scholarly journals The Human Fecal Microbiota Metabolizes Deoxynivalenol and Deoxynivalenol-3-Glucoside and May Be Responsible for Urinary Deepoxy-Deoxynivalenol

2013 ◽  
Vol 79 (6) ◽  
pp. 1821-1825 ◽  
Author(s):  
Silvia W. Gratz ◽  
Gary Duncan ◽  
Anthony J. Richardson
Keyword(s):  
Intestinal Bacteria ◽  
Potential Effect ◽  
Fecal Microbiota ◽  
Farm Animals ◽  
Toxic Metabolite ◽  
Content Type ◽  
Human Intestinal Bacteria ◽  
Liquid Chromatography Tandem Mass ◽  
Plant Metabolite

ABSTRACTDeoxynivalenol (DON) is a potent mycotoxin produced byFusariummolds and affects intestinal nutrient absorption and barrier function in experimental and farm animals. Free DON and the plant metabolite DON-3-β-d-glucoside (D3G) are frequently found in wheat and maize. D3G is stable in the upper human gut, but some human intestinal bacteria release DON from D3Gin vitro. Furthermore, some bacteria derived from animal digestive systems degrade DON to a less toxic metabolite, deepoxy-deoxynivalenol (DOM-1). The metabolism of D3G and DON by the human microbiota has not been fully assessed. We therefore conductedin vitrobatch culture experiments assessing the activity of the human fecal microbiota to release DON from D3G. We also studied detoxification of DON to DOM-1 by the microbiota and its potential effect on urinary DON excretion in humans. Fecal slurry from five volunteers was spiked with DON or D3G and incubated anaerobically (from 1 h to 7 days), and mycotoxins were extracted into acetonitrile. Mycotoxins were detected in fecal extracts and urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The fecal microbiota released DON from D3G very efficiently, with hydrolysis peaking after 4 to 6 h. The fecal microbiota from one volunteer transformed DON to DOM-1. Urine from the same volunteer also contained DOM-1 (4.7% of DON), whereas DOM-1 was not detectable in urine from other volunteers. Our results confirm that the fecal microbiota releases DON from its glycosylated form, hence increasing the toxic burden in exposed individuals. Furthermore, this is first evidence that the human fecal microbiota of one volunteer detoxifies DON, resulting in the appearance of DOM-1 in urine.

scholarly journals Bacillus cereus NVH 0500/00 Can Adhere to Mucin but Cannot Produce Enterotoxins during Gastrointestinal Simulation

2015 ◽  
Vol 82 (1) ◽  
pp. 289-296 ◽  
Author(s):  
Varvara Tsilia ◽  
Frederiek-Maarten Kerckhof ◽  
Andreja Rajkovic ◽  
Marc Heyndrickx ◽  
Tom Van de Wiele
Keyword(s):  
Bacillus Cereus ◽  
Food Poisoning ◽  
Intestinal Bacteria ◽  
Low Ph ◽  
Final Concentration ◽  
Adhesion Assay ◽  
Content Type ◽  
The Stability ◽  
Bacterial Concentrations

ABSTRACTAdhesion to the intestinal epithelium could constitute an essential mechanism ofBacillus cereuspathogenesis. However, the enterocytes are protected by mucus, a secretion composed mainly of mucin glycoproteins. These may serve as nutrients and sites of adhesion for intestinal bacteria. In this study, the food poisoning bacteriumB. cereusNVH 0500/00 was exposedin vitroto gastrointestinal hurdles prior to evaluation of its attachment to mucin microcosms and its ability to produce nonhemolytic enterotoxin (Nhe). The persistence of mucin-adherentB. cereusafter simulated gut emptying was determined using a mucin adhesion assay. The stability of Nhe toward bile and pancreatin (intestinal components) in the presence of mucin agar was also investigated.B. cereuscould grow and simultaneously adhere to mucin duringin vitroileal incubation, despite the adverse effect of prior exposure to a low pH or intestinal components. The final concentration ofB. cereusin the simulated lumen at 8 h of incubation was 6.62 ± 0.87 log CFU ml−1. At that point, the percentage of adhesion was approximately 6%. No enterotoxin was detected in the ileum, due to either insufficient bacterial concentrations or Nhe degradation. Nevertheless, mucin appears to retainB. cereusand to supply it to the small intestine after simulated gut emptying. Additionally, mucin may play a role in the protection of enterotoxins from degradation by intestinal components.

scholarly journals Asymmetric Arginine Dimethylation Modulates Mitochondrial Energy Metabolism and Homeostasis in Caenorhabditis elegans

