A Golden Ratio for Gut Disorders
Could the permeability ratio be used to diagnose and monitor gut disorders less invasively than traditional colonoscopy?
Luke Turner | | Quick Read
Inflammatory bowel disease (IBD) is on the rise across the globe – especially in industrialized countries. By 2015, an estimated three million people in the US had received a diagnosis of either Crohn’s disease or ulcerative colitis, the two conditions collectively known as IBD (1). Characterized by chronic inflammation of the gastrointestinal tract, symptoms of the disease include stomach pain and swelling, bloody diarrhea, and weight loss. Typically, IBD is diagnosed and monitored through colonoscopy, which assesses structural damage to the intestine’s gut-blood barrier. But colonoscopy is invasive and requires anesthesia – and Marcin Ufnal of the Medical University of Warsaw might have found a better alternative.
Patients with IBD suffer from an impaired gut-blood barrier, which Ufnal and his team have harnessed to develop a novel test that compares the ratio of bacterial products in the patient’s blood and stool (2). “We initially wanted to use the concentration of gut bacterial products in the blood, but this didn’t work because there were significant inter-individual differences in bacterial composition, including geographic, dietary, and drug-related factors,” says Ufnal.
In contrast, the blood-to-stool ratio of bacterial products isn’t affected by differences in the composition and metabolic activity of bacteria. “The permeability ratio (Pr) assesses the extent to which bacterial products have passed through the gut-blood barrier,” Ufnal explains. “A healthy individual will have a low Pr, whereas the ratio for an IBD patient will be higher.” Specifically, the Pr analyzes short-chain fatty acids in just 1 mL of blood and stool, measuring their concentration via liquid chromatography coupled with triple-quadrupole mass spectrometry.
Ufnal believes that the technique could also be used to diagnose other disorders that affect the function of the intestinal wall, such as celiac disease. In addition, it offers promise for the detection of heart failure, high blood pressure, and liver ailments, because they may all result in a leaky gut that affects the concentration of bacterial products in the blood.
Future efforts will be directed toward assessing which bacterial metabolites are most useful in terms of calculating Pr. “We are doing a lot of basic research to look for bacterial products that aren’t metabolized by the liver, because that can affect their concentration in systemic blood,” says Ufnal. Given that gut disorders can develop before any structural changes can be seen with traditional colonoscopy, this method of diagnosing and monitoring IBD offers hope that symptoms can be controlled at the earliest stage.
- JM Dahlhamer et al., “Prevalence of Inflammatory bowel disease among adults aged ≥18 Years - United States, 2015”, MMWR Morb Mortal Wkly Rep, 65, 1166 (2016). PMID: 27787492.
- K Jaworska et al., “Inflammatory bowel disease is associated with increased gut-to-blood penetration of short-chain fatty acids: A new, non-invasive marker of a functional intestinal lesion”, Exp Physiol, [Epub ahead of print] (2019). PMID: 31243807.