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ABSTRACT Acute respiratory distress syndrome (ARDS) is an often fatal critical illness where lung epithelial injury leads to intrapulmonary fluid accumulation. ARDS became widespread during the COVID-19 pandemic, motivating a renewed effort to understand the complex etiology of this disease. Rigorous prior work has implicated lung endothelial and epithelial injury in response to an insult such as bacterial infection; however, the impact of microorganisms found in other organs on ARDS remains unclear. Here, we use a combination of gnotobiotic mice, cell culture experiments, and re-analyses of a large metabolomics dataset from ARDS patients to reveal that gut bacteria impact lung cellular respiration by releasing metabolites that alter mitochondrial activity in lung epithelium. Colonization of germ-free mice with a complex gut microbiota stimulated lung mitochondrial gene expression. A single human gut bacterial species,Bifidobacterium adolescentis,was sufficient to replicate this effect, leading to a significant increase in mitochondrial membrane potential in lung epithelial cells. We then used genome sequencing and mass spectrometry to confirm thatB. adolescentisproducesL-lactate, which was sufficient to increase mitochondrial activity in lung epithelial cells. Finally, we found that serum lactate was significantly associated with disease severity in patients with ARDS from the Early Assessment of Renal and Lung Injury (EARLI) cohort. Together, these results emphasize the importance of more broadly characterizing the microbial etiology of ARDS and other lung diseases given the ability of gut bacterial metabolites to remotely control lung cellular respiration. Our discovery of a single bacteria-metabolite pair provides aproof-of-conceptfor systematically testing other microbial metabolites and a mechanistic biomarker that could be pursued in future clinical studies. Furthermore, our work adds to the growing literature linking the microbiome to mitochondrial function, raising intriguing questions as to the bidirectional communication between our endo- and ecto-symbionts. 

ABSTRACT We previously developed and assessed “The Art of Microbiology,” a course-based undergraduate research experience (CURE) which uses agar art to spur student experimentation, where we found student outcomes related to science persistence. However, these outcomes were not correlated with specific activities and gains were not reported from more than one class. In this study, we explored which of the three major activities in this CURE—agar art, experimental design, or poster presentations—affected student engagement and outcomes associated with improved understanding of the nature of science (NOS). The Art of Microbiology was studied in three microbiology teaching laboratories: at a research university with either the CURE developer (18 students) or a CURE implementer (39 students) and at a community college with a CURE implementer (25 students). Our quasi-experimental mixed methods study used pre/post-NOS surveys and semi-structured class-wide interviews. Community college students had lower baseline NOS responses but had gains in NOS similar to research university students post-CURE. We surveyed research university students following each major activity using the Assessing Student Perspective of Engagement in Class Tool (ASPECT) survey but did not find a correlation between NOS and activity engagement. Of the three activities, we found the highest engagement with agar art, especially in the CURE developer class. Interviewed students in all classes described agar art as a fun, relevant, and low-stakes assignment. This work contributes to the evidence supporting agar art as a curricular tool, especially in ways that can add research to classrooms in and beyond the research university.