PubMed

Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome. 2020 Sep 12;8(1):133 Authors: Seelbinder B, Chen J, Brunke S, Vazquez-Uribe R, Santhaman R, Meyer AC, de Oliveira Lino FS, Chan KF, Loos D, Imamovic L, Tsang CC, Lam RP, Sridhar S, Kang K, Hube B, Woo PC, Sommer MOA, Panagiotou G Abstract BACKGROUND: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing. RESULTS: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate. CONCLUSIONS: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract. PMID: 32919472 [PubMed - in process]

Exhaled volatile organic compounds analysis in clinical pediatrics: a systematic review. Pediatr Res. 2020 Sep 12;: Authors: Martínez RAS, Hernández JMP, Torrado ÓY, Díaz MC, Puente TD, Crevillent MV Abstract BACKGROUND: Measured exhaled volatile organic compounds (VOCs) in-breath also referred to as exhaled volatilome have been long claimed as a potential source of non-invasive and clinically applicable biomarkers. However, the feasibility of using exhaled volatilome in clinical practice remains to be demonstrated, particularly in pediatrics where the need for improved non-invasive diagnostic and monitoring methods is most urgent. This work presents the first formal evidence-based judgment of the clinical potential of breath volatilome in the pediatric population. METHODS: A rigorous systematic review across Web of Science, SCOPUS, and PubMed databases following the PRISMA statement guidelines. A narrative synthesis of the evidence was conducted and QUADAS-2 was used to assess the quality of selected studies. RESULTS: Two independent reviewers deemed 22 out of the 229 records initially found to satisfy inclusion criteria. A summary of breath VOCs found to be relevant for several respiratory, infectious, and metabolic pathologies was conducted. In addition, we assessed their associated metabolism coverage through a functional characterization analysis. CONCLUSION: Our results indicate that current research remains stagnant in a preclinical exploratory setting. Designing exploratory experiments in compliance with metabolomics practice should drive forward the clinical translation of VOCs breath analysis. IMPACT: What is the key message of your article?Metabolomics practice could help to achieve the clinical utility of exhaled volatilome analysis.What does it add to the existing literature?This work is the first systematic review focused on disease status discrimination using analysis of exhaled breath in the pediatric population. A summary of the reported exhaled volatile organic compounds is conducted together with a functional characterization analysis.What is the impact?Having noted challenges preventing the clinical translation, we summary metabolomics practices and the experimental designs that are closer to clinical practice to create a framework to guide future trials.Fig. 1Flow diagram of PRISMA-oriented systematic search and literature records selection.Fig. 2VOCS DISCRIMINANT PROFILE SUMMARIZED ACROSS THE STUDIES INCLUDED IN THE QUALITATIVE SYNTHESIS.: a Asthma or allergic asthma patients vs. healthy controls (HCTR). b Asthma with exacerbations vs. stable patients. c Cystic fibrosis (CF) vs. HCTR.Fig. 3QUALITY ASSESSMENT OF THE INCLUDED STUDIES IN THE QUALITATIVE SYNTHESIS THROUGH QUADAS-2 SCORING SYSTEM.: a Summary for individual studies. Display of b risk of bias and c applicability concerns across different domains. PMID: 32919397 [PubMed - as supplied by publisher]

Targeted and non-targeted unexpected food contaminants analysis by LC/HRMS: Feasibility study on rice. Food Chem. 2020 Sep 03;338:127957 Authors: Wang T, Duedahl-Olesen L, Lauritz Frandsen H Abstract A widely applicable analytical LC/HRMS method based on ion source optimization, data treatment optimization on rice matrix was developed. The effects of key parameters of ion source, and their interactions on ESI response were studied on HPLC-QTOF. Compared with center points, 40% and 20% increase of response factors in the positive and negative mode can be achieved by ion source optimization, respectively. Data processing strategies inspired from metabolomics and multi-targeted analysis were compared and developed using case and control rice samples. Highly automated workflow using XCMS achieved highest mass accuracy, highest detection rate of 96% for 5 μg/kg in a non-targeted way. A clear distinction between the control and contaminated samples by PCA and PLS-DA was also achieved by this workflow using XCMS, even for the concentration of 5 μg/kg. PMID: 32919373 [PubMed - as supplied by publisher]

