Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice

Abstract

Gut microbiomes make major contributions to the physiological and immunological development of the host, but the relative importance of their bacterial and fungal components, and how they interact, remain largely unknown. We applied carefully controlled experiments in gnotobiotic mice colonized with defined communities of bacteria, fungi, or both to differentiate the direct role of fungi on microbiome assembly, host development, and susceptibility to colitis and airway inflammation. Our results revealed that fungal colonization alone was insufficient to promote the intestinal anatomic and physiological changes seen in mice colonized by bacteria, and had limited impact on the fecal metabolome. However, fungal colonization promoted major shifts in bacterial microbiome ecology, and had an independent effect on the innate and adaptive immune development in young mice. Fungi further exacerbated some aspects of the inflammatory effects of the bacterial community during OVA-induced airway inflammation by promoting macrophage infiltration in the airway. Our results demonstrate a dominant ecological and physiological role of bacteria in gut microbiomes, but highlight fungi as an ecological factor shaping the assembly of the bacterial community and a direct capacity to impact immune system and modulate disease susceptibility. These findings demonstrate that studies focused on bacteria alone provide an incomplete portrayal on microbiome ecology and functionality, and prompt for the inclusion of fungi in human microbiome studies.