Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease

Abstract

Human holobiomes are networks of mutualistic interactions between human cells and complex communities of bacteria and fungi that colonize the human body. The immune system must tolerate colonization with commensal bacteria and fungi but defend against invasion by either organism. Molecular ecological surveys of the human prokaryotic microbiota performed to date have revealed a remarkable degree of bacterial diversity and functionality. However, there is a dearth of information regarding the eukaryotic composition of the microbiota. In this review, we describe the ecology and the human niches of our fungal "fellow travelers" in both health and disease, discriminating between passengers, colonizers, and pathogens based on the interaction of these fungi with the human immune system. We conclude by highlighting the need to reconsider the etiology of many fungal and immune-related diseases in the context of the crosstalk between the human system and its resident microbial communities.Keywords: Dysbiosis r Fungal metagenomics r Host-microbe interaction r Mycobiota IntroductionHumans live in close association with a complex community of bacteria, viruses, fungi, and archaea [1][2][3], which inhabit their bodies. Many groups have surveyed these microbial populations using the so-called "next generation" or "deep" sequencing approaches, revealing that the human microbiota differs radically at various body sites and among individuals [2][3][4]. The differences in the human microbiota are influenced by the availability of nutrients, environmental exposure to microorganisms, and other sitespecific features, such as the immunological makeup of a given location. The origin of differences in the microbiota between individuals potentially reflects different patterns of colonization early in life (reviewed in [5]), different dietary regimens [6,7], and different environmental exposures, such as antibiotic use [8,9]. Recently, the application of deep sequencing approaches have genCorrespondence: Dr. Duccio Cavalieri e-mail: duccio.cavalieri@fmach.it erated novel hypotheses about the microbial determinants underlying human disorders of immune origin (reviewed in [10]). Several metabolites of the interaction between diet and host microbiota, such as short-chain fatty acids, have been shown to play a fundamental role in shaping immune responses (reviewed in [11]). The application of microbial ecology concepts is ultimately leading to the conclusion that health and disease can be understood only through an understanding of the ways in which the symbiotic interactions between microbes and human organs harmonically integrate in the context of the hologenome [12].Human microbial diversity is not limited to bacteria; microorganisms such as fungi also play major roles in the stability of microbial communities in human health and disease (reviewed in [13]). Yeasts were detected in human stool samples as far back as 1917, and by the mid-20th century the presence of yeasts in the human intestine was proposed to have a saprotrophic role [14]....

The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases

“…126,127 Concerted effort, such as that given to surveying bacterial composition and abundance, is required to carry this field into the translational and clinical arenas. Characterization of the human mycobiome has the potential to produce widespread clinical advances in diagnosis, treatment and prevention of fungal infections 23,128 and vulvovaginal candidiasis, in particular, but also potentially bacterial and viral infections.…”

Colonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life

“…Eukaryotes and microeukaryotes, which form part of the human microbiota, have been shown to exert immunomodulatory effects on the host (Weinstock, 2012; Rizzetto et al, 2014). Furthermore, infections by parasitic eukaryotes have been linked to decreased allergic and autoimmune disease prevalence (Weinstock, 2012) and have been used for therapeutic interventions in that context (McFarland and Bernasconi, 1993; Williamson et al, 2016).…”

Effects of hemin, CO2, and pH on the branching of Candida albicans filamentous forms

“…albicans, a wide-spread commensal pathogen of humans, has the capability to colonize or even invade a number of anatomical niches within the human body [1,46]. It is well documented that the proper timing and the rate of Y → H and H → Y morphological transitions are the prerequisites of a successful invasion of the host by C. albicans [35,36,39,47].…”

“…These observations on hyphal branching inspired us to set up the following hypotheses, which may provide us with suitable models to answer the intriguing question that how C. albicans, which inhabits so many anatomical niches within the human body, can cause various types of candidiasis [1,46].…”

“…The dimorphic fungus Candida albicans is a commensal microorganism, which has been identified in healthy mycobiomes of the human skin, mouth, and gut [1]. In addition, Candida species with the predominance of C. albicans also appeared in 64.5% of reproductive-age asymptomatic women as part of their vaginal mycobiome [2].…”