Antonis Myridakis - Academia.edu (original) (raw)

Papers by Antonis Myridakis

Introduction: Bisphenol A (BPA) is a chemical used extensively worldwide in the manufacture of pl... more Introduction: Bisphenol A (BPA) is a chemical used extensively worldwide in the manufacture of plastic polymers. The environmental obesogen hypothesis suggests that early life exposure to endocrine...

ISEE Conference Abstracts

Introduction: Phthalates are industrial chemicals with endocrine disrupting properties. Human evi... more Introduction: Phthalates are industrial chemicals with endocrine disrupting properties. Human evidence on the effects of early life phthalate exposure on obesity and cardiovascular risks is limited...

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2020

Tyrosine plays a key role in mammalian biochemistry and defects in its metabolism (e.g., tyrosine... more Tyrosine plays a key role in mammalian biochemistry and defects in its metabolism (e.g., tyrosinemia, alkaptonuria etc.) have significant adverse consequences for those affected if left untreated. In addition, gut bacterially-derived p-cresol and its metabolites are of interest as a result of various effects on host xenobiotic metabolism. A fit-for-purpose quantitative ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was developed to target and quantify tyrosine and eleven metabolites in urine and plasma. Dansylation, using dansyl chloride, was used to improve chromatographic and mass spectral properties for tyrosine and nine phenolic metabolites, with detection using positive electrospray ionisation (ESI). The sulfate and glucuronide conjugates of p-cresol, where the phenol group was blocked, were quantified intact, using negative ESI via polarity switching during the same run. Sample preparation for urine and plasma involved deproteinization by s...

1 pasteurized bacterium improves metabolism in obese and diabetic mice 2 3 Hubert Plovier, Amandi... more 1 pasteurized bacterium improves metabolism in obese and diabetic mice 2 3 Hubert Plovier, Amandine Everard, Céline Druart, Clara Depommier, Matthias Van Hul, 4 Lucie Geurts, Julien Chilloux, Noora Ottman, Thibaut Duparc, Laeticia Lichtenstein, 5 Antonis Myridakis, Nathalie M. Delzenne, Judith Klievink Arnab Bhattacharjee, Kees C.H. 6 van der Ark, Steven Aalvink, Laurent O. Martinez, Marc-Emmanuel Dumas, Dominique 7 Maiter, Audrey Loumaye, Michel P. Hermans, Jean-Paul Thissen, Clara Belzer, Willem M. 8 de Vos, Patrice D. Cani 9

Nature Protocols

The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection... more The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection and monitoring is an emergent research field that has the potential to reshape current clinical practice. However, adoption of breath testing has been limited by a lack of standardization. This protocol provides a comprehensive workflow for online and offline breath analysis using selected ion flow tube mass spectrometry (SIFT-MS). Following the suggested protocol, 50 human breath samples can be analyzed and interpreted in <3 h. Key advantages of SIFT-MS are exploited, including the acquisition of real-time results and direct compound quantification without need for calibration curves. The protocol includes details of methods developed for targeted analysis of disease-specific VOCs, specifically short-chain fatty acids, aldehydes, phenols, alcohols and alkanes. A procedure to make custom breath collection bags is also described. This standardized protocol for VOC analysis using SIFT-MS is intended to provide a basis for wider application and the use of breath analysis in clinical studies.

Journal of Breath Research

This paper comprises an updated version of the 2014 review which reported 1846 volatile organic c... more This paper comprises an updated version of the 2014 review which reported 1846 volatile organic compounds (VOCs) identified from healthy humans. In total over 900 additional VOCs have been reported since the 2014 review and the VOCs from semen have been added. The numbers of VOCs found in breath and the other bodily fluids are: blood 379, breath 1488, faeces 443, milk 290, saliva 549, semen 196, skin 623 and urine 444. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been included in a single table with the source reference(s) for each VOC, an update on our 2014 paper. VOCs have also been grouped into tables according to their chemical class or functionality to permit easy comparison. Careful use of the database is needed, as a number of the identified VOCs only have level 2—putative assignment, and only a small fraction of the reported VOCs have been validated by standards. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces and breath. However, the lack of compounds from matrices such a semen and milk compared to breath for example could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from milk and semen compared to a large number for breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. by collecting skin sebum (with dissolved VOCs and semi VOCs) onto glass beads or cotton pads and then heating to a high temperature to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors’ intention that this work will not only be a useful database of VOCs listed in the literature but will stimulate further study of VOCs from healthy individuals; for example more work is required to confirm the identification of these VOCs adhering to the principles outlined in the metabolomics standards initiative. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.

Scientific Reports

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker... more Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In...

