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https://www.readbyqxmd.com/read/28520899/increased-urinary-trimethylamine-n-oxide-tmao-following-cryptosporidium-infection-and-protein-malnutrition-independent-of-microbiome-effects
#1
D T Bolick, J Mayneris-Perxachs, G L Medlock, G L Kolling, J Papin, J R Swann, R L Guerrant
Cryptosporidium infections have been associated with growth stunting even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared to uninfected controls. Following infection there was an increase in the urinary excretion of choline- and amino acid-derived metabolites...
May 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28515319/the-h-region-of-twin-arginine-signal-peptides-supports-productive-binding-of-bacterial-tat-precursor-proteins-to-the-tatbc-receptor-complex
#2
Agnes Ulfig, Julia Fröbel, Frank Lausberg, Anne-Sophie Blümmel, Anna Katharina Heide, Matthias Müller, Roland Freudl
The twin arginine translocation (Tat) pathway transports folded proteins across bacterial membranes. Tat precursor proteins possess a conserved twin-arginine (RR) motif in their signal peptides that is involved in their binding to the Tat translocase, but some facets of this interaction remain unclear. Here, we investigated the role of the hydrophobic (h-) region of the Escherichia coli TMAO reductase (TorA) signal peptide in TatBC receptor binding in vivo and in vitro. We show that besides the RR motif, a minimal functional h-region in the signal peptide is required for Tat-dependent export in E...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511293/enterobacter-aerogenes-zdy01-attenuates-choline-induced-trimethylamine-n-oxide-levels-via-remodeling-gut-microbiota-in-mice
#3
Liang Qiu, Dong Yang, Xueying Tao, Jun Yu, Hua Xiong, Hua Wei
Trimethylamine N-oxide (TMAO), which is transformed from trimethylamine (TMA) through hepatic flavin-containing monooxygenases, can promote atherosclerosis. TMA is produced from dietary carnitine, phosphatidylcholine, and choline via the gut microbes. Previous works have shown that some small molecules, such as allicin, resveratrol, and 3,3-dimethyl-1-butanol, are used to reduce circulating TMAO levels. However, the use of bacteria as an effective therapy to reduce TMAO levels has not been reported. In the present study, 82 isolates were screened from healthy Chinese fecal samples on a basal salt medium supplemented with TMA as sole carbon source...
May 17, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28498348/nutrients-turned-into-toxins-microbiota-modulation-of-nutrient-properties-in-chronic-kidney-disease
#4
REVIEW
Raul Fernandez-Prado, Raquel Esteras, Maria Vanessa Perez-Gomez, Carolina Gracia-Iguacel, Emilio Gonzalez-Parra, Ana B Sanz, Alberto Ortiz, Maria Dolores Sanchez-Niño
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects...
May 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28479364/involvement-of-organic-cation-transporters-in-the-kinetics-of-trimethylamine-n-oxide
#5
Takeshi Miyake, Tadahaya Mizuno, Tatsuki Mochizuki, Miyuki Kimura, Shunji Matsuki, Shin Irie, Ichiro Ieiri, Maeda Kazuya, Hiroyuki Kusuhara
Recent studies suggest that trimethylamine N-oxide (TMAO) is associated with the development of chronic kidney disease and heart failure. In this study, we investigated the importance of organic cation transporters (OCTs) in the clearance and tissue distribution of TMAO. The low affinity and high capacity transport of TMAO by mouse and human OCT1 and OCT2 was observed. Uptake and efflux of TMAO by the mouse hepatocytes as well as TMAO uptake into mouse kidney slices were significantly decreased by the addition of tetraethylammonium or Oct1/2 double knockout (dKO)...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28469156/impaired-renal-function-and-dysbiosis-of-gut-microbiota-contribute-to-increased-trimethylamine-n-oxide-in-chronic-kidney-disease-patients
#6
Kai-Yu Xu, Geng-Hong Xia, Jun-Qi Lu, Mu-Xuan Chen, Xin Zhen, Shan Wang, Chao You, Jing Nie, Hong-Wei Zhou, Jia Yin
Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28447688/influence-of-cosolvents-self-crowding-temperature-and-pressure-on-the-sub-nanosecond-dynamics-and-folding-stability-of-lysozyme
#7
S R Al-Ayoubi, P H Schummel, M Golub, J Peters, R Winter
We studied the effects of temperature and hydrostatic pressure on the dynamical properties and folding stability of highly concentrated lysozyme solutions in the absence and presence of the osmolytes trimethylamine-N-oxide (TMAO) and urea. Elastic incoherent neutron scattering (EINS) was applied to determine the mean-squared displacement (MSD) of the protein's hydrogen atoms to yield insights into the effects of these cosolvents on the averaged sub-nanosecond dynamics in the pressure range from ambient up to 4000 bar...
