Gut Microbiota beyond Bacteria-Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD

Abstract

The human microbiota is a diverse microbial ecosystem associated with many beneficial physiological functions as well as numerous disease etiologies. Dominated by bacteria, the microbiota also includes commensal populations of fungi, viruses, archaea, and protists. Unlike bacterial microbiota, which was extensively studied in the past two decades, these non-bacterial microorganisms, their functional roles, and their interaction with one another or with host immune system have not been as widely explored. This review covers the recent findings on the non-bacterial communities of the human gastrointestinal microbiota and their involvement in health and disease, with particular focus on the pathophysiology of inflammatory bowel disease.

Keywords: archaeome; eukaryotic parasites; gut microbiota; inflammatory bowel disease (IBD); mycobiome; virome.

Figure 1

A schematic representation of intestinal mucosa in (A) healthy and (B) inflammatory bowel disease (IBD)-affected individual. A thick mucus layer covers the epithelium of the healthy intestine. Microbiota is dispersed throughout the outer mucus layer, while the inner layer is thick and resistant to penetration due to antimicrobial peptides secreted by epithelial cells, and immunoglobulin A (IgA). Commensal microbiota suppresses the proliferation of pathobionts and pathogens, tuning the host responses towards immunological tolerance and intestinal homeostasis. Various factors can disrupt the composition of intestinal microbiota, resulting in dysbiosis and excessive reproduction of pathogenic microorganisms. These species produce and secrete toxins, thinning the protective mucus layer, damaging the intestinal mucosa, and increasing intestinal permeability. The microbes can gain access to epithelial cells and mucosal tissue inducing the imbalance of the T_REG/T_H17 axis and thus a strong inflammatory response by the host immune system leading to or aggravating IBD.