Increased Proteolytic Activity in Feces May Be Potential Biomarker of Ulcerative Colitis

ulcerative colitis
ulcerative colitis
A team of investigators studied a group of asymptomatic patients who were at increased risk of developing inflammatory bowel disease to assess proteolytic activity in advance of a diagnosis of ulcerative colitis.

Researchers from McMaster University in Canada identified increased proteolytic activity in feces that preceded a diagnosis of ulcerative colitis (UC), which may be a viable biomarker of disease. These findings were published in Gastroenterology.

A cohort of patients aged 6 to 35 years (n=61) who were first-degree relatives of patients with Crohn disease (CD) were recruited. Participants provided stool samples at enrollment and following a diagnosis of UC (n=9). A validation cohort (UC: n=7; CD: n=5; controls: n=23) donated stool samples to assess observations made among the first cohort.

Fecal samples were assessed for bacterial 16S ribosomal RNA and nonspecific proteolytic activity via direct infusion/liquid chromatography tandem mass spectrometry. Germ-free mice underwent microbiota colonization and were assessed for colonic health, and some colonized mice carried litters of pups.

The biodiversity of fecal samples differed significantly for Bray-Curtis (post-UC vs pre-UC: P =.02; vs controls: P =.02), unweighted UniFrac (post-UC vs pre-UC: P =.002; vs controls: P =.001), and Shannon (post-UC vs pre-UC: P =.03; vs controls: P =.03) diversity.

Post-UC samples had reduced Adlercreutzia equolifaciens (vs pre-UC: P =.01; vs controls: P =.041) and increased Actinobacillus (vs controls: P =.0001) and Flavonifractor plautii (vs controls: P =.01) abundance.

Unique pathways among pre-UC samples were L-arginine biosynthesis, biotin biosynthesis, polyamine biosynthesis, and tRNA charging. A total of 15 pathways were absent from controls but were found in pre- and post-UC samples, many of which involved amino acid and protein metabolism. Pre- and post-UC samples were depleted of glycerol and glycerophospholipid pathways compared with controls.

Proteolytic activity was decreased in post-UC samples (vs controls: P =.005), as was elastase activity (vs controls: P =.0006). This reduced proteolytic activity was confirmed among mice colonized with post-UC samples (vs pre-UC: P =.01; vs controls: P <.0001), as was the reduced elastase activity (vs controls: P =.006).

Similar reductions in proteolytic and elastase activity were observed among pups born to colonized mothers. The pups born to mice colonized with post-UC samples had reduced Shannon diversity (vs controls: P =.006), Bacteroidetes (vs pre-UC: P =.008), actinobacteria (vs pre-UC: P <.0001; vs controls: P =.0004), and Adlercreutzia (vs controls: P =.0002) abundance.

This study was limited by the low number of individuals who developed UC (n=13) and by the low number of individuals who provided a second fecal sample (n=9).

These data indicated that pathways were significantly different between healthy controls and individuals who had been or were going to be diagnosed with UC and may represent noninvasive biomarkers for disease risk and potential therapeutic targets.


Galipeau HJ, Caminero A, Turpin W, et al. Novel fecal biomarkers that precede clinical diagnosis of ulcerative colitis. Gastroenterology. 2020;S0016-5085(20)35533-5. doi:10.1053/j.gastro.2020.12.004