Impact of glycocalyx shedding and gut microbiota in the exacerbation of asthma induced by obesity

• Grant number: 24/21152-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: April 01, 2025
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Núbia Sabrina Martins
• Supervisor: Timothy Wesley Hand
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Pittsburgh (Pitt), United States
• Associated to the scholarship: 21/14343-3 - Role of chemerin in modulation of lung epithelial and endothelial cells in the comorbidity Asthma and Obesity, BP.DD

Abstract

Obesity is a risk factor to asthma exacerbation. Obese and asthmatic individuals have a poor responsiveness to corticosteroid treatment as consequences of neutrophil and Th17 cell influx to the lungs. Gut dysbiosis is a hallmark of obesity and it is related to asthma susceptibility and exacerbation. Endothelial glycocalyx (EG) is a network of proteoglycans and glycoproteins anchored in endothelial cell membranes. Shedding of EG accentuates the leukocyte-endothelium interaction, increasing leukocyte transmigration and inflammatory response. We fed female C57BL/6 mice during 11 weeks with High Fat Diet (HFD) followed by three intraperitoneal sensitizations with ovalbumin (OVA) plus alum in a 7-day interval and three intranasal challenges in 24-hour intervals. After 48 hours of the last OVA challenge, obese mice showed a significant increase in lung EG shedding compared to mice only exposed to OVA or only fed with HFD. Moreover, obese mice and exposed to OVA had gut dysbiosis, characterized by increase of Romboutsia in the feces. Romboutsia is a Gram-positive anaerobic bacterium related to endothelial function. We hypothesized that obesity-induced dysbiosis, characterized by increase of Romboutsia, induces lung EG shedding after allergen exposure, which results in asthma exacerbation. We aim to investigate the role of Romboutsia using a germ-free like approach with fecal microbiota transplantation and Romboutsia colonization. We expect to identify a potential therapeutic target based on the intervention in EG or in microbiota to improve life quality and to reduce pulmonary inflammation of obese and asthmatic subjects.