Unveiling the overlooked fungi: the vital of gut fungi in inflammatory bowel disease and colorectal cancer

Abstract

The fungi of the human microbiota play important roles in the nutritional metabolism and immunological balance of the host. Recently, research has increasingly emphasised the role of fungi in modulating inflammation in intestinal diseases and maintaining health in this environment. It is therefore necessary to understand more clearly the interactions and mechanisms of the microbiota/pathogen/host relationship and the resulting inflammatory processes, as well as to offer new insights into the prevention, diagnosis and treatment of inflammatory bowel disease (IBD), colorectal cancer (CRC) and other intestinal pathologies. In this review, we comprehensively elucidate the fungal-associated pathogenic mechanisms of intestinal inflammation in IBD and related CRC, with an emphasis on three main aspects: the direct effects of fungi and their metabolites on the host, the indirect effects mediated by interactions with other intestinal microorganisms and the immune regulation of the host. Understanding these mechanisms will enable the development of innovative approaches based on the use of fungi from the resident human microbiota such as dietary interventions, fungal probiotics and faecal microbiota transplantation in the prevention, diagnosis and treatment of intestinal diseases.

Keywords: Colorectal cancer; Fungus; Inflammatory bowel disease; Intestinal inflammation.

Fig.1

Direct action of fungal bodies or metabolites on the gut barrier. Fungi can directly affect the intestinal epithelial barrier through their mycelium or metabolites, exhibiting both protective and destructive effects. Their actions can involve interacting with intestinal epithelial cell receptors, which can activate or inhibit corresponding signaling pathways. This interaction may directly cause cell damage or alter the expression of tight junction proteins between cells, thereby affecting the risk of intestinal inflammation

Fig.2

Fungal interaction with other gut microbiota. Fungi can also affect the structure and diversity of the gut microbiota, thereby indirectly influencing the tight junctions of intestinal epithelial cells and the integrity of the intestinal barrier. These effects are similarly dual-faceted, ultimately resulting in either a reduced risk of intestinal inflammation or various scenarios in which gut microbial infections result in inflammation

Fig.3

Immunoregulatory effects of fungi. Fungi and their metabolites can also affect local or systemic immune systems by influencing the expression of immune pathways, the metabolism of immune cells, and the production of cytokines, thereby impacting the occurrence of inflammation and the risk of related intestinal diseases