Multi-Omic Analysis of Metabolism and Microbiome in Healthy Dogs and Cats and Those with Oral Melanoma

• Grant number: 23/16785-9
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): February 01, 2024
• Effective date (End): January 31, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Thiago Henrique Annibale Vendramini
• Grantee: Natacha Teixeira
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/06499-6 - Multi-omic analysis of metabolism and microbiota of healthy and sick dogs and cats, AP.GR

Abstract

Neoplastic diseases are typically associated with severe weight loss. This weight loss is referred to as "cancer cachexia" (MICHEL et al., 2004), which can occur either due to a physical obstruction hindering the proper passage of food through the gastrointestinal tract or as a result of paraneoplastic syndrome, which requires further studies for a complete understanding of its development (FASCETTI & DELANEY, 2012). In the case of paraneoplastic syndrome, the animal usually experiences inefficient use of nutrients that provide energy (proteins, fats, and carbohydrates), making it a challenge to meet its nutritional needs. It is believed that the alteration of inflammatory mediators and various metabolites resulting from the neoplastic process is responsible for the increased energy demand and, thus, the primary reason for weight loss (MICHEL et al., 2004). Factors beyond tumor genomics influence cancer development and therapeutic responses, including host-related aspects such as metabolic responses, body condition and composition, and intestinal/fecal microbiome. However, more studies are needed to precisely understand how these alterations occur. Oral tumors encompass neoplasms arising from the gums, oral mucosa, lip mucosa, palate, tongue, tonsils, or dental elements (FOSSUM, 2015; REQUICHA et al., 2015) and are commonly reported in the clinical care of dogs and cats (SALGADO et al., 2008; FOSSUM, 2015; MIKIEWICZ et al., 2019). They are mostly benign (VERHAERT, 2010; WINGO, 2018). Malignant tumors represent approximately 5.4 to 7% of all tumors in dogs and have a reserved prognosis, primarily due to late diagnosis in many cases (VERHAERT, 2010; PROUTEAU & ANDRÉ, 2019). The investigation of how environmental factors influence oncogenesis and tumor progression, as well as how manipulations of the intestinal microbiota can improve the clinical performance of antitumor therapeutic agents, is a recent approach in human medicine (ZITVOGEL et al., 2015). The microbiota is known to have constant communication with various reactions occurring in the host's body, and this communication undergoes changes over time. The microbiota-host interaction resembles hormonal reactions, such that, in response to certain physiological changes, microbial modifications occur (HOLMES et al., 2012; NICHOLSON et al., 2012). As the role of the microbiota in host health is studied more, opportunities arise to explore this interaction to improve therapeutic responses to various diseases, including cancer. Metabolomics aims to analyze various metabolites in a plasma sample, and lipidomics focuses on the comprehensive study of lipids present in a specific organism, emphasizing lipid metabolism and its relationship to disease progression. This approach aims to understand the possible metabolic adaptations of an organism in the face of a particular disease. The information obtained allows for a better understanding of the disease stage, oxidative stress caused by it, and, consequently, the data obtained usually provide better support for a more effective therapeutic approach (WECKWERTH & MORGENTHAL, 2005; BANDO et al., 2010, KAWABE et al., 2015). The metabolic profile of animals affected by oral neoplasms likely differs from that of healthy animals, as does the fecal microbiota, and further studies are needed to understand this reciprocity between fecal microbiota, genetic and metabolic variations through "omics" sciences (lipidomics and metabolomics), and the body composition of dogs and cats affected by this type of neoplasia.