April 27, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28447460/effects-of-histidine-supplementation-on-global-serum-and-urine-1-h-nmr-based-metabolomics-and-serum-amino-acid-profiles-in-obese-women-from-a-randomized-controlled-study
#8
Shanshan Du, Shuhong Sun, Liyan Liu, Qiao Zhang, Fuchuan Guo, Chunlong Li, Rennan Feng, Changhao Sun
The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine (1)H NMR-based metabolomics and serum AA profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum (1)H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/β-glucose were exhibited after histidine supplement...
May 5, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28439531/genome-and-cd4-t-cell-methylome-wide-association-study-of-circulating-trimethylamine-n-oxide-in-the-genetics-of-lipid-lowering-drugs-and-diet-network-goldn
#9
Stella Aslibekyan, Marguerite R Irvin, Bertha A Hidalgo, Rodney T Perry, Elias J Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N Hopkins, Michael A Province, Hemant K Tiwari, Jose M Ordovas, Devin M Absher, Donna K Arnett
BACKGROUND: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels. METHODS AND RESULTS: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans...
June 2017: Journal of Nutrition & Intermediary Metabolism
https://www.readbyqxmd.com/read/28434257/ratio-of-serum-levels-of-ages-to-soluble-rage-is-correlated-with-trimethylamine-n-oxide-in-non-diabetic-subjects
#10
Atsuko Tahara, Nobuhiro Tahara, Sho-Ichi Yamagishi, Akihiro Honda, Sachiyo Igata, Yoshikazu Nitta, Munehisa Bekki, Tomohisa Nakamura, Yoichi Sugiyama, Jiahui Sun, Masayoshi Takeuchi, Makiko Shimizu, Hiroshi Yamazaki, Kei Fukami, Yoshihiro Fukumoto
Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear...
April 23, 2017: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/28433924/the-metabolic-fate-of-isotopically-labeled-trimethylamine-n-oxide-tmao-in-humans
#11
Siraphat Taesuwan, Clara E Cho, Olga V Malysheva, Erica Bender, Julia H King, Jian Yan, Anna E Thalacker-Mercer, Marie A Caudill
Trimethylamine-N-oxide (TMAO) is associated with chronic disease risk. However, little is known about the metabolic fate of dietary TMAO. This study sought to quantitatively elucidate the metabolic fate of orally consumed TMAO in humans. As part of a crossover feeding study, healthy young men (n=40) consumed 50-mg deuterium-labeled methyl d9-TMAO (d9-TMAO), and enrichments of TMAO and its derivatives were measured in blood for 6 h, urine and stool, as well as skeletal muscle in a subset of men (n=6). Plasma d9-TMAO was detected as early as 15 min, increased until 1 h and remained elevated through the 6-h period...
April 13, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28432876/effect-of-pistachio-consumption-on-the-modulation-of-urinary-gut-microbiota-related-metabolites-in-prediabetic-subjects
#12
Pablo Hernández-Alonso, Daniel Cañueto, Simona Giardina, Jordi Salas-Salvadó, Nicolau Cañellas, Xavier Correig, Mònica Bulló
The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out...
