Birth pathway and its influence on the gut microbiota: implications for health and response to environmental pollutants

• Grant number: 21/11319-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2023
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Juliana Elaine Perobelli
• Grantee: Marcella da Silva Araujo Santiago
• Host Institution: Instituto do Mar (IMar). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated scholarship(s): 23/13458-7 - Assessment of the impacts of dysbiosis caused by cesarean section on the gut microbiome's capacity to metabolize di(2-etilhexil) phthalate (DEHP)., BE.EP.DR

Abstract

The gastrointestinal tract hosts about 10(13) bacterias, viruses, fungi and protozoa that, living in community, form the gut microbiota. Dysbiosis is an imbalance in the composition of this microbiota, and it may occur due to several factors, being the birth pathway the main modulating factor in the neonate. In a state of dysbiosis, the many functions performed by the gut microbiota can be altered, such as the modulation of the immunological system, the physiology of many organs and the metabolism of xenobiotics, such as environmental pollutants. Therefore, the aim of this study is to investigate if the state of dysbiosis in the gut microbiota, induced by cesarean section, is persistent along the individual's life, causing persistent implications for the animal's general health and the body's response to environmental pollutants such as the phthalate DEHP. In order to do that, male Wistar rats born via vaginal delivery (VD) or cesarean section (CS) will be used for: (i) evaluation of the gut microbiota composition by large-scale DNA sequencing, in colon samples, throughout postnatal life (PND 1, 21 and 90); (ii) evaluation of the immunomodulatory profile throughout postnatal life, through analysis of the permeability of the intestinal epithelial barrier, and immunomodulatory in colon, thymus, testis and epididymis (PND 21 and 90); (iii) evaluation of histomorphometric and physiological parameters in colon, testis and epididymis (PND 21 and 90). Still, in order to investigate if the cesarean section modulates the pattern of toxicity of environmental pollutants, after weaning, part of the remaining animals will receive oral treatment with DEHP for 65 days (PND 25 to 90). In these animals, reproductive parameters will be evaluated, since DEHP is known for altering the physiology of the reproductive system. The proposed study will allow advances in questions of translational relevance regarding the impacts of the birth pathway on the composition and functionalities of the gut microbiota of individuals in the long term, opening possibilities for studies in order to mitigate such impacts. In addition, the study with DEHP will allow advancing knowledge about the role of the birth pathway in modulating the individual's response to a toxicological challenge, also allowing the prospect of mitigating strategies from the modulation of the gut microbiota.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTIAGO, MARCELLA S. A.; AVELLAR, MARIA CHRISTINA W.; PEROBELLI, JULIANA E.. Could the gut microbiota be capable of making individuals more or less susceptible to environmental toxicants?. Toxicology, v. 503, p. 47-pg., 2024-02-23. (21/08127-6, 21/11319-4)