Personalized probiotic therapy efficacy in reducing the risk of Dysbiosis-related diseases

• Grant number: 19/13942-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2020
• End date: March 31, 2023
• Field of knowledge: Health Sciences - Nutrition
• Principal Investigator: Daniela Cardoso Umbelino Cavallini
• Grantee: Daniela Cardoso Umbelino Cavallini
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Alexandra Ivo de Medeiros ; Larissa Sbaglia Celiberto ; Luis Carlos Spolidorio

Abstract

There is a complex relationship between the intestinal microbiota and the homeostasis of the immune system and the alteration in its composition is involved in the genesis of different inflammatory diseases. Ingestion of probiotics microorganisms have been used to beneficially modify the microbiota of individuals with chronic diseases. However, such approaches have limitations, such as intestinal microbiota resilience, patient acceptance, and the discrepancy of results obtained in clinical studies. Considering the specificity of the human microbiota, the objective of the present study is to obtain a personalized (individualized) probiotic cell bank as well as to evaluate the effect of this approach in the prevention and treatment of Dysbiosis-related diseases. The project will be divided into three subprojects: A) Optimization of the selection of potentially probiotic strains for personalized therapy in children; B) Evaluation of the effect of personalized therapy in the prevention of relapses of colitis induced by Dextran Sulfate Sodium (DSS); C) Evaluation of the effect of personalized therapy on the treatment of obesity and its consequences. In subproject A, the isolation and characterization of bacterial strains will be performed for the personalized treatment in subprojects B and C. Strains will be isolated from fecal material of each donor by plating in selective media and characterized by RAPD-PCR, Gram staining, antibiotic resistance test and sequencing (Illumina Mi Seq). The selected strains (especially Lactobacillus spp. and Bifidobacterirum spp.) will be stored in an individualized microbiota bank. The experiments in animal models (subprojects B and C) will be conducted in specific pathogen free Swiss (Unib: SW) mice (n = 10), which will initially receive a cocktail of antibiotics to deplete their resident microbiota and then will be recolonized with the microbiota of subproject A volunteers (one volunteer will donate fecal material to colonize two animals from each experiment). After the induction of colitis (DSS - 3%) and obesity (hyperlipidic diet), the animals will be treated with strains isolated from fecal samples used for microbiota recolonization (personalized treatment).The parameters to be evaluated include: weight variation, fecal microbiota composition (sequencing), cytokine profile (ELISA) and others inflammatory markers, histological changes (colon and adipocytes) and short chain fatty acid profile. Therefore, this project intends to show that the restoration of the commensal microbiota is able to reduce the symptoms and the development of diseases which genesis includes Dysbiosis and that the effectiveness of the personalized therapy with probiotics presents superior effects in comparison with the traditional approach. (AU)