Abstract
The gastrointestinal microbiota influences immune function throughout the body. The gut-lung axis refers to the concept that alterations of gut commensal microorganisms can have a distant effect on immune function in the lung. Overgrowth of intestinal Candida albicans has been previously observed to exacerbate allergic airways disease in mice, but whether subtler changes in intestinal fungal microbiota can affect allergic airways disease is less clear. In this study we have investigated the effects of the population expansion of commensal fungus Wallemia mellicola without overgrowth of the total fungal community. Wallemia spp. are commonly found as a minor component of the commensal gastrointestinal mycobiota in both humans and mice. Mice with an unaltered gut microbiota community resist population expansion when gavaged with W. mellicola; however, transient antibiotic depletion of gut microbiota creates a window of opportunity for expansion of W. mellicola following delivery of live spores to the gastrointestinal tract. This phenomenon is not universal as other commensal fungi (Aspergillus amstelodami, Epicoccum nigrum) do not expand when delivered to mice with antibiotic-depleted microbiota. Mice with Wallemia-expanded gut mycobiota experienced altered pulmonary immune responses to inhaled aeroallergens. Specifically, after induction of allergic airways disease with intratracheal house dust mite (HDM) antigen, mice demonstrated enhanced eosinophilic airway infiltration, airway hyperresponsiveness (AHR) to methacholine challenge, goblet cell hyperplasia, elevated bronchoalveolar lavage IL-5, and enhanced serum HDM IgG1. This phenomenon occurred with no detectable Wallemia in the lung. Targeted amplicon sequencing analysis of the gastrointestinal mycobiota revealed that expansion of W. mellicola in the gut was associated with additional alterations of bacterial and fungal commensal communities. We therefore colonized fungus-free Altered Schaedler Flora (ASF) mice with W. mellicola. ASF mice colonized with W. mellicola experienced enhanced severity of allergic airways disease compared to fungus-free control ASF mice without changes in bacterial community composition.
Highlights
The gut microbiome is a dynamic ecosystem that profoundly influences immune function throughout the body [1,2,3]
We observe that expansion of a certain species of house dust fungus (Wallemia mellicola) can occur in the intestines of mice after they are treated with antibiotics and exposed to the fungus, but that mice with an intact and healthy intestinal microbiota resist this expansion
We examined conditions required for enhancing intestinal colonization with several non-Candida commensal fungal species that are natively found in the intestinal microbiota of specific pathogen free mice (SPF) at our animal facility: Wallemia mellicola, Aspergillus
Summary
The gut microbiome is a dynamic ecosystem that profoundly influences immune function throughout the body [1,2,3]. The commensal microbial composition of the gut can have a distant effect on immune function in the lung and other organ systems; this is the concept of the gut-lung axis. The healthy gastrointestinal system contains a community of commensal fungi that live in the gut and continually interact with the gastrointestinal mucosa [8,9,10]. There are several sample processing and analysis considerations distinct from 16S analysis, ITS1 sequencing has been used successfully to profile gastrointestinal fungal communities in a both mice and humans [9, 11]. Studies using ITS1 sequencing to profile the human gastrointestinal mycobiota generally report a diverse community containing more than 50 unique genera with substantial variation across individuals [8]
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