Cells in Fecal Wash a More Powerful Biomarker Than Biopsy for IBD Inflammation

By Marilynn Larkin

February 11, 2022

NEW YORK (Reuters Health) - In patients with inflammatory bowel disease (IBD), a fecal wash sample yields more information about histological inflammation than a biopsy sample, and may help inform diagnosis, disease monitoring and treatment selection, researchers say.

"Our lab reasoned that the cells that are shed from the gastrointestinal tract could carry information that would report on pathological processes in the gut," Dr. Shalev Itzkovitz of the Weizmann Institute of Science in Rehovot, Israel, told Reuters Health by email. "We therefore sequenced the mRNA content (the host transcriptome) of fecal washes in inflamed IBD patients and in controls."

"To our surprise, we found that the transcriptomes of the fecal washes were much more indicative of active inflammation compared to the transcriptomes of biopsies," he said. "We believe this is due to the fact that our feces contain cells that are shed throughout the gastrointestinal tract. As a result, fecal wash measurements are less sensitive to the precise location from which biopsies are obtained."

"Moreover," he added, "we found that immune cells are over-represented in the fecal content compared to the tissue. Our feces therefore act as an extract of the cells that are most relevant to the inflammatory process."

As reported in Gut, Dr. Itzkovitz and colleagues analyzed biopsies and fecal washes from 20 IBD patients (median age 49; 55%, women) and 19 controls (median age, 67; 58%, women). They did RNA sequencing of all samples, and associated them with endoscopic and histological inflammation status.

Information from the host fecal transcriptome was distinct from that of biopsy RNAseq and fecal proteomics. Transcriptomics of fecal washes - but not of biopsies- from patients with histological inflammation were significantly correlated to each other; they also had significantly higher statistical power in identifying histological inflammation compared with the transcriptome of intestinal biopsies (150 genes with area under the curve >0.9 in fecal samples vs. 10 genes in biopsy RNAseq).

The results were replicated in a validation cohort of 10 IBD patients and 12 controls. Fecal samples were enriched with inflammatory monocytes, regulatory T cells, natural killer cells and innate lymphoid cells.

The authors state, "Expression levels of mRNA in fecal washes discriminate between histologically inflamed and non-inflamed patients significantly better than mRNA expression of colonic biopsies."

Dr. Itzkovitz added "We believe fecal wash host transcriptomics has a potential not only to identify flare episodes in IBD, but also to tailor specific biologic treatments to patients, based on the transcriptomes of the immune cells in their gut, as reflected by the fecal wash measurements."

"Since there is a high rate of non-responders to these drugs, a non-invasive biomarker with predictive power for drug selection is critical," he said. "In follow-up studies, we are currently working to establish the statistical power of fecal washes for predicting response to therapy, and are optimizing our method to yield comparative transcriptomic signal on stool samples."

Dr. Jordan Axelrad, a gastroenterologist at NYU Langone's Inflammatory Bowel Disease Center in New York City, commented on the study in an email to Reuters Health. "The results seem quite feasible, especially since these data were further confirmed in a validation cohort."

However, he said, "this study comprised a small sample size with lack of subgroup analysis by IBD subtype, phenotype, or therapeutic response. In addition, transcriptomics has limited clinical utility at present. Future studies should include a large, more diverse IBD population, and focus on the relationship between the transcriptome of fecal washes with IBD therapy response and outcomes."

SOURCE: https://bit.ly/3sxhh71 Gut, online January 19, 2022.

processing....