ABSTRACTBackgroundAutism Spectrum Disorders (ASD) are associated with dysregulation of the microb... more ABSTRACTBackgroundAutism Spectrum Disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis resulting in changes in microbiota composition as well as fecal, serum and urine levels of microbial metabolites. Yet, a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.ResultsMice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-t...

Metabolites

The analysis of urinary volatile organic compounds (VOCs) is a promising field of research with t... more The analysis of urinary volatile organic compounds (VOCs) is a promising field of research with the potential to discover new biomarkers for cancer early detection. This systematic review aims to summarise the published literature concerning cancer-associated urinary VOCs. A systematic online literature search was conducted to identify studies reporting urinary VOC biomarkers of cancers in accordance with the recommendations of the Cochrane Library and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Thirteen studies comprising 1266 participants in total were included in the review. Studies reported urinary VOC profiles of five cancer subtypes: prostate cancer, gastrointestinal cancer, leukaemia/lymphoma, lung cancer, and bladder cancer. Forty-eight urinary VOCs belonging to eleven chemical classes were identified with high diagnostic performance. VOC profiles were distinctive for each cancer type with limited cross-over. The metabolic analysis suggested di...

Poster presentations

binds FcgRs, as well as some nuclear proteins, including snRNPs. Pentameric (native) CRP has prev... more binds FcgRs, as well as some nuclear proteins, including snRNPs. Pentameric (native) CRP has previously been suggested to inhibit production of IFNs in peripheral mononuclear cells (PBMCs) in response to ICs formed by autoantibodies against snRNP, an effect which was further investigated herein. Methods PBMCs or magnetically (MACS) purified pDCs were retrieved from whole blood of healthy volunteers. Type I IFN gene transcription and production was stimulated by addition of snRNP containing ICs ± pentameric CRP (pCRP) or monomeric CRP (mCRP) in different sequential order. IC formation was achieved through simultaneous addition of snRNP and bulk IgG, retrieved from an SLE patient with high levels of snRNP autoantibodies, directly to the cells. Type I IFNs and inflammatory cytokines were investigated using quantitative PCR, ELISA and cytometric bead array, and cells responsible for production of the IFNs were characterized using flow cytometry. For statistics a two-tailed t-test was performed. Results pCRP had an inhibitory effect on the IFN gene expression in PBMCs after incubation with ICs, p=0.044 for IFNa4 and p=0.047 for IFNb at the 4h time-point compared to IC only. pCRP also showed a dose-dependent inhibitory effect on the type I IFN production in the cells. The monomeric form of CRP showed modest or no effect on IFN levels, p=0.82 for IFNa4 and p=0.58 for IFNb at the 4h time-point compared to IC only. A pre-incubation of the cells with pCRP increased the inhibitory effects compared to simultaneous addition of pCRP and ICs, suggesting that initial binding to the cells is a critical step for inhibition. Flow cytometry suggested that pDCs are the main producer of the type I IFNs. In addition, pCRP seems to have a more general inhibitory effect on type I IFNs, as seen in the reduction of IFN production in response to the TLR-9 ligand CpG. Conclusions pCRP has a distinct inhibitory effect on type I IFNs, which is largely not seen for the dissociated form of CRP (mCRP). The more general inhibitory effects shown by pCRP highlights its immune regulatory function in pathologies characterized by high production of type I IFNs. The identity of the initial receptors responsible for pCRP mediated effects, as well as of the involved signaling pathways, will be further investigated.

Diabetologia

Aims/hypothesis Drug and surgical-based therapies in type 2 diabetes are associated with altered ... more Aims/hypothesis Drug and surgical-based therapies in type 2 diabetes are associated with altered gut microbiota architecture. Here we investigated the role of the gut microbiome in improved glucose homeostasis following bariatric surgery. Methods We carried out gut microbiome analyses in gastrectomised (by vertical sleeve gastrectomy [VSG]) rats of the Goto–Kakizaki (GK) non-obese model of spontaneously occurring type 2 diabetes, followed by physiological studies in the GK rat. Results VSG in the GK rat led to permanent improvement of glucose tolerance associated with minor changes in the gut microbiome, mostly characterised by significant enrichment of caecal Prevotella copri. Gut microbiota enrichment with P. copri in GK rats through permissive antibiotic treatment, inoculation of gut microbiota isolated from gastrectomised GK rats, and direct inoculation of P. copri, resulted in significant improvement of glucose tolerance, independent of changes in body weight. Plasma bile acids...

