Lithocholic acid {90000159}

Shared Reference Notes

• [1.1] 
  - Lithocholic acid can inhibit #Breast cancer progression, epithelial-mesenchymal transition, and metastasis via activation of nuclear factor erythroid 2-related factor 2 (NRF2) and other proteins involved in the antioxidant defense system.
• [1.2] [#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
• [1.3] [#Bile Acids] 
  - Butyrate producing bacteria such as #Eubacterium spp. are capable of transforming primary BAs to secondary BAs such as: lithocholic acid and #Deoxycholic acid, which are potentially cytotoxic and have been linked to #Colorectal cancer and cholesterol GS formation.
• [1.4] [#Primary bile acids, #Secondary bile acids] 
  - Primary #Bile Acids are conjugated in several different forms and secreted into the intestine. - a small portion (~5%) of the Primary #Bile Acids (about 200 to 800 mg daily in humans) escapes the reabsorption in Ileum and reaches the colon where gut bacteria convert them into secondary #Bile Acids (SBAs), such as #Deoxycholic acid (DCA), #Ursodeoxycholic acid (UDCA), and lithocholic acid (LCA). - majority (90% to 95%) of SBAs are reabsorbed into colonocytes to return to the liver for detoxification and recycling.
• [1.5] 
  - higher concentrations of #Deoxycholic acid (DCA), lithocholic acid (LCA), and #Cholic acid (CA) in feces in #Stroke patients are associated with higher survival after #Stroke.
• [1.6] [#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.
• [1.7] 
  - #Walnut consumption also decreased pro-inflammatory #Bile Acids #Deoxycholic acid and lithocholic acid and serum LDL #Cholesterol
• [1.8] [#Parkinson’s Disease] [#Alpha-synuclein] 
  - The increases of #Deoxycholic acid and lithocholic acid can propel the accumulation of pathological α-synuclein aggregates, which can potentially propagate from the gut to the brain through retrograde transport
• [#Parkinson’s Disease] [#Alpha-synuclein] - #Ursodeoxycholic acid is another secondary bile acid that has neuroprotective effects an can prevent the damaging effects of #Deoxycholic acid and lithocholic acid. - In a chronic PD mouse model, pretreatment with tauroursodeoxycholic acid can protect against dopaminergic neuronal damage, prevent microglial and astroglial activation, as well as the dopamine and 3-4-dihydroxyphenulacetic acid reductions caused by MPTP. - Pretreatment with tauroursodeoxycholic acid can prevent protein oxidation and autophagy, in addition to inhibiting α-synuclein aggregation
• [#Parkinson’s Disease] - microbially derived toxic #Bile Acids such as #Deoxycholic acid and lithocholic acid are heightened in PD
• [1.9] [#Cancer] [#Bile Acids, #Deoxycholic acid] 
  - Secondary BA, DCA, and LCA can cause DNA damage
• [#Eggerthella lenta] [#Bile Acids, #Deoxycholic acid] - E. lenta gavage also altered BA metabolism as observed by increased primary and secondary BA including DCA and lithocholate (LCA)
• [#Diabetes Type 1] [#Bile Acids] - administration of secondary BAs, specifically LCA, a secondary BA, causes downregulation of circulating lipids, similar to previous findings in progression to T1D. - two distinct derivatives of LCA, including 3-oxoLCA and isoallo LCA, were found to affect host immune responses by directly modulating T cell differentiation, potentially via gut microbial activity.
• [1.11] [#Inflamatory bowel disease] [#Ruminococcus gnavus] 
  - R. gnavus has also been reported as a producer of #Ursodeoxycholic acid (UDCA) > It possesses an enzyme that can degrade 7-keto lithocholic acid (LCA) into UDCA. - Administration of UDCA has been shown to increase colonic LCA levels and inhibit caspase-3 cleavage. - Abnormal apoptosis in intestinal epithelial cells (IECs) can disrupt the integrity of the intestinal barrier, leading to bacterial infiltration and triggering an inflammatory cascade.
• [1.12] [#Crohn’s disease] [#Bile Acids, #Deoxycholic acid] 
  - Individuals with CD had lower plasma concentrations of the majority of secondary BA compared to controls, in total CD/CC ratio 0.60. - The most prominent observations were lower levels of deoxycolic acid derivates and lithocolic acid derivates among participants with CD. - plasma concentration for secondary BA among participants with active CD was significantly lower compared to those with CD in remission, CD active/CD remission ratio 0.65
• [1.13] [#GLP-1] 
  - Lithocholic acid increases glucagon-like peptide-1 secretion in NCI-H716 cells.
• - combination of lithocholic acid with farnesoid X receptor inhibitors resulted in a significant increase in #GLP-1 levels compared to lithocholic acid alone. - alteration of BAs composition, especially the reduced LCA, contributed to HTH induced #GLP-1 suppression through FXR activation.
• [#Deoxycholic acid] - #Ruminococcaceae families perform the subsequent 7α-dehydroxylation of CA and CDCA to respectively generate DCA and LCA, has been associated with #Intermittent Hypoxia and hypercapnia conditions
• - #Lachnoclostridium is described with higher microbial capacity for bile acid conversion through a 7α-dehydratase process38, explained the robust increase in LCA abundance. - #Lachnoclostridium produces trimethylamine (#TMA), which was turned into trimethylamine-N-oxide (#TMAO) in liver
• [#High ambient temperature, #High temperature and humidity] - High-temperature and humidity conditions > decrease in lithocholic acid levels

References Notes