Chagasic Megacolon: study of the intestinal microbioma and genetic profile of Trypanosoma cruzi by next generation sequencing

• Grant number: 23/01881-2
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2023 - August 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Sandra Cecília Botelho Costa
• Grantee: Sandra Cecília Botelho Costa
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Andrey dos Santos ; Claudio Saddy Rodrigues Coy ; Daniéla Oliveira Magro ; Eros Antonio de Almeida ; Gláucia Elisete Barbosa Marcon ; Luiz Cláudio Martins ; Mario Jose Abdalla Saad

Abstract

Chagas disease is a social and economic problem in many countries of the Latin America, affeting 6 to 7 million people. The acute phase, after the infection happens in a few days, and may even be asymptomatic, then the patient progresses to the chronic phase, which mostly remains in the indeterminate form, about 30% develop the cardiac form and approximately 10% to 15 % develop the digestive form. The geographic distribution of the clinical forms is associated with parasite genetic profile, identified by the isolation of the parasite in the blood, followed by molecular techniques for the classification in discrete typing units (DTUs). Next-generation sequencing (NGS) of the mini-éxon region, directly from biological material has been shown to be a useful tool for the identification of DTUs, without going through isolation in culture. Chagasic megaesophagus and megacolon occur due to denervation and decreased peristalsis. Palliative treatment for megaesophagus is surgical. In megacolon, is done with the ingestion of fibers and in advanced cases, organ resection surgery is necessary. Studies have demonstrate that the intestinal microbiota play an important role in the pathogenesis in cardiac and digestive forms, and may be involved in the host response. Through the NGS of the 16S rRNA region of the genetic material obtained from feces, it was observed that the dysbiosis can influence the disease pathogenesis. Our hypothesis is that in patients with megacolon, DNA sequencing of the intestinal tissue will have similar genetic profiles directly associated with the digestive form. Another hypothesis associated with Chagas disease pathogenesis is about the difference and quality of the microbiome found in patients with chagasic and no-chagasic megacolon, what determine the impact on the disease progression. Therefore, we intend to test our hypothesis by verifying the DTUs by sequencing of the mini-exon region of the T. cruzi, directly of the extracted DNA from the gastrointestinal tissue of patients with chagasic megacolon, as well to study the intestinal microbiota in patients with megacolon and to verify the difference between the bacterial populations and their relationship to megacolon. This will be a multicentric study, in which will be involved experientes researchers of the infectology, gastric surgery and molecular biology of the importante institution (University of Campinas - Unicamp and Oswaldo Cruz Foundation - Fiocruz) in order to contribute to the aspects related to the pathogenesis of Chagas disease. The project will have as a proponent, Dr Sandra C. B. Costa, responsible for the Laboratory of Diagnosis of Infectious Diseases by Molecular Biology Techniques (LDITBIM) and professor at the Department of Internal Medicine, Faculty of Medical Sciences, UNICAMP. The team will include Dr Gláucia E B Marcon, a researcher in Public Health at the Oswaldo Cruz Foundation (FIOCRUZ), Dr Eros Almeida, Dr Luiz Cláudio Martins, both from the Chagas Disease Study Group (GEDoCh) and professors from the Department of Clinical Physician, FCM/UNICAMP, in addition to Dr Cláudio Coy, Dr Mario Saad, Dr Andrey Santos, Dr Daniela Oliveira Magro, Dr Paula Durante Andrade and Bsc Rodrigo Lima (technician), also from FCM/UNICAMP. (AU)