Deoxycholic acid {90000228}

Shared Reference Notes

• [1.1] [#Bile Acids] 
  - Microbiota > higher levels of the microbiota-derived secondary bile acid deoxycholic acid and Gram-positive gut microbial component, #Lipoteichoic acid > These compounds induced senescence of hepatic stellate cells (HSCs) and the secretion of pro-inflammatory SASP > creating a pro-tumorigenic microenvironment.
• [1.2] 
  - Primary #Bile Acids by the intestinal flora > secondary bile acid Deoxycholic acid > cause inflammatory reactions
• [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.
• [#Colon adenomas, #Colorectal cancer] [#Secondary bile acids, #Ursodeoxycholic acid] - UDCA has microbiome-changing and DCA‐lowering prpperties. - treatment with UDCA, decreased recurrence of adenomas with high-grade dysplasia. - DCA also stimulates the uptake of polyamines in CRC cells, which also have tumorigenic effects.
• [#Colorectal cancer] [#Secondary bile acids] - Elevated levels of fecal SBAs, especially DCA, are associated with an increased risk for CRC. - FXR, receptor for #Bile Acids, is downregulated in CRC and low levels of FXR expression correlate with worse clinic outcomes.
• [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.
• [#Stroke] - DCA could improve acute cerebral infarction (ACI) induced nerve damage by inverting the Nrf2 signaling pathway.
• [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] 
  - #Tyramine, deoxycholic acid, and #4-aminobenzoic acid have been reported to stimulate #Serotonin synthesis
• [#Blood Brain Barrier Integrity] - deoxycholic acid and #Ursodeoxycholic acid, may also modulate BBB integrity.
• [1.8] 
  - #High ambient temperature of 36 °C increases host resistance to viral pathogens including #Influenza virus and severe acute respiratory syndrome #Coronavirus 2 (SARS-CoV-2). - High heat-exposed mice increase basal body temperature over 38 °C to enable more #Bile Acids production in a gut microbiota-dependent manner. - The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to #Influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. - the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. certain #Bile Acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group.
• [1.9] 
  - #Walnut consumption also decreased pro-inflammatory #Bile Acids deoxycholic acid and #Lithocholic acid and serum LDL #Cholesterol
• [#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
• [1.11] [#Cancer] [#Bile Acids, #Lithocholic acid] 
  - Secondary BA, DCA, and LCA can cause DNA damage
• [#Colitis] - In a mouse model, DCA supplementation increased oxidative damage in colonic epithelium
• [#Eggerthella lenta] [#Bile Acids, #Lithocholic acid] - E. lenta gavage also altered BA metabolism as observed by increased primary and secondary BA including DCA and lithocholate (LCA)
• [1.12] [#Diabetes Type 1] [#Bile Acids] 
  - stool concentrations of secondary BAs, particularly UDCA, DCA, HDCA, and their #Glycine and/or #Taurine conjugates, were downregulated in P2Ab versus P1Ab and/or CTR groups.
• [1.13] [#Crohn’s disease] [#Bile Acids, #Lithocholic 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
• [1.14] [#Alzheimer’s disease] 
  - AD patients > DCA and its conjugated forms with #Glycine and #Taurine increased, and deoxycholic acid was associated with decreased cognitive abilities
• [1.15] [#Lithocholic 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

References Notes