Chyme Reinfusion Therapy (CRT) involves collecting proximal small bowel output (chyme) from an ostomy appliance and returning it to the distal small intestine. This process reestablishes intestinal continuity and rapidly reactivates physiological circuits suppressed by proximal diversion, such as a high-output ileostomy or enteroatmospheric fistula. The two most significant circuits affected by CRT are enterohepatic recycling and the ileal brake. Both influence nutrient, electrolyte, and drug absorption, as well as intestinal transit and stoma output1,2.

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Enterohepatic recycling

Under normal conditions, the liver secretes bile acids into the intestine to facilitate lipid digestion. These acids are actively reclaimed in the terminal ileum (the distal portion of the small intestine) via transporters and hormones like GLP-2, before returning to the liver via portal circulation.

• The Impact of Diversion: Proximal chyme loss leads to net bile depletion, impaired fat absorption, and compensatory hepatic synthesis (where the liver overproduces bile to compensate for the lack of recycling). This results in ongoing fluid and electrolyte losses3,4.

• The Role of CRT: By delivering bile-rich chyme back to the distal ileum, CRT restores the environment necessary for bile acid transporters and microbial transformations. This assists in recirculating bile acid, improves the absorption of fats and fat-soluble vitamins, and reduces the liver's compensatory overproduction, ultimately lowering stoma or fistula output2,4.

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The Ileal Brake

The "ileal brake" is a nutrient-sensing mechanism in the distal ileum. L-cells and other enteroendocrine cells detect fat and peptide fragments in chyme, triggering the release of hormones such as peptide YY (PYY) and glucagon-like peptide-1 (GLP-1).

• The Mechanism: These hormones slow gastric emptying and small-bowel transit, increasing the time available for nutrient absorption and thickening the output5,6.

• The Impact of Diversion: When chyme is diverted away from the terminal ileum, this negative feedback loop is disengaged, resulting in rapid transit and higher stoma output.

• The Role of CRT: CRT re-exposes the distal terminal ileum mucosa to nutrients, increasing L-cell signalling. This slows chyme transit and increases contact time throughout the small intestine, which reduces output volume by thickening the transiting chyme1,2.

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Effects on Medication Absorption

CRT can significantly alter the absorption of medications, particularly enterohepatic drugs (those that circulate between the intestine and liver). Slower small-bowel transit and restored distal exposure increase intestinal contact time, which can augment the absorption of drugs primarily taken up in the distal small bowel.

• Enterohepatic Recirculation: Drugs undergoing biliary secretion and intestinal reabsorption, such as Loperamide, may regain sustained plasma levels once bile acid recycling is reestablished4.

• Bioavailability Risks: Conversely, without CRT, agents relying on distal absorption or biliary reuptake may show reduced bioavailability, as the medication is lost to the ostomy appliance.

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Clinical Implications and Guidance

Any change in intestinal continuity—whether starting CRT or undergoing stoma reversal—should prompt a thorough medication review.

• Review Focus: Clinicians should focus on the drug absorption site, formulation (immediate vs. extended-release), and whether the drug undergoes enterohepatic recycling3,4. Monitoring should also be considered for agents with narrow therapeutic medications.

• Loperamide Use: Loperamide is a μ-opioid receptor agonist that reduces secretions and slows transit7. While its mechanism complements CRT, the combined effect of Loperamide and a reinstated ileal brake can cause constipation, bloating, and/or abdominal discomfort.

• Safety: High or inappropriate dosing poses safety concerns7,8. Loperamide should be used judiciously and titrated to effect while monitoring for obstructive symptoms or abdominal pain7.

Conclusion

• CRT reduces dependence on parenteral support in up to 80% of individuals by improving nutrient and bile salt absorption and by lowering stoma output1,2.

• Medication regimens should be reassessed when CRT begins or after stoma/fistula reversal, particularly weaning Loperamide, and consider therapeutic drug monitoring where available for narrow therapeutic medications or those with known involvement with enterohepatic recycling4.

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