Ascorbic acid as a strategy to improve inflammation and gut barrier disruption in a Caco-2 model: the role of butyric acid

• Grant number: 22/01269-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 16, 2022
• End date: July 24, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Debora Estadella
• Grantee: Breno Picin Casagrande
• Supervisor: Philip Charles Calder
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Institution abroad: University of Southampton, England
• Associated to the scholarship: 19/22511-3 - Strategy to minimize the adverse effects of replacing an obese diet with a standard diet on behavioral and neuroendocrine parameters in an animal model, BP.DR

Abstract

Obesogenic diets (ODs) induce adiposity increase and obesity-like features, such as inflammation, in humans and animal models. OD causes inflammation increase and barrier dysfunction in the small intestine. Toll-like receptor 4 (TLR4) inflammatory cascade is the main pathway associated with these changes. OD leads to dysbiosis which is followed by the increase in lipopolysaccharides (LPS) in the gut lumen also promoting the activation of the TLR4 pathway with a consequent rise in inflammatory markers and barrier disruption. Caco-2 cells are used to study such respects and the interaction between diet and gut. Ascorbic acid (AA) is a well-known antioxidant and has anti-inflammatory effects. Poor AA status is associated with poor health outcomes. AA supplementation can be a treatment for inflammatory gut diseases. However, excessive fat intake lowers AA via gut inflammation and barrier dysfunction. In Caco-2 models, TNF-± and LPS decreased AA absorption by hampering its receptor's function. Conversely, AA increases butyric acid (BA) production by microbiota, which can improve gut health. BA decreases inflammation and improves intestinal barrier integrity. We hypothesize that due to its anti-inflammatory role, lowering NFºB, BA could facilitate the AA effect by mitigating the LPS effect on its receptor. Hence, we propose treatment with AA, BA, or both on an LPS-stimulated Caco-2 cell model to evaluate inflammation, barrier integrity, and AA receptors. By using this model, we attempt to identify the molecular mechanisms in these relations, shedding light on new mechanisms, and helping to fill the gap in the current knowledge. (AU)