Effects of tributyrin supplementation on the gut microbiota of patients with Cancer cachexia

• Grant number: 21/14015-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2022
• Effective date (End): March 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Flaydson Clayton Silva Pinto
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cachexia is a metabolic disorder characterized by rapid weight loss (muscle and adipose tissue), which affects up to 80% of patients with advanced Cancer, and is related to functional decline and survival. Pro-inflammatory cytokines, such as TNF-± and IL-6, directly contribute to the progression of this condition. The regulation of inflammation, through activation of Toll-like receptors 4 (TLR4) by bacterial lipopolysaccharide (LPS), as well as changes in the microbiota and its metabolism in cachexia, as observed in preliminary experiments of the group, may be all relevant factors in the development and/or progression of the wasting disease. We hypothesize that supplementation of butyrate (in the form of tributyrin), a metabolite that regulates the biology of intestinal microorganisms, may mitigate the symptoms of cachexia in Gastrointestinal Cancer. Therefore, this study aims to characterize the fecal microbiota, (shotgun sequencing), in patients with stable weight or cachectic Gastrointestinal Cancer, after supplementation or not with tributyrin. In addition, plasma biochemical and inflammatory parameters, tumor and healthy stomach or intestine tissue histology, as well as cytokine production in these organs will be investigated. Additionally, an immunofluorescence study will be performed to quantify the nuclear protein Ki-67 in the tumor, and also the expression of CD31, CD45, CD14, CD56, CD3, CD11b, to investigate the characteristics of the tumor microenvironment. Finally, we will analyze the gene expression of interleukins IL-1², -6, -8, -10 and TNF-± in the tumor. (AU)