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
• [1.16] 
  - Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in #Colorectal cancer (CRC) patients, - DCA is a negative regulator for CD8+ T cell effector function. - DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. - Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific #Bacteriophage.

References Notes