The microbiota is known to influence several facets of mammalian development, digestion and disease. Most studies of the microbiota have focused on the bacterial component, but the importance of commensal fungi in health and disease is becoming increasingly clear. Although fungi account for a smaller proportion of the microbiota than bacteria by number, they are much larger and therefore account for a substantial proportion of the biomass. Moreover, as fungi are eukaryotes, their metabolic pathways are complex and unique. In this Review, we discuss the evidence for involvement of specific members of the mycobiota in intestinal diseases, including inflammatory bowel disease, colorectal cancer and pancreatic cancer. We also highlight the importance of fungal interactions with intestinal bacteria and with the immune system. Although most studies of commensal fungi have focused on their role in disease, we also consider the beneficial effects of fungal colonies in the gut. The evidence highlights potential opportunities to target fungi and their interactions for therapeutic purposes.
Fungi are normal members of the human intestinal microbiome that activate immune pathways that are distinct from those activated by bacteria.
Intestinal fungal populations expand and their normal colonization niches change during inflammation or cancer.
Fungal colonization of inflamed intestinal epithelial tissue in inflammatory bowel disease or of tumours activate immune responses that exacerbate pathogenic inflammation, inhibit damage repair pathways and/or inhibit antitumour immune responses.
During homeostasis, some fungi — including those in the Candida genus — activate T helper 17 cells and antibody-producing plasma cells that protect against intestinal and systemic infections.
Intestinal bacteria limit fungal colonization through production of antifungal toxins and metabolites and by activating immune pathways; consequently, broad spectrum antibiotics are associated with increased fungal colonization, especially by Candida species.
Fungi have complex life cycles that often include morphological transitions that influence their ability to adhere to host tissue, secretion of host-damaging toxins, proficiency for gut colonization, and secretion of metabolites.
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The authors declare no competing interests.
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Ost, K.S., Round, J.L. Commensal fungi in intestinal health and disease. Nat Rev Gastroenterol Hepatol 20, 723–734 (2023). https://doi.org/10.1038/s41575-023-00816-w