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DEVELOPMENT OF A CELLULAR PROTOCOL TO SIMULATE THE LEAKY GUT SYNDROME AIMING AT OBTAINING THERAPIES AGAINST MULTIFACTORIAL DISEASES.

Grant number: 24/00884-0
Support Opportunities:Research Grants - Innovative Research in Small Business - PIPE
Start date: September 01, 2024
End date: May 31, 2025
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Cristiano Ruch Werneck Guimaraes
Grantee:Cristiano Ruch Werneck Guimaraes
Company:NINTX PESQUISA E DESENVOLVIMENTO LTDA
CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
City: São Paulo
Associated researchers:Ana Luíza Garcia Millás Massaguer ; Katia Sivieri ; Laira Lorraine Agostinho ; Mateus Kawata Salgaço ; Rita de Cássia Pessotti
Associated scholarship(s):24/15204-5 - Development of an in vitro protocol to simulate the permeability of the intestinal barrier (leaky gut) using a monolayer of Caco-2 cells., BP.TT

Abstract

Multifactorial diseases, such as metabolic diseases, cancer and inflammatory bowel diseases, are caused by genetic and environmental factors and interactions between them, sometimes mediated by the human microbiome. The change in the interspecies balance in the human intestine (dysbiosis) is linked to many pathologies, being more relevant in situations where the intestinal barrier is compromised, also known as the leaky gut syndrome. This allows for greater interaction between environmental triggers, gut microbiome and genetic susceptibility, leading to multifactorial diseases in the gut and other organs. The integrity of the intestinal barrier is maintained by a set of proteins located between epithelial cells (tight junction proteins), which forms a physical barrier and controls paracellular permeability. The change in the homeostasis of these proteins is what leads to the leaky gut. Several studies have shown that plant-based natural products, due to their evolutionary/ecological context, have great potential for restoring the leaky gut state, both directly and via modulation and metabolism by the intestinal microbiota. In this context, the present PIPE project proposes to evaluate the potential of natural products, more specifically of plant extracts, in restoring tight junctions dependently and independently of the intestinal microbiota. To this end, an in vitro protocol to simulate the leaky gut will be developed using monolayers of Caco-2 cells, which allows, through the induction of inflammation, evaluating the restoration of tight junctions after the administration of a treatment. Treatments will consist of (i) plant extracts and (ii) plant extracts fermented in our proprietary mini-xGIbiomics® technology with intestinal microbiota from individuals with inflammatory bowel diseases, with focus on ulcerative colitis as a model of a multifactorial disease. The absorption of this knowledge and the internalization of this in vitro protocol to simulate the leaky gut, as well as its use in conjunction with the proprietary technologies, GAIApath® and xGIbiomics®, from our biotech startup, called Nintx, will allow us to scale our business beyond the national territory with the development of therapies and new ingredients based on the Brazilian biodiversity, the provision of services and scientific collaborations. (AU)

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