The host-adapted commensal fungus provides cross-kingdom protection

Fungi are ubiquitous in the environment and, like bacteria, are an integral part of the gut microbiome. However, unlike bacteria, fungal species that can stably colonize the murine gut and model commensal behavior remain elusive. Here, we show that Kazachstania pintolopesii, a dominant fungus found in pet store mice from geographically distinct regions, stably colonized laboratory mice. K. pintolopesii outcompeted other fungi and maintained stable colonization independent of gut bacteria. We find that K. pintolopesii does not induce a typical antifungal response in murine hosts locally in the gut or upon systemic challenge. Accordingly, K. pintolopesii colonization did not afford protection against systemic fungal infection by Candida albicans. Instead, K.pintolopessii colonization increased type 2 immune responses in the intestine and protected mice against helminth infection. Overall design: To investigate the role of commensal fungus in the small intestine, murine-derived fungus was treated to mice via oral route. After two weeks, the small intestine of mice were harvested and processed for bulk RNA -seq.