Corrigendum to "Characterizing metabolites and potential metabolic pathways changes to understanding the mechanism of medicinal plant against doxorubicin-indu Phellodendri amurensis cortexced nephritis rats using UPLC-Q/TOF-MS metabolomics" [J. Pharm. Biomed. Anal. 188 (2020) 1-14/11336]. J Pharm Biomed Anal. 2020 Sep 09;191:113608 Authors: Zhang H, Zhang S, Wang W, Wang Q, Kuang H, Wang Q PMID: 32919142 [PubMed - as supplied by publisher]

Comparative analysis of fecal metabolite profiles in HFD-induced obese mice after oral administration of huangjinya green tea extract. Food Chem Toxicol. 2020 Sep 09;:111744 Authors: Li M, Xu J, Zhang Y, Chu S, Sun S, Huo Y, Zhao J, Hu X, Wan C, Li L Abstract To explore the impact of Huangjinya on metabolic disorders and host endogenous metabolite profiles, high-fat diet (HFD)-fed mice were administrated with Huangjinya green tea extract (HGT) at the dose of 150 or 300 mg/kg for 9 weeks. Epigallocatechin gallate was the main catechin derivative, followed by epigallocatechin and catechin presented in HGT, which contained high levels of free amino acids (50.30 ± 0.60 mg/g). HGT significantly alleviated glucose and insulin intolerance, reduced hepatic lipid accumulation and liver steatosis, and prevented white adipose tissue expansion in HFD-fed mice. Untargeted mass spectrometry-based metabolomics analysis revealed that HGT reduced the abundance of fecal branched-chain amino acids, aromatic amino acids, sphingolipids, and most acyl cholines, modulated bile acid metabolism by increasing chenodeoxycholate and reducing cholic acid content, and increased unsaturated fatty acids content. Fatherly, HGT activated insulin/PI3K/Akt and AMPK signaling pathways in the liver, reduced adipogenic and lipogenic genes expression, and promoted the genes expression related to lipolysis and adipocyte browning in white adipose tissue, contributed to improving metabolic syndrome in HFD-fed mice. The current study reported the impact of HGT supplementation on endogenous metabolite profiles, and highlights the positive roles of HGT in preventing diet-induced obesity and the related metabolic disorders. PMID: 32918987 [PubMed - as supplied by publisher]

Metabolism of prostate cancer by magnetic resonance spectroscopy (MRS). Biophys Rev. 2020 Sep 12;: Authors: Sharma U, Jagannathan NR Abstract Understanding the metabolism of prostate cancer (PCa) is important for developing better diagnostic approaches and also for exploring new therapeutic targets. Magnetic resonance spectroscopy (MRS) techniques have been shown to be useful in the detection and quantification of metabolites. PCa illustrates metabolic phenotype, showing lower levels of citrate (Cit), a key metabolite of oxidative phosphorylation and alteration in several metabolic pathways to sustain tumor growth. Recently, dynamic nuclear polarization (DNP) studies have documented high rates of glycolysis (Warburg phenomenon) in PCa. High-throughput metabolic profiling strategies using MRS on variety of samples including intact tissues, biofluids like prostatic fluid, seminal fluid, blood plasma/sera, and urine have also played a vital role in understanding the abnormal metabolic activity of PCa patients. The enhanced analytical potential of these techniques in the detection and quantification of a large number of metabolites provides an in-depth understanding of metabolic rewiring associated with the tumorigenesis. Metabolomics analysis offers dual advantages of identification of diagnostic and predictive biomarkers as well as in understanding the altered metabolic pathways which can be targeted for inhibiting the cancer progression. This review briefly describes the potential applications of in vivo 1H MRS, high-resolution magic angle spinning spectroscopy (HRMAS) and in vitro MRS methods in understanding the metabolic changes of PCa and its usefulness in the management of PCa patients. PMID: 32918707 [PubMed - as supplied by publisher]

Calystegines are Potential Urine Biomarkers for Dietary Exposure to Potato Products. Mol Nutr Food Res. 2020 Sep 11;:e2000515 Authors: Beckmann M, Lloyd AJ, Wilson T, Torres D, Goios A, Willis ND, Lyons L, Phillips H, Mathers JC, Nash RJ, Sharp H, Draper J Abstract SCOPE: Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). This study investigated the possibility that calystegines (a class of iminosugars) may provide BIFs for potato (Solanum tuberosum L.) product exposure. METHODS AND RESULTS: Calystegine content was examined in published data covering a wide range of potato cultivars. We developed rapid methods for the quantification of calystegines in cooked potato products and human urine using triple quadrupole mass spectrometry. The potential of calystegines as BFIs for potato consumption was assessed in a controlled food intervention study in the UK and validated in an epidemiological study in Portugal. Calystegine concentrations were reproducibly above the quantification limit in first morning void urines the day after potato consumption, showing a good dose-response relationship, particularly for calystegine A3 . The design of the controlled intervention mimicked exposure to a typical UK diet and showed that neither differences in preparation/cooking method or the influence of other foods in the diet had significant impact on biomarker performance. Calystegine biomarkers also performed well in the independent validation study. CONCLUSION: We conclude that calystegines have many of the characteristics needed to be considered as specific BFIs for potato product intake. This article is protected by copyright. All rights reserved. PMID: 32918337 [PubMed - as supplied by publisher]

