Joseph H. Skalski

PurposeThe human microbiome plays a significant role in asthma pathogenesis, with most studies focusing on bacterial communities. This pilot study aims to characterize fungal communities across multiple body sites in asthma patients and identify associations between integrated mycobiome profiles and asthma control.Patients and methodsWe enrolled 24 adults with asthma evaluated at Mayo Clinic between 2020 and 2022. Samples were collected from four body sites (oral wash, nasal swab, sputum, and stool), and fungal communities were characterized using ITS2 sequencing. Multisite mycobiome data were integrated and analyzed using an unsupervised clustering approach. Resulting clusters were compared with respect to fungal composition, site-specific diversity metrics, and asthma control.ResultsTwo patient clusters were identified that differed in asthma control, as measured by the Asthma Control Test (ACT) (p = 0.040). Cluster 1, characterized by poorer asthma control (median ACT score 15.0), demonstrated higher relative abundance of Cladosporium in nasal and sputum samples and greater fungal diversity in sputum compared with Cluster 2 (p = 0.016). Cluster 2, associated with better asthma control (median ACT score 18.4), exhibited higher relative abundance of Candida in stool and sputum samples. No significant differences in fungal diversity were observed in oral, nasal, or stool samples.ConclusionIntegrated multisite mycobiome profiling revealed distinct fungal community patterns associated with asthma control, highlighting the need for larger, longitudinal studies to define their clinical relevance

This review explores the ‘gut–lung axis’ in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community composition alter lung immune function. We comprehensively review available studies that have profiled the composition of the gut mycobiome in adults and children with asthma, and discuss mechanisms of gut–lung interactions that have been described in animal models of asthma. Studies indicate that intestinal fungal dysbiosis, such as an increased abundance of certain fungi like Candida, can elevate the risk of asthma in children and exacerbate it in adults. This effect is mediated through various pathways: the host immune system’s sensing of dysbiosis via C-type lectin receptors (e.g., Dectin-2), the impact of pro-inflammatory fungal metabolites (e.g., 12,13-diHOME, prostaglandin E2), and the role of lung immune cells (e.g., group 2 innate lymphoid cells [ILC2], M2 macrophages). We also describe strategies for modulating the gut mycobiome as potential therapies for severe asthma. The review concludes by emphasizing the necessity for further research into the role of the gut mycobiome in asthma to deepen our understanding of these complex interactions.

Overgrowth of the fungus Wallemia mellicola in the intestines of mice enhances the severity of asthma. Wallemia mellicola interacts with the immune system through Dectin-2 expressed on the surface of myeloid and intestinal epithelial cells. Using Dectin-2-deficient mice, we show that the interaction of W. mellicola with Dectin-2 is essential for the gut-lung pathways, enhancing the severity of asthma in mice with W. mellicola intestinal dysbiosis. These findings offer better insight into dysbiosis-associated inflammation and highlight the role pattern recognition receptors have in immune recognition of commensal fungi in the gut, leading to alterations in immune function in the lungs.

Background: The gut-lung axis is the concept that alterations of gut microbiota communities can influence immune function in the lungs. While studies have explored the relationship between intestinal bacterial dysbiosis and asthma development, less is understood about the impact of commensal intestinal fungi on asthma severity and control and underlying mechanisms by which this occurs. Methods: Wild-type mice were treated with Cefoperazone to deplete gut bacteria and administered Candida albicans or water through gavage. Mice were then sensitized to house dust mite (HDM) and their lungs were analyzed for changes in immune response. Humans with asthma were recruited and stool samples were analyzed for Candida abundance and associations with asthma severity and control. Results: Mice with intestinal Candida dysbiosis had enhanced Th2 response after airway sensitization with HDM, manifesting with greater total white cell and eosinophil counts in the airway, and total IgE concentrations in the serum. Group 2 innate lymphoid cells (ILC2) were more abundant in the lungs of mice with Candida gut dysbiosis, even when not sensitized to HDM, suggesting that ILC2 may be important mediators of the enhanced Th2 response. These effects occurred with no detectable increased Candida in the lung by culture or rtPCR suggesting gut-lung axis interactions were responsible. In humans with asthma, enhanced intestinal Candida burden was associated with the risk of severe asthma exacerbation in the past year, independent of systemic antibiotic and glucocorticoid use. Conclusions: Candida gut dysbiosis may worsen asthma control and enhance allergic airway inflammation, potentially mediated by ILC2. Further studies are necessary to examine whether microbial dysbiosis can drive difficult-to-control asthma in humans and to better understand the underlying mechanisms.

