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van Tilburg Bernardes, E.

Publications and source records attributed to van Tilburg Bernardes, E..

2 recordsLinked to original sources

Antibiotic-induced Malassezia spp. expansion in infants promotes early-life immune dysregulation and airway inflammation in mice

Antibiotics have deleterious consequences for the gut microbiome and can increase the risk of childhood asthma. While the effects of antibiotics on the bacterial microbiome and asthma risk are well characterized, their impact on the fungal microbiome (mycobiome) remains vastly unexplored. We investigated the effect of antibiotic use on the gut mycobiome in an observational, prospective clinical study of young infants. Antibiotic treatment resulted in increased fungal abundance and expansion of the yeast Malassezia spp. Based on these findings, germ-free mouse pups were colonized with a defined consortium of mouse-derived bacteria (Oligo-MM12) with or without Malassezia restricta. Colonization with this yeast increased myeloid and lymphoid intestinal immune responses deemed critical in atopy development, and elevated airway inflammation in house-dust mite (HDM)-challenged mice. Further evaluation in eosinophil-deficient mice revealed that the observed immune response is partially dependent on this cell type. This translational work demonstrates that fungal overgrowth and expansion of Malassezia spp. are previously overlooked collateral effects of infant antibiotic use, which may offer a potential strategy to prevent or mitigate pediatric asthma and related conditions. One Sentence Summary: Antibiotic-induced Malassezia spp. expansion in infants promotes early-life immune dysregulation and airway inflammation in gnotobiotic mice.

immunology↗

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

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.

microbiology↗