April 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28407784/relationships-between-gut-microbiota-plasma-metabolites-and-metabolic-syndrome-traits-in-the-metsim-cohort
#13
Elin Org, Yuna Blum, Silva Kasela, Margarete Mehrabian, Johanna Kuusisto, Antti J Kangas, Pasi Soininen, Zeneng Wang, Mika Ala-Korpela, Stanley L Hazen, Markku Laakso, Aldons J Lusis
BACKGROUND: The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. RESULTS: We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose...
April 13, 2017: Genome Biology
https://www.readbyqxmd.com/read/28389555/targeting-of-microbe-derived-metabolites-to-improve-human-health-the-next-frontier-for-drug-discovery
#14
J Mark Brown, Stanley L Hazen
Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) has been causally linked to the development of cardiovascular diseases...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28378399/osmolyte-effects-on-the-conformational-dynamics-of-a-dna-hairpin-at-ambient-and-extreme-environmental-conditions
#15
Satyajit Patra, Christian Anders, Nelli Erwin, Roland Winter
The structural dynamics of a DNA hairpin (Hp) are studied in the absence and presence of the two natural osmolytes trimethylamine-N-oxide (TMAO) and urea at ambient and extreme environmental conditions, including high pressures and high temperatures, by using single-molecule Förster resonance energy transfer and fluorescence correlation spectroscopy. The effect of pressure on the conformational dynamics of the DNA Hp is investigated on a single-molecule level, providing novel mechanistic insights into its conformational conversions...
April 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28377725/gut-microbiota-dependent-metabolite-trimethylamine-n-oxide-contributes-to-cardiac-dysfunction-in-western-diet-induced-obese-mice
#16
Kui Chen, Xiaoqian Zheng, Mingchen Feng, Dongliang Li, Hongqi Zhang
Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28377341/-a-machine-learning-model-using-gut-microbiome-data-for-predicting-changes-of-trimethylamine-n-oxide-in-healthy-volunteers-after-choline-consumption
#17
Jun-Qi Lu, Shan Wang, Jia Yin, Shan Wu, Yan He, Hui-Min Zheng, Hua-Fang Sheng, Hong-Wei Zhou
OBJECTIVE: To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease. METHODS: We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge...
March 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28356058/hiv-infected-persons-with-type-2-diabetes-show-evidence-of-endothelial-dysfunction-and-increased-inflammation
#18
Malene Hove-Skovsgaard, Julie Christine Gaardbo, Lilian Kolte, Kamilla Winding, Ingebjørg Seljeflot, Asbjørn Svardal, Rolf Kristian Berge, Jan Gerstoft, Henrik Ullum, Marius Trøseid, Susanne Dam Nielsen
BACKGROUND: Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. METHODS: Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-))...
March 29, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28301576/restored-mutant-receptor-corticoid-binding-in-chaperone-complexes-by-trimethylamine-n-oxide
#19
Aaron L Miller, W Austin Elam, Betty H Johnson, Shagufta H Khan, Raj Kumar, E Brad Thompson
Without a glucocorticoid (GC) ligand, the transcription factor glucocorticoid receptor (GR) is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide (TMAO), on a conditions-dependent "activation-labile" mutant GR (GRact/l), which under GR-activating conditions cannot bind GCs in cells or in cell cytosols...
2017: PloS One
https://www.readbyqxmd.com/read/28293920/the-intriguing-link-between-the-intestinal-microbiota-and-cardiovascular-disease
#20
Giuseppe Lippi, Elisa Danese, Camilla Mattiuzzi, Emmanuel J Favaloro
Human microbiota is a term conventionally used to define the normal flora of microbes living in all of us, most of which are resident in the gastrointestinal tract. Despite it having been known for some time that the vast majority of intestinal bacteria exert a strong influence on human life, recent technologic breakthroughs have made it possible to more accurately characterize the host microbial communities and explore their relationship with many human diseases. Notably, the evidence accumulated over the past 10 years suggests that a reasonable relationship can now be established between gut microbiota composition and the risk of cardiovascular disease...
March 14, 2017: Seminars in Thrombosis and Hemostasis
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