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The citrulline generation test: proposal for a new enterocyte function test.

J H C Peters1, N J Wierdsma, T Teerlink

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|March 12, 2008
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Summary

A new citrulline generation test (CGT) shows promise for assessing enterocyte function. This test, using an oral alanine-glutamine bolus, effectively measures plasma citrulline changes in healthy individuals and patients with conditions affecting enterocyte mass.

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Area of Science:

  • Gastroenterology
  • Biochemistry
  • Clinical Diagnostics

Background:

  • Enterocytes primarily produce citrulline from glutamine.
  • Fasting plasma citrulline is an unreliable biomarker for enterocyte dysfunction.
  • A novel citrulline generation test (CGT) is proposed to evaluate enterocyte function.

Purpose of the Study:

  • To evaluate the feasibility of the CGT in healthy subjects.
  • To assess CGT performance in patients with reduced enterocyte mass.
  • To establish CGT as a reliable diagnostic tool for enterocyte dysfunction.

Main Methods:

  • Administration of an oral 20g alanine-glutamine bolus to 19 healthy subjects and 25 patients (intestinal villous atrophy and short bowel syndrome).
  • Measurement of plasma citrulline and amino acid concentrations via reverse-phase high-performance liquid chromatography.
  • Analysis of time-dependent changes and incremental area under the curve (iAUC T90) for plasma citrulline.

Main Results:

  • Healthy subjects exhibited a significant time-dependent increase in plasma citrulline (44 +/- 13%, P < 0.0001).
  • CGT demonstrated reduced citrulline generation in patients with coeliac disease (CeD) and refractory CeD compared to healthy controls.
  • CGT differentiated between adapted and non-adapted short bowel syndrome (SBS) patients based on iAUC T90 (P = 0.04).

Conclusions:

  • An oral alanine-glutamine bolus reliably induces a time-dependent increase in plasma citrulline.
  • The magnitude of citrulline increase correlates with enterocyte status, reflecting villous atrophy or hyperplasia.
  • CGT is a feasible and effective method for assessing enterocyte function in various gastrointestinal conditions.