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Table 1 Intestinal permeability evaluation methods

From: Intestinal barrier functions in hematologic and oncologic diseases

Method

Basis

Strengths

Weaknesses

Lactulose: Mannitol test

Both lactulose and mannitol are non-metabolized sugar molecules, but only mannitol is significantly absorbed following oral administration because it is smaller. The ratio of lactulose to mannitol measured in the urine provides an index of the permeability of the intestinal barrier. The higher the L: M ratio, the leakier is the intestinal barrier

Easy and inexpensive to administer and can be readily performed in the clinic without special training. Non-invasive

Normal range in healthy individuals still require to be established. Longitudinal collection of urine may be challenging in some patients, e.g. infants

Low molecular weight polyethylene glycol (PEG 400)

PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes. It is not degraded by intestinal bacteria, and not metabolized after absorption. It is rapidly excreted in the urine. Measurements of the PEG of different molecular weight provide a characterization of the passive permeability of the mucosa

51-EDTA

Measurements of the urinary radioactive EDTA following oral administration of the readily absorbed probe

Non-invasive

Handling of radio-isotope

Confocal laser endomicroscopy (CLE)

Involves injection of a fluorescein contrast agent to the patient and examining the cells and intracellular substance of the gastrointestinal tract mucosa during real-time endoscopy

Real-time observation of intestinal permeability

Invasive. Not readily available. Need special training

Serum biomarkers

Measure the traverse of lipopolysaccharides across the intestinal barrier or shedding of enterocyte-derived proteins

Non-invasive. Easy to perform

Different marker denotes a different endpoint and significance. Variability of methods for measurements. Lipopolysaccharides are also elevated during sepsis