Fecal metaproteomics enables functional characterization of remission in patients with inflammatory bowel disease

Background: The gut microbiome is an important contributor to the development and the course of inflammatory bowel disease (IBD). While changes in the gut microbiome composition were observed in response to IBD therapy using biologics, studies elucidating human and microbial proteins and pathways in dependence on therapy success are sparse. Methods: Fecal samples of a cohort of IBD patients were collected before and after 14 weeks of treatment with three different biologics. Clinical disease activity scores were used to determine the clinical response and remission. Fecal metaproteomes of remitting patients (n=12) and of non-remitting patients (n=12) were compared before treatment and changes within both groups were assessed over sampling time to identify functional changes and potential human and microbial biomarkers. Results: The abundance of proteins associated with the intestinal barrier, neutrophilic granulocytes, and immunoglobulins significantly decreased in remitting patients. In contrast, an increase of those proteins was observed in non-remitting patients. There were significant changes in pathways of microbial metabolism in samples from patients with remission after therapy. This included, for example, an increased abundance of proteins from butyrate fermentation. Finally, new potential biomarkers for the prediction and monitoring of therapy success could be identified, e.g. human lysosome-associated membrane glycoprotein 1, a cytotoxicity marker, or microbial anthranilate synthase component 2, a part of the tryptophan metabolism. Conclusions: Distinct changes of proteins related to gut inflammation and gut microbiome metabolism showed whether IBD remission was achieved or not. This suggests that metaproteomics could be a useful tool for monitoring remission in IBD therapies.