Distal Fecal Wash: Intestinal Liquid Biopsy?

Over the past decade, fecal biomarkers, and here in particular calprotectin, have entered clinical practice and guidelines for monitoring disease activity in inflammatory bowel diseases (IBDs).¹ However, the concentration of calprotectin in the fecal sample only reflects inflammatory activity, which can be located anywhere from the rectum to the ileum. Thus, calprotectin does not allow for determining the site of inflammation. In previous work, Ungar et al² introduced the concept of fecal washes and showed that fecal transcriptomes correlate with histologic and endoscopic markers in patients with distal colitis. Remarkably, the fecal wash transcriptomics showed a better correlation with local histology when compared with biopsy transcriptomics.² The term fecal wash suggests that some kind of washing occurs before the sample is taken. However, only intestinal fluid at the indicated site was suctioned and processed. Thus, it is not surprising that Ungar et al² could identify immune cell populations in the fecal wash of patients with distal colitis where the intestinal barrier was disrupted. The shedding or release of immune cell populations into the intestinal lumen has been described previously in mice. In these publications, distinct lymphocyte subpopulations were identified and shown to be viable for several hours.^3,4 Based on these earlier findings, Dan et al⁵ aimed to test the hypothesis of whether fecal wash transcriptomics can serve not only to determine the severity, but furthermore even the site of inflammation in patients with IBD. Supporting this hypothesis was prior strong evidence indicating that the expression profile of ileitis is clearly distinct from that of colitis.⁶

In the study presented in this issue of Cellular and Molecular Gastroenterology and Hepatology, 59 IBD patients as well as 50 controls were included and biopsy specimens as well as washes were obtained from the ileum and the proximal and distal colon. Transcriptomics of fecal washes and biopsy specimens were associated with the clinical, endoscopic, and histologic parameter. In line with the earlier work, the local fecal wash transcriptomes were associated with endoscopic and histologic inflammation at the respective site. More intriguingly, transcriptomics of distal fecal washes allowed for classifying histologic inflammation in the ileum as well as proximal colon even in the absence of distal inflammation. Based on the recently defined gene modules by the Powrie group, the transcriptomic patterns could be clustered in the suggested modules and consisted of epithelial, immune, and stromal cells.⁷ From these data Ungar et al² concluded that distal fecal wash transcriptomics can serve as a novel tool for identifying and scoring the inflammatory location and severity throughout the ileal–colonic axis. Although this approach certainly requires a prospective validation, it is tempting to speculate whether this methodology could partially replace endoscopies and through this establish the next level of disease monitoring. In oncology, the molecular view of the individual disease is key for clinical decision making, this includes distinct expression patterns in the tissue, but also in the blood, better known as liquid biopsy. However, very similar to IBD, the biopsy and tissue analyses only provide a local snapshot of the tumor and potentially misses critical information. By taking blood samples, and hence a liquid biopsy, one can get this information throughout the disease course and guide the therapy accordingly.⁸

The fecal wash technique takes advantage of the luminal nature of IBD and thus the possibility for molecular evaluation. Very similar to the liquid biopsy in oncology, this approach could serve to monitor disease over time and therefore expand our view from more than simple disease activity to instead include disease location as well as a molecular perspective. In addition, as suggested by Ungar et al,² these analyses need to be explored in even more proximal disease locations.