I recently read a blog post by Christy Clutter that discusses the role of fungi in Inflammatory bowel disease (IBD). IBD is characterized by immune hyperactivation that damages the intestine of about 3 million Americans, and includes Crohn’s disease and ulcerative colitis. Although 240 genetic variations associated with increased likelihood of IBD development have been identified, epidemiological studies show that strong environmental factors such as diet, antibiotic exposure, and smoking can affect individual susceptibility. Inappropriate immune responses to the microbes existing in the intestine could result in the development of IBD; therefore, it is important to understand how these environmental factors drive disease susceptibility in the gut microbiome.
Most microbiome research is focused on bacterial populations because they make up trillions of organisms, but bacteria are not the only microbes that inhabit the gut. Less than 1% of microbiota studies have included fungi which leaves current knowledge of microbiomes under characterized. Although most gut microbes are bacteria, fungi have been implicated in causal roles for gut microbial ecology and host immune functionality in mice (Bernardes, et al. 2020). Current sequencing tools for fungi and bacteria are similar, but there is a lack of diversity in the species identified due to sampling, and data analyses methods are biased to a small set of over-represented species. The author states that fungal reference databases used to identify sequences are "fledgling", and that bioinformatic ability to trust these taxonomic identifications is imperfect. I would argue that current databases of fungi sequencing data are suitable for trustworthy phylogenetic and taxonomic identifications. The National Center for Biotechnology Institute has a plethora of fungi sequence data that is updated daily, most notably to mycologists is the Fungal RefSeq database that includes more than 200 species (Robbertse & Tatusova 2011). Most fungi identified in the clinical laboratories are yeast, and all 1,200 known species of yeast have now been sequenced by the Y1000+ Project (Shen, et al. 2018). The Y1000+ Project has sequenced the highest number of fungal species thus far, and the final version of the publicly available database will include all yeast fungal species (https://y1000plus.wei.wisc.edu/).
Scientists studying IBD have taken interest in fungi because like bacteria, they are ubiquitous in the body, and are sensitive to environmental factors such as diet. Patients with Crohn's disease have elevated circulating antifungal antibodies, and some species such as Candida albicans actively worsen inflammatory colitis in mice (Jawhara, et al. 2008). Fungi influence bacterial dynamics in the gut by acting in cooperation with host infection and biofilm production. For example, Candida tropicals can work with bacteria such as Escherichia coli and Serratia marcescens to generate a "monstrous biofilm", as well as induce the expression of fungal markers for pathogenicity (Hoarau, et al. 2016). Recent studies have shown that there is dysbiosis not only with bacterial species but also fungal species in patients with IBD. There exists inherent competition between fungi and bacteria within the gut, which means that antibiotics used to treat intestinal disease can disrupt more than just bacterial communities. Antibiotics selectively eliminate specific bacteria while leaving fungal species undisturbed, thus they can change the dysbiosis in the gut microbiome resulting in higher prominence of fungal species. Even though there is much research on the gut microbiome, little is still known about the diversity of its key microbial players. Databases such as Fungal RefSeq and Y1000+ could be a great resource in the development of specialized methods for identifying which fungal species contribute to the gut microbiome of patients with IBDs.
References
Bernardes E., Pettersen V.K., Gutierrez M.W., Laforest-Lapointe I., Jendzjowsky N.G., Cavin J.B., Vicentini F.A., Keenan C.M., Ramay H.R., Samara J., MacNaughton W.K., Wilson R.A., Kelly M.M., McCoy K.D., Sharkey K.A., Arrieta M.C. (2020). Intestinal fungi are causally implicated in microbiome assembly and immune development in mice. Nat Commun. 11(1):2577. doi: 10.1038/s41467-020-16431-1.
Hoarau, G., Mukherjee, P.K., Gower-Rousseau, C., Hager, C., Chandra, J., Retuerto, M.A., Neut, C., Vermeire, S., Clemente, J., Colombel, J.F., Fujioka, H., Poulain, D., Sendid, B., Ghannoum, M.A (2016). Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn's Disease. mBio, 7(5):e01250-16. https://doi.org/10.1128/mBio.01250-16
Jawhara, S., Thuru, X., Standaert-Vitse, A., Jouault, T., Mordon, S., Sendid, B., Desreumaux, P., Poulain, D. (2008). Colonization of Mice by Candida albicans Is Promoted by Chemically Induced Colitis and Augments Inflammatory Responses through Galectin-3, The Journal of Infectious Diseases, 197(7), 972–980. https://doi.org/10.1086/528990
Robbertse, B., & Tatusova, T. (2011). Fungal genome resources at NCBI. Mycology, 2(3), 142–160. https://doi.org/10.1080/21501203.2011.584576
Shen, X.X., Opulente, D.A., Kominek, J., Zhou, X., Steenwyk, J.L., Buh, K.V., Haase, M.A.B., Wisecaver, J.H., Wang, M., Doering, D.T., Boudouris, J.T., Schneider, R.M., Langdon, Q.K., Ohkuma, M., Endoh, R., Takashima, M., Manabe, R.I., Cadez, N., Libkind, D., Rosa, C.A., DeVirgilio, J., Hulfachor, A.B., Groenewald, M., Kurtzman, C.P., Hittinger, C.T., Rokas, A. (2018). Tempo and mode of genome evolution in the budding yeast subphylum. Cell 175: 1533-45. https://doi.org/10.1016/j.cell.2018.10.023
