scholarly journals Lipid and Bile Acid Dysmetabolism in Crohn’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Koji Uchiyama ◽  
Hisashi Kishi ◽  
Wataru Komatsu ◽  
Masanori Nagao ◽  
Shuji Ohhira ◽  
...  

Crohn’s disease is one of the systemic autoimmune diseases. It commonly affects the small intestine and colon but may involve any portion of the gastrointestinal tract from the mouth to the anus. The most affected area by Crohn’s disease is the distal part of the small intestine, in which the bile acid molecules are most efficiently reabsorbed. Bile acids form mixed micelles together with fatty acids, which function as a transport vehicle to deliver fatty acids to the apical membrane of enterocytes for absorption. Therefore, if the terminal ileum is impaired, bile acid malabsorption may occur, which may cause congenital diarrhoea in Crohn’s disease. Similarly, the impairment of the terminal ileum also induces fatty acid malabsorption, which may influence the role of fatty acids in Crohn’s disease. In contrast, a recent study reported that multidrug resistance protein 1 (MDR1) regulated effector T-cell function in the ileum from bile acid-driven oxidative stress and MDR1 loss of function in a subset of patients with Crohn’s disease. However, the role of consumption of fatty acids in Crohn’s disease remains to be fully elucidated. This review is aimed at providing an overview of some recent developments in research of Crohn’s disease from comprehensive perspective with a focus on the connection between disease location and behaviour, lipid diets, and bile acid malabsorption.

2018 ◽  
Vol 34 (1) ◽  
pp. 185-188 ◽  
Author(s):  
Thomas Skouras ◽  
Susanna Dodd ◽  
Yash Prasad ◽  
Joseph Rassam ◽  
Nazreen Morley ◽  
...  

1986 ◽  
Vol 21 (5) ◽  
pp. 627-633 ◽  
Author(s):  
L. Tougaard ◽  
B. Giese ◽  
B. Højlund Pedersen ◽  
V. Binder

1994 ◽  
Vol 81 (2) ◽  
pp. 289-290 ◽  
Author(s):  
R. J. Davie ◽  
K. B. Hosie ◽  
S. P. Grobler ◽  
R. A. Newbury-Ecob ◽  
M. R. B. Keighley ◽  
...  

Gut ◽  
1994 ◽  
Vol 35 (1) ◽  
pp. 90-93 ◽  
Author(s):  
H Nyhlin ◽  
M V Merrick ◽  
M A Eastwood

2014 ◽  
Vol 8 ◽  
pp. S177-S178
Author(s):  
A. Ruiz-Cerulla ◽  
F. Rodriguez-Moranta ◽  
L. Rodriguez-Alonso ◽  
C. Àrajol ◽  
T. Lobatón Ortega ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Iris Stolzer ◽  
Anja Dressel ◽  
Mircea T. Chiriac ◽  
Markus F. Neurath ◽  
Claudia Günther

Blocking interferon-function by therapeutic intervention of the JAK-STAT-axis is a novel promising treatment option for inflammatory bowel disease (IBD). Although JAK inhibitors have proven efficacy in patients with active ulcerative colitis (UC), they failed to induce clinical remission in patients with Crohn's disease (CD). This finding strongly implicates a differential contribution of JAK signaling in both entities. Here, we dissected the contribution of different STAT members downstream of JAK to inflammation and barrier dysfunction in a mouse model of Crohn's disease like ileitis and colitis (Casp8ΔIEC mice). Deletion of STAT1 in Casp8ΔIEC mice was associated with reduced cell death and a partial rescue of Paneth cell function in the small intestine. Likewise, organoids derived from the small intestine of these mice were less sensitive to cell death triggered by IBD-key cytokines such as TNFα or IFNs. Further functional in vitro and in vivo analyses revealed the impairment of MLKL-mediated necrosis as a result of deficient STAT1 function, which was in turn associated with improved cell survival. However, a decrease in inflammatory cell death was still associated with mild inflammation in the small intestine. The impact of STAT1 signaling on gastrointestinal inflammation dependent on the localization of inflammation, as STAT1 is essential for intestinal epithelial cell death regulation in the small intestine, whereas it is not the key factor for intestinal epithelial cell death in the context of colitis. Of note, additional deletion of STAT2 was not sufficient to restore Paneth cell function but strongly ameliorated ileitis. In summary, we provide here compelling molecular evidence that STAT1 and STAT2, both contribute to intestinal homeostasis, but have non-redundant functions. Our results further demonstrate that STATs individually affect the distinct pathophysiology of inflammation in the ileum and colon, respectively, which might explain the diverse outcome of JAK inhibitors on inflammatory bowel diseases.


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