Bile Acids ⇒ Secondary bile acids {90000320}

Shared Reference Notes

• [1.1] [#α-muricholic acid] 
  - Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with #Fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid. - Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue.
• [1.2] 
  - secondary bile acids regulate dendritic cells, macrophages, and natural killer cells
• [1.3] [#Bile Acids, #Primary bile acids] 
  - Both primary BAs and secondary BAs have been shown to interact agonistically or antagonistically with a family of nuclear (FXR) and G-protein-coupled receptors, collectively known as BA-activated receptors (BAR), influencing cellular signaling as well as immunological response
• [1.4] [#Diabetes Type 2] [#Akkermansia muciniphila] [#Short Chain Fatty Acid] [#Oral administration of Metformin] 
  - oral metformin has been shown to alter gut microbiome composition in obese adults with T2D, which was associated with secondary BA and FXR changes, resulting in improved insulin sensitivity - Metformin promotes colonization by SCFA-producing bacteria such as Akkermansia, Several studies of different ethnic populations with T2D and healthy individuals have demonstrated that metformin alters gut microbiome composition and is associated with changes in SCFA, BA, and C-peptide levels.
• [1.5] [#Ulcerative Colitis] [#Primary bile acids] 
  - colonic CD displayed a disease-severity-related association with #Bacteroides vulgatus. - Compared to colonic CD, ileal CD profiles displayed increased primary and secondary bile acid levels and concomitant shifts in taxa with noted sensitivities such as #Faecalibacterium prausnitzii or affinities for bile acid-rich environments, including #Gammaproteobacteria and #Blautia sp.
• [1.6] [#Bile Acids, #Primary bile acids] 
  - Intestinal bacteria will deconjugate primary BAs that fail reabsorption in the terminal ileum and thereby convert them to secondary BAs by microbial biotransformation, including dehydroxylation, epimerization, and oxidation of hydroxyl groups. - Free BAs, such as cholic acid, deoxycholic acid, and chenodeoxycholic acid, can stimulate apoptosis and reduce interleukin 6 (IL-6) production, while conjugated BAs such as glycolic acid, glycodeoxycholic acid, and glycochenodeoxycholic acid promote cell growth and induce IL-6 production.
• [#Hepatocellular cancer] - excessive production of the secondary BA deoxycholic acid triggers the expression of inflammatory and tumorigenic factors in hepatic stellate cells (HSCs), contributing to hepatocellular carcinoma development. Secondary BAs might also activate farnesoid X receptor (FXR) and elevate the risk of developing #Colorectal cancer and hepatocellular carcinoma.
• [#Inflamatory bowel disease] [#Bile Acids, #Primary bile acids] - Reduced BA deconjugation is associated with inflammatory bowel diseases (IBD) including #Ulcerative Colitis (UC) and #Crohn’s disease (CD), as well as #Irritable bowel syndrome (IBS).
• [1.7] [#Rheumatoid Arthritis] [#Bifidobacterium pseudocatenulatum] [#Probiotic Bifidobacterium pseudocatenulatum] 
  - In a collagen-induced arthritis (CIA) mouse model, B. pseudocatenulatum prevented joint damage by protecting the intestinal barrier and reshaped gut microbial composition, thereby elevating bile salt hydrolase (BSH) enzyme activity and increasing the levels of unconjugated secondary BAs to suppress aberrant T-helper 1/17-type immune responses
• [1.8] 
  - Roux-en-Y #Gastric bypass surgery (RYGB) > The changes in the fecal microbiome were linked to increased concentrations of #Branched-chain fatty acids and an overall decrease in secondary bile acid concentrations. - RYGB surgery also increased bile acid concentrations in plasma
• [1.9] 
  - #Covid-19 > Mortality was associated with increased representation of #Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and #Desaminotyrosine (DAT). - A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and #Desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation.
• [#Primary 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] [#Deoxycholic acid, #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] [#Deoxycholic acid] - 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.
• [1.11] [#Dementia with Lewy bodies (DLB)] 
  - #Ruminococcus torques and #Collinsella are also major secondary bile acids-producing bacteria, we quantified fecal bile acids and found that the production of #Ursodeoxycholic acid (UDCA) was high in DLB.
• [1.12] [#Inflamatory bowel disease] 
  - secondary bile acids escape hepatic recirculation, which reportedly, in turn, decreases #Cholesterol absorption and enhances its fecal excretion via modulation of farnesoid X receptor (FXR) signalling. - Microbial modulation of bile acid profiles has been linked to inflammatory bowel disease (IBD), with related FXR modifications as an underlying mechanism of gut barrier destabilisation
• [1.13] [#Short Chain Fatty Acid] 
  - SCFA such as #Butyrate, and secondary bile acids, might influence mitochondrial functions related to energy production, mitochondrial biogenesis, redox balance and inflammatory cascades, increased SIRT1 and FIAF activity, higher carbohydrate and fatty acid metabolism
• [#Reactive Oxygen Species, #Short Chain Fatty Acid] [#Sport] - the gut microbiota and its metabolites, such as short chain fatty acids and secondary bile acids, also contribute to host energy production, ROS modulation and inflammation in the gut by attenuating TNFα- mediated immune responses and inflammasomes such as NLRP3.
• [1.14] 
  - BSH activity fuels the production of MCBAs (microbial conjugated #Bile Acids)
• [1.15] [#Short Chain Fatty Acid] [#Exercise training] 
  - SCFAs, in response to aerobic exercise, can decrease the luminal pH (colon) by decreasing the conversion of #Primary bile acids to secondary bile acids and promoting colonic acidification. - The environment created as a result of these changes is more favorable for the growth of healthy commensal bacteria
• [1.16] 
  - BAs serve as signaling molecules with the ability to bind to receptors such as farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), constitutive androstane receptor (CAR), and more. - Each BA is able to bind with multiple receptor types with varying degrees of effec.t. - #Bile Acids can be conjugated with #Glycine, #Taurine, and to a lesser studied extent, other amino acids, which can affect the ability of BAs to act as substrates for specific receptors in the body.
• [1.17] [#Irritable bowel syndrome] 
  - significant difference in #Stearic acid levels between IBS patients and healthy individuals. - diet enriched with #Stearic acid led to reduced concentrations of fecal secondary bile acids (SBA). - These SBA can impact intestinal function, including factors like intestinal peristalsis and mucosal permeability, which may have a key role in the mechanism of IBS
• [1.18] [#Anxiety] [#Condition of chronic stress] 
  - increased secondary bile acids and reduced #Cholic acid in the serum of ex-germ free mice exposed to fecal material from stressed mice
• [1.19] 
  - #Parabacteroides distasonis alleviates #Obesity and metabolic dysfunctions via production of #Succinate and secondary bile acids. - Administration of #Parabacteroides distasonis leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal FXR signaling and decreased TCDCA levels in liver
• [#Diabetes Type 2] - stimulating the G-protein-coupled receptor 5 by gut-bacteria-derived secondary BAs influences #Glucose homeostasis through glucagon-like peptide-1 (#GLP-1) action.

References Notes