Secondary bile acids represent a fascinating intersection of human physiology and microbial metabolism. While your liver produces primary bile acids to digest fats, gut bacteria transform these compounds into secondary bile acids with distinct—and sometimes surprising—effects on health [^wahlstrom2016].
The Bile Acid Story
Primary Bile Acids: Made by You
Your liver synthesizes two primary bile acids from cholesterol:
- Cholic acid (CA)
- Chenodeoxycholic acid (CDCA)
These are conjugated with glycine or taurine and stored in the gallbladder until needed for fat digestion.
Secondary Bile Acids: Made by Bacteria
When primary bile acids reach the colon, specific gut bacteria transform them through a process called 7α-dehydroxylation:
- Cholic acid → Deoxycholic acid (DCA)
- Chenodeoxycholic acid → Lithocholic acid (LCA)
A third secondary bile acid, ursodeoxycholic acid (UDCA), is produced through a different bacterial pathway and has notably different health effects [^ridlon2014].
The Enterohepatic Circulation
Bile acids follow a remarkable recycling pathway:
- Synthesis: Liver produces primary bile acids
- Storage: Gallbladder concentrates and stores them
- Release: Fat consumption triggers gallbladder contraction
- Digestion: Bile acids emulsify fats in the small intestine
- Reabsorption: ~95% reabsorbed in the ileum
- Bacterial modification: ~5% reach the colon where bacteria create secondary bile acids
- Recycling: Secondary bile acids are reabsorbed and returned to the liver
This cycle repeats 6-10 times daily, with the bile acid pool circulating continuously.
Signaling Functions
Beyond fat digestion, bile acids are powerful signaling molecules:
FXR (Farnesoid X Receptor)
- Regulates bile acid synthesis
- Influences glucose metabolism
- Affects lipid metabolism
- Modulates immune responses
TGR5 (G Protein-Coupled Bile Acid Receptor)
- Increases energy expenditure
- Stimulates GLP-1 release
- Anti-inflammatory effects
- Found in many tissues
Other Receptors
- Vitamin D receptor (VDR)
- Pregnane X receptor (PXR)
- Constitutive androstane receptor (CAR)
Health Implications
Secondary bile acids have complex, context-dependent effects:
Potential Benefits
- Metabolic regulation through FXR/TGR5 signaling
- Antimicrobial properties (shape microbiome composition)
- Energy homeostasis
- Glucose regulation
Potential Concerns
- Elevated DCA associated with colorectal cancer risk
- High levels may damage the gut lining
- LCA is potentially toxic at high concentrations
- Imbalanced bile acids linked to various diseases
Bacteria Involved in Bile Acid Metabolism
Bile Salt Hydrolases (Deconjugation)
Many bacteria can remove the conjugated amino acids:
- Lactobacillus species
- Bifidobacterium species
- Bacteroides species
- Clostridium species
- Enterococcus species
7α-Dehydroxylation (Secondary Bile Acid Production)
Only specific bacteria perform this key transformation:
- Clostridium scindens
- Clostridium hiranonis
- Clostridium hylemonae
- Certain Eubacterium species
The limited number of bacteria capable of 7α-dehydroxylation means secondary bile acid production can be dramatically affected by microbiome changes.
Clinical Significance
Dysbiosis and Bile Acids
Antibiotic use can eliminate 7α-dehydroxylating bacteria, dramatically reducing secondary bile acid production. This may contribute to:
- C. difficile susceptibility (secondary bile acids inhibit C. diff)
- Altered fat absorption
- Metabolic changes
Liver Disease
Bile acid metabolism is disrupted in liver diseases:
- Cirrhosis alters the bile acid pool
- Primary biliary cholangitis affects bile flow
- NAFLD/NASH linked to bile acid signaling changes
Colorectal Cancer
High secondary bile acid levels, particularly DCA, are associated with increased colorectal cancer risk—especially with high-fat, low-fiber diets.
Metabolic Syndrome
Bile acid signaling dysfunction may contribute to:
- Insulin resistance
- Obesity
- Type 2 diabetes
Testing Bile Acid Levels
Various tests can assess bile acid status:
- Serum bile acids: Total and fractionated levels
- Stool bile acids: Reflect bacterial transformation
- Specialized panels: Ratios and specific bile acid species
Interpretation
- High DCA may indicate excessive bacterial conversion
- Low secondary bile acids may suggest dysbiosis
- Patterns can indicate specific conditions (e.g., bile acid malabsorption)
Modulating Bile Acid Metabolism
Dietary Factors
- High-fat diets increase bile acid production
- High-fiber diets may reduce secondary bile acid exposure
- Certain foods contain bile acid binders
Medications
- UDCA is used therapeutically for liver conditions
- Bile acid sequestrants (cholestyramine) affect bile acid cycling
- FXR agonists are being developed for metabolic diseases
Microbiome Interventions
- Specific probiotics may influence bile acid metabolism
- Prebiotics support beneficial bacterial communities
- Fecal microbiota transplant can restore bile acid-transforming bacteria
