Interpersonal variability in gut microbial calprotectin metabolism

Background: The gold standard for staging (i.e. defining severity and distribution of inflammation) in patients with inflammatory bowel diseases (IBD) is endoscopy with biopsies. However, it is not feasible to obtain endoscopic and histologic data frequently. Therefore, there is a clinical need for reliable non-invasive testing to monitor IBD patients. Fecal calprotectin is a promising but imperfect biomarker for disease activity, as it can be deceptively low despite active inflammation. We hypothesized that the gut microbiome can metabolize calprotectin and thereby alter its fecal measurements. Methods: We recruited 22 individuals from an academic IBD clinic. We collected clinical data and fecal samples. Using ELISA, we quantified fecal calprotectin. Using a novel ex vivo functional assay, we characterized gut microbial calprotectin degradation in each patient microbiome. We performed this assay in two different bacterial growth media containing high or low levels of free amino acids. Results: We found that the gut microbiome can modulate calprotectin levels in a manner dependent upon free amino acid levels in growth media, typically reducing calprotectin to a significantly greater extent in the low amino acid environments. Microbiome-mediated calprotectin degradation varied between individuals and was significantly greater in ulcerative colitis than Crohn's disease. Subdoligranulum abundance was correlated with observed reduction in measured calprotectin. We demonstrate in vitro that Subdoligranulum variabile degrades calprotectin to a significantly greater degree than a control strain. Conclusions: The gut microbiome may alter measured fecal calprotectin levels in IBD patients.