eprintid: 10104281
rev_number: 24
eprint_status: archive
userid: 608
dir: disk0/10/10/42/81
datestamp: 2020-07-09 07:40:24
lastmod: 2021-09-19 23:16:18
status_changed: 2020-07-09 07:40:24
type: article
metadata_visibility: show
creators_name: Shil, A
creators_name: Olusanya, O
creators_name: Ghufoor, Z
creators_name: Forson, B
creators_name: Marks, J
creators_name: Chichger, H
title: Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G02
keywords: Caco-2, claudin, intestinal epithelium, permeability, sweeteners
note: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
abstract: The breakdown of the intestinal epithelial barrier and subsequent increase in intestinal permeability can lead to systemic inflammatory diseases and multiple-organ failure. Nutrition impacts the intestinal barrier, with dietary components such as gluten increasing permeability. Artificial sweeteners are increasingly consumed by the general public in a range of foods and drinks. The sweet taste receptor (T1R3) is activated by artificial sweeteners and has been identified in the intestine to play a role in incretin release and glucose transport; however, T1R3 has not been previously linked to intestinal permeability. Here, the intestinal epithelial cell line, Caco-2, was used to study the effect of commonly-consumed artificial sweeteners, sucralose, aspartame and saccharin, on permeability. At high concentrations, aspartame and saccharin were found to induce apoptosis and cell death in intestinal epithelial cells, while at low concentrations, sucralose and aspartame increased epithelial barrier permeability and down-regulated claudin 3 at the cell surface. T1R3 knockdown was found to attenuate these effects of artificial sweeteners. Aspartame induced reactive oxygen species (ROS) production to cause permeability and claudin 3 internalization, while sweetener-induced permeability and oxidative stress was rescued by the overexpression of claudin 3. Taken together, our findings demonstrate that the artificial sweeteners sucralose, aspartame, and saccharin exert a range of negative effects on the intestinal epithelium through the sweet taste receptor T1R3.
date: 2020-06-22
date_type: published
official_url: http://dx.doi.org/10.3390/nu12061862
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1794033
doi: 10.3390/nu12061862
pii: nu12061862
lyricists_name: Marks, Joanne
lyricists_id: JMARK89
actors_name: Dewerpe, Marie
actors_id: MDDEW97
actors_role: owner
full_text_status: public
publication: Nutrients
volume: 12
number: 6
article_number: 1862
event_location: Switzerland
citation:        Shil, A;    Olusanya, O;    Ghufoor, Z;    Forson, B;    Marks, J;    Chichger, H;      (2020)    Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3.                   Nutrients , 12  (6)    , Article 1862.  10.3390/nu12061862 <https://doi.org/10.3390/nu12061862>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10104281/9/Marks_Caco2%20sweet%20taste%20paper%20-%20Nutrients%20submitted%20version.pdf