Metallothionein 1 Overexpression Does Not Protect Against Mitochondrial Disease Pathology in Ndufs4 Knockout Mice. Mol Neurobiol. 2020 Sep 11;: Authors: Miller HC, Louw R, Mereis M, Venter G, Boshoff JD, Mienie L, van Reenen M, Venter M, Lindeque JZ, Domínguez-Martínez A, Quintana A, van der Westhuizen FH Abstract Mitochondrial diseases (MD), such as Leigh syndrome (LS), present with severe neurological and muscular phenotypes in patients, but have no known cure and limited treatment options. Based on their neuroprotective effects against other neurodegenerative diseases in vivo and their positive impact as an antioxidant against complex I deficiency in vitro, we investigated the potential protective effect of metallothioneins (MTs) in an Ndufs4 knockout mouse model (with a very similar phenotype to LS) crossed with an Mt1 overexpressing mouse model (TgMt1). Despite subtle reductions in the expression of neuroinflammatory markers GFAP and IBA1 in the vestibular nucleus and hippocampus, we found no improvement in survival, growth, locomotor activity, balance, or motor coordination in the Mt1 overexpressing Ndufs4-/- mice. Furthermore, at a cellular level, no differences were detected in the metabolomics profile or gene expression of selected one-carbon metabolism and oxidative stress genes, performed in the brain and quadriceps, nor in the ROS levels of macrophages derived from these mice. Considering these outcomes, we conclude that MT1, in general, does not protect against the impaired motor activity or improve survival in these complex I-deficient mice. The unexpected absence of increased oxidative stress and metabolic redox imbalance in this MD model may explain these observations. However, tissue-specific observations such as the mildly reduced inflammation in the hippocampus and vestibular nucleus, as well as differential MT1 expression in these tissues, may yet reveal a tissue- or cell-specific role for MTs in these mice. PMID: 32918239 [PubMed - as supplied by publisher]

Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner. Dis Model Mech. 2020 Sep 11;: Authors: Drews L, Zimmermann M, Westhoff P, Brilhaus D, Poss RE, Bergmann L, Wiek C, Brenneisen P, Piekorz RP, Mettler-Altmann T, Weber APM, Reichert AS Abstract Astrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, within a timescale of minutes mitochondrial respiration and glycolysis were hampered which occurred in a pH-independent manner. Using metabolomics an accumulation of numerous amino acids, including branched chain amino acids and glucose was observed. Metabolomic tracking of 15N-labeled ammonia showed rapid incorporation of 15N into glutamate and glutamate-derived amino acids. Downregulating human GLUD2, encoding mitochondrial glutamate dehydrogenase 2 (GDH2), inhibiting GDH2 activity by SIRT4 overexpression, and supplementing cells with glutamate or glutamine alleviated ammonia-induced inhibition of mitochondrial respiration. Metabolomic tracking of 13C-glutamine showed that hyperammonemia can inhibit anaplerosis of TCA-cycle intermediates. Contrary to its classical anaplerotic role, we show that under hyperammonemia GDH2 rather catalyzes the removal of ammonia by reductive amination of α-ketoglutarate which efficiently and rapidly inhibits the TCA-cycle. Overall, we propose a critical GDH2-dependent mechanism in HE models that on the one hand helps to remove ammonia but on the other hand impairs energy metabolism in mitochondria rapidly. PMID: 32917661 [PubMed - as supplied by publisher]

