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Changes in maternal gut microbiota induced by fructose consumption during pregnancy: implications for the inflammatory allergic airway response in the offspring

Grant number: 21/06444-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2021
Effective date (End): July 31, 2022
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Silvana Auxiliadora Bordin da Silva
Grantee:Amanda Santos Cavalcante
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Consumption of beverages artificially sweetened with fructose has been increasing in Western society since the 1970s. In parallel to this eating behavior, recent epidemiological data show an increase in the incidence of asthma in children born to mothers who consume excessive amounts of fructose-sweetened drinks during pregnancy. Despite this epidemiological correlation, it has not been experimentally tested whether fructose consumption during pregnancy programs the allergic inflammatory response in the airway of the offspring. This demonstration becomes relevant because consuming soft drinks and sweetened beverages is frequently confounded by a number of other factors that may contribute to the allergic inflammatory response, such as the reduction in fiber intake from vegetables, fruits and cereals. It is known that eating a diet devoid of fiber during pregnancy leads to an exacerbation of allergic asthma in the offspring, which may be associated to changes in the composition and function of maternal intestinal microbiota. Thus, the primary objective of this project is to determine if fructose consumption during pregnancy is associated with changes in the composition and function of maternal intestinal microbiota, which in turn, exacerbates the inflammatory response of allergic asthma in the offspring. To achieve this goal, we will expose C57BL/6N mice to fructose (10% in drinking water) during pregnancy and assess multiple parameters of both the mothers and offspring. The offspring will be submitted to the ovalbumin (OVA) sensitization/challenge model to evaluate the allergic airway response. The concentrations of IL-4, IL-5, IL-10 and IL-13 in the bronchoalveolar lavage (BAL) and serum IgE will be evaluated. Eosinophil infiltration, collagen deposition and mucus production in the lung and the taxonomic composition and predicted function of the airway microbiota will also be evaluated. The taxonomic profile of the maternal gut microbiota will be evaluated by 16s rRNA sequencing and its potential to activate asthma-linked immune responses will be assessed by TLR4 and NOD2 activation in vitro. It will also be evaluated whether fructose consumption during pregnancy changes maternal gut permeability and mucus production in the gut and lungs. This proposal also aims to evaluate whether dietary supplementation with complex carbohydrates with prebiotic functions (galacto-oligosaccharide and fructo-oligosaccharide - GOS and FOS) during pregnancy can prevent phenotypic changes induced by fructose in mothers and in the offspring. Finally, we will empirically test the role of fructose-induced changes in the gut microbiota by colonizing germ free C57BL/6N female mice with the microbiota from mice that drank fructose versus only water. We will breed these newly colonized mice and assess the allergic response in offspring, using the parameters described above. Altogether, the experimental design currently proposed will test the hypothesis that changes in maternal gut microbiota caused by excessive fructose consumption during pregnancy may lead to exacerbation of allergic airway disease in offspring. (AU)

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