Author(s): Gaifem, Joana ; Gonçalves, Luís G. ; Dinis-Oliveira, Ricardo J. ; Cunha, Cristina ; Carvalho, Agostinho ; Torrado, Egídio ; Rodrigues, Fernando José dos Santos ; Saraiva, Margarida ; Castro, António G. ; Silvestre, Ricardo Jorge Leal
Date: 2018
Persistent ID: http://hdl.handle.net/1822/58050
Origin: RepositóriUM - Universidade do Minho
Subject(s): IBD; Threonine; DSS-induced colitis; Goblet cells; Metabolomics; IL-22; Mucin; Science & Technology; Ciências Médicas::Medicina Básica
Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory bowel disease (IBD) given their impact on intestinal homeostasis through the modulation of immune response, gut microbiota composition and epithelial barrier stability. Several nutrients have already been associated with a protective phenotype. Yet, there is a lack of knowledge toward the most promising ones as well as the most adequate phase of action. To unveil the most prominent therapy candidates we characterized the colon metabolic profile during colitis development. We have observed a twofold decrease in threonine levels in mice subjected to DSS-induced colitis. We then assessed the effect of threonine supplementation in the beginning of the inflammatory process (DSS + Thr) or when inflammation is already established (DSS + Thr D8). Colitis progression was similar between the treated groups and control colitic mice, yet threonine had a surprisingly detrimental effect when administered in the beginning of the disease, with mice displaying a delayed recovery when compared to control mice and mice supplemented with threonine after day 8. Although no major changes were found in their metabolic profile, DSS + Thr mice displayed altered expression in mucin-encoding genes, as well as in goblet cell counts, unveiling an impaired ability to produce mucus. Moreover, IL-22 secretion was decreased in DSS + Thr mice when compared to DSS + Thr D8 mice. Overall, these results suggest that supplementation with threonine during colitis induction impact goblet cell number and delays the recovery period. This reinforces the importance of a deeper understanding regarding threonine supplementation in IBD.
Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013) and the Fundação para a Ciência e Tecnologia (FCT) (contracts PD/BD/106053/2015 to JG via Inter-University Doctoral Programme in Ageing and Chronic Disease – PhDOC, IF/00021/2014 to RS, IF/01390/2014 to ET, IF/01147/2013 to RD-O, IF/00735/2014 to AgC, SFRH/BPD/96176/2013 to CC, and SFRH/BPD/111100/2015 to LG). MS is a FCT investigator. The NMR data was acquired at CERMAX (Centro de Ressonância Magnética António Xavier) which is a member of the National NMR network with the support of Project LISBOA-01-0145-FEDER-007660
info:eu-repo/semantics/publishedVersion
