Microfluidic intestine-on-a-chip as a model for nutrient absorption

Author(s)

Jéssica Freire Feitor

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT)
• Defense date: 2022-10-06

Examining board members

Daniel Rodrigues Cardoso; Francisco Eduardo Gontijo Guimarães; Adriane Elisabete Antunes de Moraes; Ana Rita de Araujo Nogueira; Álvaro José dos Santos Neto

• Advisor: Daniel Rodrigues Cardoso

Abstract

Bioavailability and absorption of calcium are increasingly becoming a trending topic of study due to its correlation with a series of diseases such as osteosarcopenia. Those diseases are mostly related to the elderly population and are showing increasing numbers, affecting over 100 million people worldwide. Calcium malabsorption is the main cause of the low levels of this mineral into the body, and is related to the low solubility of calcium in most food types under neutral and alkaline conditions. Aside from physiological age-related problems, the poor solubility of calcium in food and the lack of calcium transporters may worsen its absorption into the intestine. The knowledge of the absorption of calcium ions by combining them with milk-derived peptides and hydroxy carboxylates is of nutritional relevance. The in vitro study of nutrients absorption is traditionally carried out by using pharmaceutic-derived approaches, such as the transwell® assay with the Caco-2 cells as a model for intestinal absorption. Although largely accepted, this model was proved obsolete and inconsistent if compared to the human system. The past few decades were marked by the advent of Organs-on-a-chip (OoaCs), which are now object of intense investigation for the most different approaches. Today, OoaCs are becoming an attractive substitute for the traditional methods of drug and nutrient uptake evaluation due to their dynamic character. Therefore, this work displays the study of calcium and peptide absorption by the use of two methods, the traditional static model (transwell®), and the dynamic two developed devices of intestine-on-a-chip (IoaC). By using the ESI-MS technique, the transwell® indicates an improvement of calcium absorption by the simple addition of CaCl2 to Peptigen® commercial whey hydrolysate. The IoaC, otherwise, indicates no significant change in calcium absorption. Moreover, this work gives insights on the development of possible calcium ion carriers and the permeability of important peptides through a peptidome analysis of Peptigen® using MALDI-TOF-MS/MS. Finally, the IoaC platforms show the permeation of fast absorption peptides in high levels, in contrast with a large number of peptides found in lower levels for the transwell® platform, indicating different mechanisms for those platforms. (AU)

• FAPESP's process: 18/11657-4 - Development of a multiplex FTIR microfluidic device for in vitro tests on bio-availability of calcium
• Grantee: Jéssica Freire Feitor
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)