title: Age and Gender Affect the Composition of Fungal Population of the Human Gastrointestinal Tract.
abstract: The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here, we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal (GI) tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C), to acidic and oxidative stress, and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals' life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics-based approaches to fungal gut populations.
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund MachSan Michele all' Adige, Italy; Centre for Integrative Biology, University of TrentoTrento, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Strati
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Meyer Children's Hospital, University of Florence Florence, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Di Paola
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach San Michele all' Adige, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Stefanini
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach San Michele all' Adige, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Albanese
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach San Michele all' Adige, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rizzetto
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Meyer Children's Hospital, University of Florence Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lionetti
authors.affiliation: Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence Florence, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Calabrò
authors.affiliation: Centre for Integrative Biology, University of Trento Trento, Italy.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jousson
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach San Michele all' Adige, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Donati
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund MachSan Michele all' Adige, Italy; Department of Biology, University of Florence, Sesto FiorentinoFlorence, Italy.
authors.forename: Duccio
authors.initials: D
authors.lastname: Cavalieri
authors.affiliation: Institute of Biometeorology, National Research Council Florence, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: De Filippo
keywords: antifungal resistance; commensal fungi; fungal metagenomics; fungi-host interactions; human gut mycobiota