Maturational patterns of the infant gut mycobiome are associated with early-life body mass index.

Unlike the bacterial microbiome, the role of early-life gut fungi in host metabolism and childhood obesity development remains poorly characterized. To address this, we investigate the relationship between the gut mycobiome of 100 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study and body mass index Z scores (BMIz) in the first 5 years of life. An increase in fungal richness during the first year of life is linked to parental and infant BMI. The relationship between richness pattern and early-life BMIz is modified by maternal BMI, maternal diet, infant antibiotic exposure, and bacterial beta diversity. Further, the abundances of Saccharomyces, Rhodotorula, and Malassezia are differentially associated with early-life BMIz. Using structural equation modeling, we determine that the mycobiome's contribution to BMIz is likely mediated by the bacterial microbiome. This demonstrates that mycobiome maturation and infant growth trajectories are distinctly linked, advocating for inclusion of fungi in larger pediatric microbiome studies.

"Molding" immunity-modulation of mucosal and systemic immunity by the intestinal mycobiome in health and disease.

Fungi are important yet understudied contributors to the microbial communities of the gastrointestinal tract. Starting at birth, the intestinal mycobiome undergoes a period of dynamic maturation under the influence of microbial, host, and extrinsic influences, with profound functional implications for immune development in early life, and regulation of immune homeostasis throughout life. Candida albicans serves as a model organism for understanding the cross-talk between fungal colonization dynamics and immunity, and exemplifies unique mechanisms of fungal-immune interactions, including fungal dimorphism, though our understanding of other intestinal fungi is growing. Given the prominent role of the gut mycobiome in promoting immune homeostasis, emerging evidence points to fungal dysbiosis as an influential contributor to immune dysregulation in a variety of inflammatory and infectious diseases. Here we review current knowledge on the factors that govern host-fungi interactions in the intestinal tract and immunological outcomes in both mucosal and systemic compartments.

The intestinal mycobiome as a determinant of host immune and metabolic health.

The inclusion of fungi in recent human and animal microbiome studies has revealed that microbiome features associated with health or disease are not exclusively bacterial. Factors known to impact bacterial microbiome development, such as gestational age at birth, breast feeding status and antibiotics also impact the mycobiome. Strong inter-kingdom interactions take place in the luminal gut, and while the mycobiome exhibits increased inter-individual variability, certain fungi are stable colonizers. Here, we review recent studies showing that the gut mycobiome also plays an important role in disease states related to host immunity and energy metabolism. Some persistent species, such as Candida sp., as well as other less stable colonizers have been shown to play an important role in host-mycobiome immune cross talk. Mechanisms by which gut fungi interact with immune development have begun to be elucidated yet the majority remain elusive. Further investigation into these immune and metabolic mechanisms hold great potential for novel discoveries and will provided a much needed multi-kingdom understanding of the microbiome's influence on host health.

The Fungal Microbiome and Asthma.

Asthma is a group of inflammatory conditions that compromises the airways of a continuously increasing number of people around the globe. Its complex etiology comprises both genetic and environmental aspects, with the intestinal and lung microbiomes emerging as newly implicated factors that can drive and aggravate asthma. Longitudinal infant cohort studies combined with mechanistic studies in animal models have identified microbial signatures causally associated with subsequent asthma risk. The recent inclusion of fungi in human microbiome surveys has revealed that microbiome signatures associated with asthma risk are not limited to bacteria, and that fungi are also implicated in asthma development in susceptible individuals. In this review, we examine the unique properties of human-associated and environmental fungi, which confer them the ability to influence immune development and allergic responses. The important contribution of fungi to asthma development and exacerbations prompts for their inclusion in current and future asthma studies in humans and animal models.

Intestinal fungi are causally implicated in microbiome assembly and immune development in mice.

The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, susceptibility to colitis, and airway inflammation. Fungal colonization promotes major shifts in bacterial microbiome ecology, and has an independent effect on innate and adaptive immune development in young mice. While exclusive fungal colonization is insufficient to elicit overt dextran sulfate sodium-induced colitis, bacterial and fungal co-colonization increase colonic inflammation. Ovalbumin-induced airway inflammation reveals that bacterial, but not fungal colonization is necessary to decrease airway inflammation, yet fungi selectively promotes macrophage infiltration in the airway. Together, our findings demonstrate a causal role for fungi in microbial ecology and host immune functionality, and therefore prompt the inclusion of fungi in therapeutic approaches aimed at modulating early life microbiomes.