2016 ◽  
Vol 37 (6) ◽  
Author(s):  
Liang Sha ◽  
Hiroaki Daitoku ◽  
Sho Araoi ◽  
Yuta Kaneko ◽  
Yuta Takahashi ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Mitochondrial Function ◽  
Atp Synthesis ◽  
Subcellular Fractionation ◽  
Mitochondrial Energy Metabolism ◽  
Content Type ◽  
Liquid Chromatography Tandem Mass ◽  
Protein Arginine Methyltransferase 1

ABSTRACT Protein arginine methyltransferase 1 (PRMT-1) catalyzes asymmetric arginine dimethylation on cellular proteins and modulates various aspects of biological processes, such as signal transduction, DNA repair, and transcriptional regulation. We have previously reported that the null mutant of prmt-1 in Caenorhabditis elegans exhibits a slightly shortened life span, but the physiological significance of PRMT-1 remains largely unclear. Here we explored the role of PRMT-1 in mitochondrial function as hinted by a two-dimensional Western blot-based proteomic study. Subcellular fractionation followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that PRMT-1 is almost entirely responsible for asymmetric arginine dimethylation on mitochondrial proteins. Importantly, isolated mitochondria from prmt-1 mutants represent compromised ATP synthesis in vitro, and whole-worm respiration in prmt-1 mutants is decreased in vivo. Transgenic rescue experiments demonstrate that PRMT-1-dependent asymmetric arginine dimethylation is required to prevent mitochondrial reactive oxygen species (ROS) production, which consequently causes the activation of the mitochondrial unfolded-protein response. Furthermore, the loss of enzymatic activity of prmt-1 induces food avoidance behavior due to mitochondrial dysfunction, but treatment with the antioxidant N-acetylcysteine significantly ameliorates this phenotype. These findings add a new layer of complexity to the posttranslational regulation of mitochondrial function and provide clues for understanding the physiological roles of PRMT-1 in multicellular organisms.

scholarly journals In Vitro Human Onychopharmacokinetic and Pharmacodynamic Analyses of ME1111, a New Topical Agent for Onychomycosis

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Natsuki Kubota-Ishida ◽  
Naomi Takei-Masuda ◽  
Kaori Kaneda ◽  
Yu Nagira ◽  
Tsubasa Chikada ◽  
...  
Keyword(s):  
Antifungal Agent ◽  
Antifungal Agents ◽  
Nail Plate ◽  
Free Drug ◽  
Content Type ◽  
Clinical Dose ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
Human Nails

ABSTRACT ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in the application of topical onychomycotics is penetration and dissemination of antifungal agent into the infected nail plate and bed. In this study, pharmacokinetic/pharmacodynamic parameters of ME1111 that potentially correlate with clinical efficacy were compared with those of marketed topical onychomycosis antifungal agents: efinaconazole, tavaborole, ciclopirox, and amorolfine. An ME1111 solution and other launched topical formulations were applied to an in vitro dose model for 14 days based on their clinical dose and administration. Drug concentrations in the deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-tandem mass spectrometry. Concentrations of ME1111 in the nail and cotton pads were much higher than those of efinaconazole, ciclopirox, and amorolfine. Free drug concentrations of ME1111 in deep nail layers and cotton pads were orders of magnitude higher than the MIC90 value against Trichophyton rubrum (n = 30). Unlike other drugs, the in vitro antifungal activity of ME1111 was not affected by 5% human keratin and under a mild acidic condition (pH 5.0). The in vitro antidermatophytic efficacy coefficients (ratio of free drug concentration to MIC90s against T. rubrum) of ME1111, as measured in deep nail layers, were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine (P < 0.05). This suggests that ME1111 has excellent permeation of human nails and, consequently, the potential to be an effective topical onychomycosis treatment.

scholarly journals Digestion and fermentation by human intestinal bacteria of corn fiber and its hemicellulose in vitro.

1991 ◽  
Vol 55 (2) ◽  
pp. 565-567 ◽  
Author(s):  
Masayoshi SUGAWARA ◽  
Yoshimi BENNO ◽  
Emiko KOYASU ◽  
Masayasu TAKEUCHI ◽  
Tomotari MITSUOKA
Keyword(s):  
Intestinal Bacteria ◽  
Corn Fiber ◽  
Human Intestinal Bacteria

scholarly journals Cinnamaldehyde Induces Expression of Efflux Pumps and Multidrug Resistance in Pseudomonas aeruginosa

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Alexandre Tetard ◽  
Andy Zedet ◽  
Corine Girard ◽  
Patrick Plésiat ◽  
Catherine Llanes
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Content Adaptation ◽  
Toxic Metabolite ◽  
Regulatory Pathway ◽  
Content Type ◽  
Antagonistic Effects ◽  
Cinnamon Bark ◽  
Therapeutic Consequences

