The role of gut mycobiome in health and diseases

Abstract

The gut microbiome comprised of microbes from multiple kingdoms, including bacteria, fungi, and viruses. Emerging evidence suggests that the intestinal fungi (the gut "mycobiome") play an important role in host immunity and inflammation. Advances in next generation sequencing methods to study the fungi in fecal samples and mucosa tissues have expanded our understanding of gut fungi in intestinal homeostasis and systemic immunity in health and their contribution to different human diseases. In this review, the current status of gut mycobiome in health, early life, and different diseases including inflammatory bowel disease, colorectal cancer, and metabolic diseases were summarized.

Keywords: Disease; Early life; Gut fungi; Health; Mycobiome.

Figure 1.

The fungal study workflow contains extraction, libraries construction, sequencing, and bioinformatic analysis. (a) Initially DNA/RNA will be isolated from fungal samples. Then DNA or RNA extraction was performed following the protocol of amplicon, metagenomics, and metatranscriptomics according to strategy. Depending on strategy of research, different sequencer is selected from first-generation sequencing to third-generation sequencing. Generally, next generation sequencing (NGS) platform is chosen by higher output like Illumina sequencing by synthesis (SBS) sequencing technology, while-third generation sequencing has also become competitive for sequence full-length small genomes without assembly like Pacbio Single-molecule real-time (SMRT) sequencing. Analyze sequencing data using amplicon, metagenomics, and metatranscriptomics bioinformatics pipeline to analysis 16S rRNA/rDNA, DNA and RNA, respectively. (b) Among the studies involving sequencing methods, there are 10 sequencing platforms are used, in which NGS platform is used frequently and Illumina MiSeq platform is used the most in NGS method. (c) The fungal sequencing strategies are the study of ITS region, analysis of 16S rRNA/rDNA and 18S rRNA/rDNA gene. (d) ITS sequences and commonly and locatable primers used in fungal target region.

Figure 2.

The gut mycobiome through life and the influencing factors in early life. Infants receive mycobiota colonization in the gut at birth, and fungal community increased with age in infancy but decreased when they grow up to young adults. 10 days after birth, Rhodotorula mucilaginosa and Debaryomyces hansenii predominated in the gut of infants, while Candida parapsilosis, C. tropicalis, C. albicans, Saccharomyces cerevisiae, C. orthopsilosis, and Cryptococcus pseudolongus enriched in the anus of infants in the first month. In the adult stage, C. albicans, S. cerevisiae, C. tropicalis, C. glabrata, C. deforans, and Aspergillus glaucus occupy the gut. In later years, Penicillium, Candida, Aspergillus, and Saccharomyces were dominant in the gut of elders. The major factors contributing to neonatal gut fungal communities were mode of feeding and mode of delivery. Compared with neonates by cesarean section, a higher level of Candida and Pleosporales, decreased level of Malassezia were shown in the gut of infants born via vaginal delivery. Moreover, infants could directly acquire mycobiota from breast milk feeding by their mothers, which contains abundant R. mucilaginosa and C. parapsilosis.

Figure 3.

Schematic summary of the gut mycobiome alterations in IBD. Compared with healthy individuals, the gut mycobiome of patients with IBD is characterized by increased fungal diversity and mycobiota dysbiosis accompanying with inflammation. Increased Basidiomycota/Ascomycota ratio and Candida albicans level, decreased proportion of Saccharomyces cerevisiae were shown in the fecal samples of patients with IBD. Similarly, increased fungus load including of C. albicans, C. tropicalis, C. glabrata, and Gibberella moniliformis were also found in the intestinal mucosa of patients with IBD. Nevertheless, pediatric patients with IBD showed a decreased fungal diversity in the gut. C. albicans, C. utilis, C. parapsilosis, S. cerevisiae, Clavispora lusitaniae, and Kluyveromyces marxianus prevailed in the feces of children, while increased abundance of Psathyrellaceae, Cortinariaceae, Psathyrella, and Gymnopilus were detected in their mucosa.