Referenced abstractThe interaction between high-fat diet (HFD) feeding and the gut microbiome has... more Referenced abstractThe interaction between high-fat diet (HFD) feeding and the gut microbiome has a strong impact on the onset of insulin resistance (IR)1-3. In particular, bacterial lipopolysaccharides (LPS) and dietary fats trigger low-grade inflammation4 through activation of Toll-like receptor 4 (TLR4), a process called metabolic endotoxemia5. However, little is known about how the microbiome can mitigate this process. Here, we investigate longitudinal physiological and metabotypical responses of C57BL/6 mice to HFD feeding. A series of in vivo experiments with choline supplementation, then blocking trimethylamine (TMA) production and administering TMA, demonstrate that this microbiome-associated metabolite decouples inflammation and IR from obesity in HFD. Through in vitro kinome screens and in silico molecular dynamics studies, we reveal TMA specifically inhibits Interleukin-1 Receptor-associated Kinase 4 (IRAK-4), a central kinase integrating signals from various TLRs and cyt...

Acta Diabetologica

The human gut is a home for more than 100 trillion bacteria, far more than all other microbial po... more The human gut is a home for more than 100 trillion bacteria, far more than all other microbial populations resident on the body's surface. The human gut microbiome is considered as a microbial organ symbiotically operating within the host. It is a collection of different cell lineages that are capable of communicating with each other and the host and has an ability to undergo self-replication for its repair and maintenance. As the gut microbiota is involved in many host processes including growth and development, an imbalance in its ecological composition may lead to disease and dysfunction in the human. Gut microbial degradation of nutrients produces bioactive metabolites that bind target receptors, activating signalling cascades, and modulating host metabolism. This review covers current findings on the nutritional and pharmacological roles of selective gut microbial metabolites, short-chain fatty acids, methylamines and indoles, as well as discussing nutritional interventions to modulate the microbiome.

Microbiome

Background: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the ... more Background: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes. Results: A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1 H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture. Conclusions: Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota.

Frontiers in Public Health

Vafeiadi et al. Phthalates, Childhood Obesity, and Cardiometabolic Risk in MiBP was associated wi... more Vafeiadi et al. Phthalates, Childhood Obesity, and Cardiometabolic Risk in MiBP was associated with 4.4% higher total cholesterol levels (95% CI: 0.2, 8.7). Prenatal phthalate exposure was not consistently associated with child adiposity and cardiometabolic measures. Our findings suggest that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner and depends on the timing of exposure.

Nature medicine, 2018

In the version of this article originally published, the P statistic described in Fig. 3d was inc... more In the version of this article originally published, the P statistic described in Fig. 3d was incorrect. It was described as "P < 22 × 10". It should have been "P < 2.2 × 10". Also, the "CD8 Treg" label in Fig. 4f was incorrect. It should have been "CD4 Treg". The errors have been corrected in the HTML and PDF versions of this article.

European Journal of Midwifery

INTRODUCTION Smoking cessation during pregnancy is beneficial to both the mother and child. Our o... more INTRODUCTION Smoking cessation during pregnancy is beneficial to both the mother and child. Our objective was to assess if an intensive smoking cessation intervention for pregnant women increases: a) rates of smoking cessation, and b) reduces exposure to tobacco-specific carcinogens during pregnancy. METHODS A two-group single-blinded parallel randomized controlled trial (RCT) was conducted involving 84 pregnant smokers in either a high intensity (n=42) or minimal contact control group (n=42). Women assigned to the high intensity smoking cessation intervention group received a single 30-minute behavioural counselling session and a tailored self-help booklet. The primary outcome measures were: 7-day point prevalence abstinence measured by selfreport and urine cotinine levels, and maternal tobacco specific carcinogens nitrosamine (NNAL) urine concentrations assessed at 32 weeks of gestation. RESULTS A significantly greater percentage of pregnant smokers quit smoking in the high intensity group compared to the low intensity control group (45.2% vs 21.4%; p=0.001). A significant decrease in urine cotinine concentrations was documented in the experimental group (-140.74 ± 361.70 ng/mL; p=0.004), with no significant decrease documented in the control group. A significant decrease in NNAL levels was also documented in the experimental group (158.17 ± 145.03 pg/mL before, 86.43 ± 112.54 pg/mL after; p=0.032) with no significant changes in the control group. CONCLUSIONS The high intensity intervention tested resulted in significantly greater cessation rates. Intensive smoking cessation interventions can be effective in reducing fetal exposure to NNAL. This is the first trial to report on NNAL tobacco-specific carcinogen concentrations before and after an intervention for smoking cessation during pregnancy.

International journal of cancer, Jan 18, 2018

Recent prospective studies have shown that dysregulation of the immune system may precede the dev... more Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10 )...