Imperial College London

Emeritus ProfessorJeremyNicholson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@misc{McArthur:2017,
author = {McArthur, S and Umlai, UK and Snelling, T and Nicholson, JK and Carding, SR and Glen, RC and Hoyles, L},
title = {Effects of gut-derived methylamines on the blood–brain barrier},
type = {Poster},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - GEN
AB - Introduction: Composition and functions of the gut microbiota are inextricably linked with host health, and altered in conditions such as obesity and type II diabetes. Central to microbe–host crosstalk are gut-derived microbial metabolites, of which trimethylamine N-oxide (TMAO) and its precursor trimethylamine (TMA) are of particular importance. TMA produced by intestinal microbes is converted to TMAO in the liver by flavin monooxygenases with circulating TMAO being associated with cardiovascular disease and insulin resistance. TMAO was also recently identified as potentially important in genetic pathways associated with Alzheimer’s disease (AD). In considering that deficits in blood–brain barrier (BBB) function occur early in AD, and its position as the major interface between circulating metabolites and the brain, we investigated the effects of TMAO and TMA on key BBB properties in vitro.Materials and Methods: Human hCMEC/D3 cerebromicrovascular cells were used as an in vitro model of the BBB to investigate the effects of 24 h treatment with physiologically relevant doses of TMAO and TMA, studying (i) functional barrier properties of cell monolayers, (ii) Aβ efflux transporters and (iii) gene expression.Results: Exposure of hCMEC/D3 cells to TMAO (40 μM) reinforced barrier integrity by enhancing transendothelial electrical resistance (P <0.001) and reducing paracellular permeability to a 70 kDa dextran tracer (P <0.001). In contrast, while TMA (0.4 μM) enhanced electrical resistance (P <0.001), it significantly increased tracer paracellular permeability (P <0.05), consistent with compromised barrier function. Transporter activity analysis showed TMAO inhibited p-glycoprotein function (P <0.001), which was not seen with TMA; neither metabolite affected BCRP function. Human-genome transcriptomic data are currently being analysed.Conclusions: TMAO and TMA affect BBB function in a metabolite-specific manner, regulating barr
AU - McArthur,S
AU - Umlai,UK
AU - Snelling,T
AU - Nicholson,JK
AU - Carding,SR
AU - Glen,RC
AU - Hoyles,L
PY - 2017///
TI - Effects of gut-derived methylamines on the blood–brain barrier
ER -