Enterohepatic Circulation and Compound Metabolism

The Bile Pathway: From Liver to Intestine

The liver continually produces bile, a fluid containing bile acids, cholesterol, phospholipids, and Phase II-conjugated compounds awaiting elimination. Bile is concentrated in the gallbladder and released into the small intestine during digestion. This bile carries Phase I and Phase II-processed compounds from the liver into the intestinal lumen.

In the small intestine, the majority of bile acids and their conjugated compounds are reabsorbed back into the bloodstream through specialised transport mechanisms in the terminal ileum. This recycling is called enterohepatic circulation. Approximately 95% of bile acids are recycled this way, returning to the liver via the portal vein for re-excretion into bile. This cycle repeats 4–12 times daily in a healthy individual.

Efficiency of Recycling

Enterohepatic circulation is not a deficiency or problem; it is a normal, essential process. Recycling bile acids is energetically efficient and allows the body to regulate cholesterol homeostasis and maintain adequate bile acid pools. This process occurs continuously, regardless of dietary protocol.

Fecal Elimination Pathway

Bile acids and conjugated compounds that are not reabsorbed in the ileum continue into the colon, where they are eliminated via faeces. Additionally, faecal elimination includes:

• Unabsorbed dietary components
• Desquamated intestinal epithelial cells (the gut lining sheds continuously)
• Bacterial metabolites
• Compounds deconjugated by colonic bacteria (which possess Phase II enzymatic activity)

The colon naturally evacuates faecal matter through established motility patterns (peristalsis). No special dietary intervention, colon cleanse, or supplement enhances this natural process beyond baseline function in healthy individuals.

Bacterial Deconjugation and Beta-Glucuronidase Activity

Colonic bacteria express an enzyme called beta-glucuronidase, which can reverse Phase II glucuronidation—removing the glucuronic acid group and regenerating the original compound or a deconjugated metabolite. Some of these deconjugated compounds are reabsorbed via the colon and return to the liver for re-processing (another form of enterohepatic circulation). Others are excreted in faeces.

The activity of bacterial beta-glucuronidase varies between individuals based on microbiome composition and is influenced by factors such as antibiotic use, dietary fibre intake, and probiotics. However, this bacterial enzymatic activity occurs as part of normal microbiome function, not because of detox protocols. In fact, many detox-oriented dietary changes (fasting, severe restriction, elimination diets) can disrupt normal microbiome composition, potentially impairing rather than enhancing detoxification efficiency.

Compound Metabolism: A Continuous Process

The journey of a compound from entry (ingestion, inhalation, absorption) through Phase I, Phase II, enterohepatic circulation, and elimination is continuous and automatic. The body does not "activate" or "rest" these pathways. They operate 24/7 at baseline capacity determined by genetics, current nutritional status, and physiological state.

Why "Detox" Protocols Do Not Enhance Elimination

Detox protocols claim to "enhance" elimination, "activate the liver," or "reset metabolism." However:

• Phase I and II enzyme capacity is fixed (genetically determined) in the short term
• Enterohepatic circulation and faecal elimination occur whether or not a detox protocol is followed
• Extreme restriction may impair these processes by depleting cofactors required for optimal enzyme function
• Dehydration during fasting or restrictive protocols impairs kidney function, potentially reducing urinary excretion efficiency

If anything, well-balanced, nutrient-dense eating patterns support optimal detoxification more effectively than restriction.

Individual Variation in Enterohepatic Circulation

The efficiency of enterohepatic circulation varies based on:

• Ileal transporter expression—genetic variation in bile acid transporter genes
• Fibre intake—adequate fibre supports regular bowel motility
• Microbiome composition—bacterial populations influence deconjugation and reabsorption
• Digestive health—inflammatory bowel conditions, motility disorders, or enzyme insufficiency can alter this process
• Medications—some drugs bind bile acids, reducing reabsorption

Supporting optimal enterohepatic circulation involves adequate fibre, regular physical activity, stress management, and balanced nutrition—not detox protocols.