Bile Acids ⇒ 3-oxolithocholic acid {90000282}

Shared Reference Notes

• [1.1] [#Inflamatory bowel disease] 
  - Bile acid > gut-residing bacteria produce metabolite 3-oxolithocholic acid (3-oxoLCA) > inhibits TH17 (inhibitory) cell differentiation. - Secondary bile acid #Lithocholic acid > gut bacteria > 3-oxoLCA as well as the abundant gut metabolite #Isolithocholic acid (isoLCA). - IsoLCA suppressed TH17 differentiation by inhibiting RORγt (retinoic acid receptor-related orphan nuclear receptor γt), a key TH17 cell-promoting transcription factor. - Levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase (3α-HSDH) genes required for their biosynthesis were significantly reduced in patients with inflammatory bowel diseases (IBD). - levels of these #Bile Acids were inversely correlated with expression of TH17 cell-associated genes. - bacterially produced TH17 cell-inhibitory #Bile Acids may reduce the risk of autoimmune and inflammatory disorders such as IBD
• [1.2] [#Isolithocholic acid] 
  - In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages.
• [#Rheumatoid Arthritis] [#Parabacteroides distasonis] - Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. - LPD-derived #Lithocholic acid (LCA), #Deoxycholic acid (DCA), #Isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. - A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids.

References Notes