Gut Serpinome: Emerging Evidence in IBD

Abstract

Inflammatory bowel diseases (IBD) are incurable disorders whose prevalence and global socioeconomic impact are increasing. While the role of host genetics and immunity is well documented, that of gut microbiota dysbiosis is increasingly being studied. However, the molecular basis of the dialogue between the gut microbiota and the host remains poorly understood. Increased activity of serine proteases is demonstrated in IBD patients and may contribute to the onset and the maintenance of the disease. The intestinal proteolytic balance is the result of an equilibrium between the proteases and their corresponding inhibitors. Interestingly, the serine protease inhibitors (serpins) encoded by the host are well reported; in contrast, those from the gut microbiota remain poorly studied. In this review, we provide a concise analysis of the roles of serine protease in IBD physiopathology and we focus on the serpins from the gut microbiota (gut serpinome) and their relevance as a promising therapeutic approach.

Keywords: gut microbiota; gut serpinome; holobiont; inflammatory bowel diseases; proteases.

Figure 1

Schematic illustration of gut serpinome involvement in intestinal homeostasis and IBD. During homeostasis, the gut microbiota elicits an immune tolerance phenotype in the host. The activity of luminal serine and cysteine proteases is tightly regulated by their specific serpins of both gut microbial and host origin. A key feature of IBD is the alteration of the composition of the gut microbiota, dysbiosis, characterized by the decrease in microbial diversity with a loss of beneficial symbionts and the expansion of pathobionts. The dysregulation of the proteolytic balance with an increased protease activity over serpins alters the intestinal barrier and exacerbates inflammation. SCFA: short-chain fatty acid.