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Investigating the impact of fructose consumption on the airway inflammatory response during allergic asthma: focus on the gut microbiota

Grant number: 19/17953-7
Support type:Scholarships abroad - Research
Effective date (Start): August 06, 2020
Effective date (End): February 05, 2021
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Gabriel Forato Anhê
Grantee:Gabriel Forato Anhê
Host: Jonathan Schertzer
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Local de pesquisa : McMaster University, Canada  
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Recent epidemiological data reveled that excessive consumption of fructose-sweetened beverages correlate with a higher risk for asthma in infants and adults. To date, however, no experimental evidence supports that fructose consumption exacerbates inflammatory response in allergic asthma. The latter is hallmarked by a predominant TH2 activation in which key cytokines, such as IL-4, IL-5, IL-10 and IL-13, lead to IgE production and eosinophil infiltration in the lung parenchyma. This response is modulated by pattern-recognition receptors (PRR) such as TLR4 and NOD2. Noteworthy, experimental models of metabolic syndrome induced by excessive fructose ingestion are known to drive changes in the gut microbiota that parallel increased intestinal permeability and metabolic endotoxemia. The aim of this project is to determine whether fructose consumption exacerbates the airway inflammatory response in mice subjected to the Ovalbumin (OVA) sensitization/challenge model of allergic asthma. We also aim to establish whether such putative effects of fructose consumption are linked to changes in the gut microbiota. To achieve these goals, male C57BL/6 mice will be treated with fructose, glucose or sucrose in the drinking water. Additional positive and negative control groups will consist of the combination of either prebiotics or antibiotics to liquid fructose. Treatments will be carried out for 8 weeks and sensitization/challenge with OVA will occur during the last 2 weeks. We will determine the levels of TH2 interleukins (IL-4, IL-5, IL10 and IL-13) and the counts of eosinophils and neutrophils in bronchoalveolar lavage (BAL) samples. Gut microbiota from fecal samples will be profiled by 16S rRNA gene sequencing. Gut microbiota from fecal slurries and serum from portal blood will be used in vitro to determine the gut microbial capacity to activate TLR4 and NOD2.