ABSTRACT Essential oils or their components are increasingly used to fight bacterial infections. Cinnamaldehyde (CNA), the main constituent of cinnamon bark oil, has demonstrated interesting properties in vitro against various pathogens, including Pseudomonas aeruginosa. In the present study, we investigated the mechanisms and possible therapeutic consequences of P. aeruginosa adaptation to CNA. Exposure of P. aeruginosa PA14 to subinhibitory concentrations of CNA caused a strong albeit transient increase in the expression of operons that encode the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY/OprM. This multipump activation enhanced from 2- to 8-fold the resistance (MIC) of PA14 to various antipseudomonal antibiotics, including meropenem, ceftazidime, tobramycin, and ciprofloxacin. CNA-induced production of pump MexAB-OprM was found to play a major role in the adaption of P. aeruginosa to the electrophilic biocide, through the NalC regulatory pathway. CNA was progressively transformed by bacteria into the less toxic metabolite cinnamic alcohol (CN-OH), via yet undetermined detoxifying mechanisms. In conclusion, the use of cinnamon bark oil or cinnamaldehyde as adjunctive therapy to treat P. aeruginosa infections may potentially have antagonistic effects if combined with antibiotics because of Mex pump activation.

scholarly journals Contribution of gut bacteria to the metabolism of cyanidin 3-glucoside in human microbiota-associated rats

2012 ◽  
Vol 109 (8) ◽  
pp. 1433-1441 ◽  
Author(s):  
Laura Hanske ◽  
Wolfram Engst ◽  
Gunnar Loh ◽  
Silke Sczesny ◽  
Michael Blaut ◽  
...  
Keyword(s):  
Intestinal Bacteria ◽  
Hydroxycinnamic Acid ◽  
Gut Bacteria ◽  
Dihydroxybenzoic Acid ◽  
Human Gut ◽  
Germ Free ◽  
Human Microbiota ◽  
Human Intestinal Bacteria ◽  
The Impact

Cyanidin 3-glucoside (C3G) is one of the major dietary anthocyanins implicated in the prevention of chronic diseases. To evaluate the impact of human intestinal bacteria on the fate of C3G in the host, we studied the metabolism of C3G in human microbiota-associated (HMA) rats in comparison with germ-free (GF) rats. Urine and faeces of the rats were analysed for C3G and its metabolites within 48 h after the application of 92 μmol C3G/kg body weight. In addition, we tested the microbial C3G conversion in vitro by incubating C3G with human faecal slurries and selected human gut bacteria. The HMA rats excreted with faeces a three times higher percentage of unconjugated C3G products and a two times higher percentage of conjugated C3G products than the GF rats. These differences were mainly due to the increased excretion of 3,4-dihydroxybenzoic acid, 2,4,6-trihydroxybenzaldehyde and 2,4,6-trihydroxybenzoic acid. Only the urine of HMA rats contained peonidin and 3-hydroxycinnamic acid and the percentage of conjugated C3G products in the urine was decreased compared with the GF rats. Overall, the presence of intestinal microbiota resulted in a 3·7 % recovery of the C3G dose in HMA rats compared with 1·7 % in GF rats. Human intestinal bacteria rapidly degraded C3G in vitro. Most of the C3G products were also found in the absence of bacteria, but at considerably lower levels. The higher concentrations of phenolic acids observed in the presence of intestinal bacteria may contribute to the proposed beneficial health effects of C3G.

Toxicity of Graphene Oxide on Intestinal Bacteria and Caco-2 Cells

2015 ◽  
Vol 78 (5) ◽  
pp. 996-1002 ◽  
Author(s):  
TRANG H. D. NGUYEN ◽  
MENGSHI LIN ◽  
AZLIN MUSTAPHA
Keyword(s):  
Graphene Oxide ◽  
Food Packaging ◽  
Antibacterial Properties ◽  
Intestinal Bacteria ◽  
Cytotoxic Action ◽  
Human Intestinal Bacteria ◽  
Potential Applications ◽  
Weak Adsorption ◽  
Agriculture And Food

In recent years, novel nanomaterials have received much attention due to their great potential for applications in agriculture, food safety, and food packaging. Among them, graphene and graphene oxide (GO) are emerging as promising nanomaterials that may have a profound impact on food packaging. However, there are some concerns from consumers and the scientific community about the potential toxicity and biocompatibility of nanomaterials. In this study, we investigated the antibacterial properties of GO against human intestinal bacteria. The cytotoxicity of GO was also studied in vitro using the Caco-2 cell line derived from a colon carcinoma. Electron microscopy was used to investigate the morphology of GO and the interaction between GO flakes and Caco-2 cells. GO at different concentrations (10 to 500 μg/ml) exhibited no toxicity against the selected bacteria and a mild cytotoxic action on Caco-2 cells after 24 h of exposure. The results show that weak adsorption of medium nutrients may contribute to GO's low toxicity. This study suggests that GO is biocompatible and has a potential to be used in agriculture and food science, indicating that more studies are needed to exploit its potential applications.

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