Glucagon-Like Peptide 1 Receptor (<i>Glp1r</i>) Deficiency Does Not Appreciably Alter Airway Inflammation or Gut-Lung Microbiome Axis in a Mouse Model of Obese Allergic Airways Disease and Bariatric Surgery.
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2025-01
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High body mass index (≥30 kg/m2) is associated with asthma severity, and nearly 40% of asthma patients exhibit obesity. Furthermore, over 40% of patients with obesity and asthma that receive bariatric surgery no longer require asthma medication. Increased levels of glucagon-like peptide 1 (GLP-1) occur after bariatric surgery, and recent studies suggest that GLP-1 receptor (GLP-1R) signaling may regulate the gut microbiome and have anti-inflammatory properties in the lung. Thus, we hypothesized that increased GLP-1R signaling following metabolic surgery in obese and allergen-challenged mice leads to gut/lung microbiome alterations, which together contribute to improved features of allergic airways disease.Methods
Male and female Glp1r-deficient (Glp1r-/- ) and replete (Glp1r+/+) mice were administered high fat diet (HFD) to induce obesity with simultaneous intranasal challenge with house dust mite (HDM) allergen to model allergic airway disease with appropriate controls. Mice on HFD received either no surgery, sham surgery, or vertical sleeve gastrectomy (VSG) on week 10 and were sacrificed on week 13. Data were collected with regard to fecal and lung tissue microbiome, lung histology, metabolic markers, and respiratory inflammation.Results
HFD led to metabolic imbalance characterized by lower GLP-1 and higher leptin levels, increased glucose intolerance, and alterations in gut microbiome composition. Prevalence of bacteria associated with short chain fatty acid (SCFA) production, namely Bifidobacterium, Lachnospiraceae UCG-001, and Parasutterella, was reduced in mice fed HFD and positively associated with serum GLP-1 levels. Intranasal HDM exposure induced airway inflammation. While Glp1r-/- genotype affected fecal microbiome beta diversity metrics, its effect was limited.Conclusion
Herein, GLP-1R deficiency had surprisingly little effect on host gut and lung microbiomes and health, despite recent studies suggesting that GLP-1 receptor agonists are protective against lung inflammation.Type
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Kim, Yeon Ji, Victoria M Ihrie, Pixu Shi, Mark D Ihrie, Jack T Womble, Anna Hill Meares, Joshua A Granek, Claudia K Gunsch, et al. (2025). Glucagon-Like Peptide 1 Receptor (<i>Glp1r</i>) Deficiency Does Not Appreciably Alter Airway Inflammation or Gut-Lung Microbiome Axis in a Mouse Model of Obese Allergic Airways Disease and Bariatric Surgery. Journal of asthma and allergy, 18. pp. 285–305. 10.2147/jaa.s478329 Retrieved from https://hdl.handle.net/10161/32525.
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Scholars@Duke
Pixu Shi
Joshua Aaron Granek
We have broad interests in using microbial genomics to understand how microbes interact with each other and their hosts. This interest includes the roles played by both beneficial and harmful bacteria, fungi, and viruses and how they interact with the immune system. We study single microbes and microbial communities, primarily using high-throughput sequencing methods. We have a particular interest in developing new experimental and analytical methods that leverage the power of high-throughput sequencing. We are also interested in using deep learning in microbiology research.
Claudia K. Gunsch
Claudia Gunsch is a Professor of Civil and Environmental Engineering and holds secondary appointments in the Nicholas School of the Environment and the Department of Biomedical Engineering. She joined the Duke Faculty in 2004 after obtaining her PhD from the University of Texas at Austin, her MS from Clemson University and her BS from Purdue University. Currently, she serves as the Director for PreMiEr, the National Science Foundation Engineering Research Center for Precision Microbiome Engineering which is a joint venture between Duke University, North Carolina A&T State University, North Carolina State University, the University of North Carolina – Chapel Hill and the University of North Carolina – Charlotte. She also serves as an Associate Director for the Duke Microbiome Center. Previous leadership roles include serving as Associate Dean for Research and Infrastructure for the Pratt School of Engineering (2021-2022), Associate Vice Provost for Faculty Advancement (2019-2021) and as the Director of IBIEM (Integrative Bioinformatics for Investigating and Engineering Microbiomes), a joint graduate training program between Duke and North Carolina A&T State University (2015-2021).
Dr. Gunsch’s research bridges environmental engineering and molecular biotechnology. Current research foci include investigating the ecological impacts of emerging contaminants on environmental microbiomes, developing microbiome engineering approaches for bioremediation, studying microbial evolution following exposure to anthropogenic contaminants and developing innovative water treatment technologies. Her work has been funded in excess of $36 million by the National Science Foundation, US Environmental Protection Agency, National Institute for Environmental Health and Safety as well as state funding agencies and private industry. Since becoming a faculty member, she has served as the primary mentor for 28 graduate students (8 MS and 20 PhD), 34 undergraduate students and 8 postdoctoral associates. She has been recognized for her research, teaching and service activities with several awards including the 2009 National Science Foundation Faculty Early Career Development Award, 2013 Langford Lectureship Award, 2016 Capers and Marion McDonald Award for Excellence in Mentoring and Advising and the 2016 American Society of Civil Engineers (ASCE) Walter L. Huber Civil Engineering Research Prize. Dr. Gunsch was also named ASCE Environmental & Water Resources Institute Fellow in 2022, Bass Fellow in 2016 and Fellow of the National Academy of Engineering for the United States Frontiers of Engineering in 2011 as well as the Indo-American Frontiers of Engineering in 2014.
She currently serves as Editor in Chief for Biodegradation. She is also a member of the Editorial Board for npj Clean Water and Industrial Biotechnology. She serves on the Association of Environmental Engineering and Science Professors (AEESP) Board of Directors and has previously held several leadership roles within the Environmental & Water Resources Institute (EWRI). Most recently, she served as the Environmental Council representative to the Technical Executive Committee to EWRI.
Jennifer Leigh Ingram
Dr. Ingram's research interests focus on the study of airway remodeling in human asthma. Proliferation, migration, and invasion of airway fibroblasts are key features of airway remodeling that contribute to diminished lung function over time. Dr. Ingram uses molecular biology approaches to define the effects of interleukin-13 (IL-13), a cytokine abundantly produced in the asthmatic airway, in the human airway fibroblast. She has identified important regulatory functions of several proteins prevalent in asthma that control fibroblast growth and pro-fibrotic growth factor production in response to IL-13. By understanding these pathways and their role in human asthma and the chronic effects of airway remodeling, novel treatment strategies may be developed.
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