The use of Lactobacillus plantarum 299v (DSM 9843) in cancer patients receiving home enteral nutrition - study protocol for a randomized, double-blind, and placebo-controlled trial. Nutr J. 2020 Sep 11;19(1):98 Authors: Kaźmierczak-Siedlecka K, Folwarski M, Skonieczna-Żydecka K, Ruszkowski J, Makarewicz W Abstract BACKGROUND: Nutritional treatment is one of the most important components of multidisciplinary anti-cancer therapy. Home enteral nutrition is considered as a safe procedure, however, it may be associated with the risk of side effects, such as nausea, vomiting, abdominal pain, and diarrhoea. It is uncertain whether diarrhoea is the result of the enteral formula administration or gut dysbiosis. One of the methods which may be used to alter the composition of gut microbiota is the administration of a probiotic strain. Lactobacillus plantarum 299v ingestion was found to diminish the adverse events of irritable bowel syndrome and Clostridium difficile infection - entities that share the symptoms with enteral nutrition side effects. Therefore, the primary aim of this study is to determine the effect of Lactobacillus plantarum 299v on prevention of weight loss of cancer patients receiving home enteral nutrition. The secondary aims are to evaluate the role of this probiotic strain in the improvement of nutritional status, enteral nutrition tolerance, and patients' quality of life. METHODS: Forty patients with cancer receiving home enteral nutrition will be enrolled in this clinical trial and randomized to receive one capsule of Lactobacillus plantarum 299v (Sanprobi IBS®) twice a day or placebo for 12 weeks in a double-blind manner. Laboratory tests (the level of albumin, total protein, transferrin, and total lymphocyte count), anthropometric parameters (body mass, the content of fat mass, muscle mass, and total body water), Nutritional Risk Screening (NRS 2002), enteral nutrition tolerance as well as quality of life will be measured. Measurements will be obtained at the baseline and after 4 and 12 weeks of treatment. DISCUSSION: The adverse events observed during administration of enteral nutrition have an negative impact on enteral formula tolerance and as a consequence patients' quality of life. The previous studies have demonstrated that probiotics may reduce the gastrointestinal symptoms related to enteral nutrition. Thus, administration of Lactobacillus plantarum 299v may be effective in improvement of nutritional status, enteral nutrition tolerance, and quality of life of cancer patients receiving home enteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03940768 . PMID: 32917221 [PubMed - as supplied by publisher]

Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) Protocol: A Randomized Clinical Trial. Int J Environ Res Public Health. 2020 Sep 09;17(18): Authors: Kwon S, Riggs J, Crowley G, Lam R, Young IR, Nayar C, Sunseri M, Mikhail M, Ostrofsky D, Veerappan A, Zeig-Owens R, Schwartz T, Colbeth H, Liu M, Pompeii ML, St-Jules D, Prezant DJ, Sevick MA, Nolan A Abstract Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV1). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI). We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. To assess our hypothesis, we developed the Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE), a randomized controlled clinical trial (RCT). Male firefighters with WTC-LI and a BMI > 27 kg/m2 will be included. We will randomize subjects (1:1) to either: (1) Low Calorie Mediterranean (LoCalMed)-an integrative multifactorial, technology-supported approach focused on behavioral modification, nutritional education that will include a self-monitored diet with feedback, physical activity recommendations, and social cognitive theory-based group counseling sessions; or (2) Usual Care. Outcomes include reduction in body mass index (BMI) (primary), improvement in FEV1, fractional exhaled nitric oxide, pulse wave velocity, lipid profiles, targeted metabolic/clinical biomarkers, and quality of life measures (secondary). By implementing a technology-supported LoCalMed diet our FIREHOUSE RCT may help further the treatment of WTC associated pulmonary disease. PMID: 32916985 [PubMed - as supplied by publisher]

Precision Medicine: Steps along the Road to Combat Human Cancer. Cells. 2020 Sep 09;9(9): Authors: Nassar SF, Raddassi K, Ubhi B, Doktorski J, Abulaban A Abstract The diagnosis and treatment of diseases such as cancer is becoming more accurate and specialized with the advent of precision medicine techniques, research and treatments. Reaching down to the cellular and even sub-cellular level, diagnostic tests can pinpoint specific, individual information from each patient, and guide providers to a more accurate plan of treatment. With this advanced knowledge, researchers and providers can better gauge the effectiveness of drugs, radiation, and other therapies, which is bound to lead to a more accurate, if not more positive, prognosis. As precision medicine becomes more established, new techniques, equipment, materials and testing methods will be required. Herein, we will examine the recent innovations in assays, devices and software, along with next generation sequencing in genomics diagnostics which are in use or are being developed for personalized medicine. So as to avoid duplication and produce the fullest possible benefit, all involved must be strongly encouraged to collaborate, across national borders, public and private sectors, science, medicine and academia alike. In this paper we will offer recommendations for tools, research and development, along with ideas for implementation. We plan to begin with discussion of the lessons learned to date, and the current research on pharmacogenomics. Given the steady stream of advances in imaging mass spectrometry and nanoLC-MS/MS, and use of genomic, proteomic and metabolomics biomarkers to distinguish healthy tissue from diseased cells, there is great potential to utilize pharmacogenomics to tailor a drug or drugs to a particular cohort of patients. Such efforts very well may bring increased hope for small groups of non-responders and those who have demonstrated adverse reactions to current treatments. PMID: 32916938 [PubMed - as supplied by publisher]

28 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 2020/09/12PubMed 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.