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. The microbiome is the ecosystem of bacteria, fungi, viruses, and other microorganisms that live in and on us. The intestines are where most of these organisms reside, and the composition of the intestinal microbiota has a profound effect on immune system function throughout the body. In this manuscript, 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. After expansion of this fungal population, the mice are more prone to develop asthma-like inflammation in their lungs when exposed to allergens. Although it is not known whether the same phenomenon can occur in people with asthma, we have also identified this fungus as a component of the microbiota of some healthy humans. Elimination of this organism from the intestines is not as simple as taking an antifungal medication because antifungal medications can also disrupt the balance of the intestinal microbial community and may similarly worsen allergic airways disease.

Rationale: The implementation of team-based care models in residency programs is one method to improve patient and provider outpatient satisfaction. However, to our knowledge, this has not yet been studied in fellowship programs. Objectives: We instituted a pilot project to test a team-based model of care in our pulmonary and critical care medicine (PCCM) fellows’ clinic by creating a new outpatient role called the “Fellow of the Day,” with the goal of reducing clinical disruption for the fellows, providing more educational value for medical students, and improving patient care. Methods: Data were collected over a 4-month time period from electronic surveys from medical students, fellows, and supervising faculty. We also used timestamp data to determine fellows’ response times to patient messages. Results: After implementation of the Fellow of the Day designation, (1) fellows were more engaged in teaching the medical student (P = 0.007); (2) fellows spent less of their personal time (P = 0.04) or time away from critically ill patients to focus on patient care–related messages (P = 0.04) and paperwork (P = 0.02); and (3) medical students had improved experience with more enjoyment (P = 0.03) and active engagement in clinic (P = 0.03). The Fellow of the Day role did not affect faculty workflow. Patients received responses to their postvisit messages in a more timely manner (P = 0.003). Conclusions: The Fellow of the Day role was successfully implemented at our institution with multiple benefits, not only to fellows but also to patients, medical students, and supervising faculty. Our education committee has recommended continuation of the role in our fellowship program.

Background : The interview visit is an important component of residency and fellowship recruitment that requires a substantial expenditure of time and resources for both training programs and candidates. Objective : Survey aimed to study the impact of a preinterview dinner on fellowship program candidates. Methods : A single center preintervention and postintervention comparison study was conducted using an electronic survey distributed to all Pulmonary and Critical Care Fellowship candidates over 3 years (2013–2015). The interview visit in 2013 did not include a preinterview dinner (no-dinner group), while the candidates interviewing in 2014 and 2015 were invited to a preinterview dinner with current fellows on the evening before the interview day (dinner group). Results : The survey was distributed to all candidates (N = 70) who interviewed between 2013 and 2015 with a 59% (n = 41) completion rate. Ninety percent of respondents (37 of 41) reported that a preinterview dinner is valuable, primarily to gain more information about the program and to meet current fellows. Among candidates who attended the dinner, 88% (23 of 26) reported the dinner improved their impression of the program. The dinner group was more likely to have a positive view of current fellows in the program as desirable peers compared to candidates in the no-dinner group. Conclusions : This pilot study suggests that a preinterview dinner may offer benefits for candidates and training programs and may enhance candidates' perceptions of the fellowship program relative to other programs they are considering.