Certain Sugars Act as Potential Probes for Intestinal and Colonic Permeability

Investigators developed a potential diagnostic test based on oral monosaccharides and disaccharides to assess gut permeability using urinary excretion. This according to results from a study published in Gastroenterology.

The 60 healthy participants and 18 patients with diarrhea-predominant irritable bowel syndrome (IBS-D) were all subject to 3 randomized studies with a cross-over design. Fiber intake 24 hours before and after each study was standardized at 16.25g twice and at 32.5g once and the sugars ¹²C-mannitol, ¹³C-mannitol, rhamnose, sucralose, and lactulose were ingested.

Patients with IBS-D underwent the same procedure with the exception that only 2 sugars were administered orally, 100 mg of ¹³C-mannitol and 1000 mg of lactulose. Intestinal permeability was then evaluated based on urine excretion of probe molecules at 0-2 hours to reflect small bowel permeability and at 8-24 hours to reflect colonic permeability. Urine was also collected at 2-8 hours, though prior studies cannot attribute this sample to either small bowel or colon permeability with absolute certainty.

All 60 healthy participants had observable baseline levels of mannitol, with urine concentrations >10 μg/mL in 66% of participants. Other sugars were detected at baseline levels of >3-fold above lower limits of quantitation in varying numbers of participants across the 3 studies: 4-8 participants for sucralose, 1-3 for rhamnose, 1 for lactulose, and none for ¹³C-mannitol.

The median percent of excreted sugar molecules were 30%, 12.5%, 0.3% and 2.3% for ¹³C-mannitol, rhamnose, lactulose, and sucralose, respectively. The excretion profiles of ¹³C-mannitol and rhamnose were similar and both were absorbed primarily in the small intestine, with <2% median excretion reflecting colonic permeability. The intra-individual excretions were largely consistent, with some minor differences between the high and low fiber conditions. No significant effects of sex, age, or BMI on permeability measurements were detected.

In the IBS-D patient group, there were no significant group differences in excretion of ¹³C-mannitol and lactulose in the 3 urine collections. However, there were significant amounts of ¹²C-mannitol in all 3 collections, indicating inadvertent contamination. The median amounts of ¹³C-mannitol and lactulose excreted over 24 hours were comparable with those from healthy participants receiving 16.25g fiber diets.

Study limitations include the absence of data in patients with obesity and athe small sample size that lacked ethnic or racial diversity and pediatric age participants.

The study results show that ¹²C-mannitol is pervasive in many foods and precludes its use as a permeability probe. The low quantities of sucralose and lactulose absorbed calls into question their sensitivity as colonic permeability markers. “Our studies suggest that ¹³C-mannitol is the preferred probe for small intestinal permeability with highest excretion during 0-2 hours, followed by 2-8 hours, both of which reflect absorption through small bowel,” stated investigators. They added, “With further validation studies, it is conceivable that this test platform could be developed as a clinical diagnostic test based on ¹³C mannitol (0-2h collection reflecting small intestinal permeability) and the disaccharides lactulose or sucralose (2-8h collection reflecting permeability of both the small intestine and the colon) to measure permeability in vivo.”

Disclosure: Two authors have submitted a patent application regarding methods for assessing intestinal permeability. Please see the original reference for a full list of disclosures.

Reference

Khoshbin K, Khanna L, Maselli D, et al. Development and validation of test for “leaky gut” small intestinal and colonic permeability using sugars in healthy adults. Gastroenterol. Published online April 15, 2021. doi: 10.1053/j.gastro.2021.04.020