28 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 2020/09/12PubMed 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.

21 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 2020/09/12PubMed 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.

41 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 2020/09/10PubMed 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.

27 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 2020/09/09PubMed 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.

23 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 2020/09/08PubMed 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.

Related Articles Effects of sulfur fumigation and heating desulfurization on quality of medicinal herbs evaluated by metabolomics and glycomics: Codonopsis Radix, a pilot study. J Pharm Biomed Anal. 2020 Aug 23;191:113581 Authors: Xu F, Kong M, Xu JD, Xu J, Jiang Y, Li SL Abstract Sulfur fumigation and heating desulfurization are used together in the post-harvest processing of many medicinal herbs. However, little is known about the effects of sulfur fumigation on saccharide components, nor about the effects of heating desulfurization on all herbal constituents. In this study, metabolomics and glycomics were integrated to investigate the effects of these two processes on the chemistry of Codonopsis Radix (CR) as a pilot study. The results showed that both sulfur fumigation and heating desulfurization significantly changed the non-saccharide small-molecule metabolome and the glycome of CR in different ways. Chemical mechanisms, such as esterification, glycosidic hydrolysis, esterolysis, amide bond hydrolysis, oxidation and dehydration, are proposed to be involved. These facts strongly inspire that, in addition to investigations of how sulfur fumigation impacts non-saccharide small-molecule metabolites, researches on heating desulfurization and saccharides should be conducted so as to enable accurate, comprehensive evaluation of the quality of sulfur-fumigated herbs. PMID: 32892083 [PubMed - as supplied by publisher]

Related Articles Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults. Environ Int. 2020 Sep 03;145:106091 Authors: Chen Z, Yang T, Walker DI, Thomas DC, Qiu C, Chatzi L, Alderete TL, Kim JS, Conti DV, Breton CV, Liang D, Hauser ER, Jones DP, Gilliland FD Abstract BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) exposure is ubiquitous among the US population and has been linked to adverse health outcomes including cardiometabolic diseases, immune dysregulation and endocrine disruption. However, the metabolic mechanism underlying the adverse health effect of PFASs exposure is unknown. OBJECTIVE: The aim of this project is to investigate the association between PFASs exposure and altered metabolic pathways linked to increased cardiometabolic risk in young adults. METHODS: A total of 102 young adults with 82% overweight or obese participants were enrolled from Southern California between 2014 and 2017. Cardiometabolic outcomes were assessed including oral glucose tolerance test (OGTT) measures, body fat and lipid profiles. High-resolution metabolomics was used to quantify plasma exposure levels of three PFAS congeners and intensity profiles of the untargeted metabolome. Fasting concentrations of 45 targeted metabolites involved in fatty acid and lipid metabolism were used to verify untargeted metabolomics findings. Bayesian Kernel Machine Regression (BKMR) was used to examine the associations between PFAS exposure mixture and cardiometabolic outcomes adjusting for covariates. Mummichog pathway enrichment analysis was used to explore PFAS-associated metabolic pathways. Moreover, the effect of PFAS exposure on the metabolic network, including metabolomic profiles and cardiometabolic outcomes, was investigated. RESULTS: Higher exposure to perfluorooctanoic acid (PFOA) was associated with higher 30-minute glucose levels and glucose area under the curve (AUC) during the OGTT (p < 0.001). PFAS exposure was also associated with altered lipid pathways, which contributed to the metabolic network connecting PFOA and higher glucose levels following the OGTT. Targeted metabolomics analysis indicated that higher PFOA exposure was associated with higher levels of glycerol (p = 0.006), which itself was associated with higher 30-minute glucose (p = 0.006). CONCLUSIONS: Increased lipolysis and fatty acid oxidation could contribute to the biological mechanisms linking PFAS exposure and impaired glucose metabolism among young adults. Findings of this study warrants future experimental studies and epidemiological studies with larger sample size to replicate. PMID: 32892005 [PubMed - as supplied by publisher]