families affected either positively or negatively in the different cultivars, with potential impact on grape and wine quality. PMID: 29163566 [PubMed]

Efficacy and Safety of a Multistrain Probiotic Formulation Depends from Manufacturing. Front Immunol. 2017;8:1474 Authors: Trinchieri V, Laghi L, Vitali B, Parolin C, Giusti I, Capobianco D, Mastromarino P, De Simone C Abstract Background: Variability in probiotics manufacturing may affect their properties, with potential implications for their efficacy and safety. This is of particular concern with probiotic products destined for use in patients with serious medical conditions, including human immunodeficiency virus (HIV) infection. The purpose of the study was to carry out a series of experiments comparing the properties of the US-made probiotic formulation originally commercialized under the brand name VSL#3(®), with those of the Italian-made formulation now commercialized under the same name. The US-made formulation has previously shown beneficial effects at the intestinal and neurological levels in HIV-infected subjects as well as in patients with inflammatory bowel diseases and hepatic encephalopathy. Methods: Eleven subjects receiving combined antiretroviral therapy for HIV-1 were treated for 6 months with the US-made VSL#3 formulation. At baseline and 6 months, T-cells were analyzed for phenotype and activation markers, and fecal samples were analyzed for bifidobacteria, lactobacilli, and their metabolites. The fecal metabolome was assessed using (1)H-NMR spectroscopy. Production of metabolites of interest by bacteria obtained from sachets of the two formulations was compared in vitro and their effects on a rat intestinal epithelial cell line (IEC-6) were assessed. Particular attention was paid to the metabolite 1,3-dihydroxyacetone (DHA). Results: At 6 months, fecal samples showed a significant increase in the specific bacterial genera contained in the probiotic supplement. Immune activation was reduced as shown by a significant reduction in the percentage of CD4(+)CD38(+)HLA-DR(+) T-cells at 6 months. Fecal concentrations of DHA decreased significantly. In vitro, significant differences in the production and metabolism of DHA were found between bacteria from the US-made and Italian-made formulations: the US-made formulation was able to metabolize DHA whereas the bacteria in the Italian-made formulation were producing DHA. DHA reduced the viability of Streptococcus thermophilus, reduced IEC-6 cell viability in a dose-dependent manner, and also led to a lower rate of repair to scratched IEC-6 cell monolayer. Conclusion: Our data, in conjunction with previously published findings, confirm that the new Italian-made formulation of VSL#3(®) is different from the previous US-made VSL#3 and therefore its efficacy and safety in HIV-infected subjects is still unproven. PMID: 29163538 [PubMed]