Dacil Yanez Martin

The gastrointestinal tract is a complex biological system that transports complex fluids for subsequent digestion and absorption. Transport is induced by smooth muscle cells leading to macroscopic deformations of the tube, but at microscopic scales, the system presents villi, finger-like structures, and mucus, a hydrogel, whose role in transport phenomena is poorly understood. The objective of this thesis to understand how mechanical stimulation of the small intestine modulates motility and transport phenomena at both organ and villi scales.
Firstly, to investigate motility and transport phenomena, we needed a platform that offered a compromise between physiological relevance and experimental accessibility. For this reason, we developed an instrumented organ bath coupled with dedicated image analysis algorithms to assess motility at organ and villi scales under controlled mechanical boundary conditions. Once developed, we applied the framework to study the ex-vivo rat duodenum.
In the first part of the thesis, we aimed to characterized how the motility patterns could be modified under different mechanical boundary conditions. Our results show that, under isotonic conditions, segment length modulated both contraction frequency and amplitude, and that changes in amplitude were associated with changes in the size of contraction events.
In a second experiment we wanted to asses how this motility changes could influence particle adhesion on the intestinal mucus layer. The motility patterns were modified by applying intraluminal pressure. We were able to show that increasing intraluminal pressure led to a change on motility patterns that reduced particle adhesion on the mucosal surface. This suggested that motility patterns on the serosal surface could affect motility patterns at the villi scale.
In order to test this hypothesis, we performed a third experiment in which motility was characterised at both the villus and serosal scales simultaneously. We observed that serosal and mucosal dynamics remained largely synchronized, exhibiting only small, localized phase offsets. These findings support the idea that changes in serosal motility can propagate to the villus scale and modulate particle adhesion.
In summary, this thesis delivers a reproducible experimental and analytical framework for high-resolution mapping of intestinal kinematics and shows how the mechanical environment modulates nearsurface particle transport. These findings contribute to a better understanding of the complex interplay between mechanical stimuli, motility patterns, and transport phenomena in the small intestine, with potential implications for drug delivery and nutrient absorption.

Membres du Jury :

Clément DE LOUBENS     —   Directeur de thèse
CHARGE DE RECHERCHE HDR, CNRS Alpes
Nicolas CHEVALIER     —   Rapporteur
CHARGE DE RECHERCHE, CNRS Paris-Centre
Sahar EL AIDY     —   Rapporteure
FULL PROFESSOR, University of Amsterdam
Myriam GRUNDY     —   Examinatrice
CHARGEE DE RECHERCHE HDR, Institut National de Recherche pour la Agriculture, l'Alimentation et l'Environnement (INRAE)
Gladys MASSIERA     —   Examinatrice
PROFESSEURE DES UNIVERSITES, Université de Montpellier
Gregory CHAGNON     —   Examinateur
PROFESSEUR DES UNIVERSITES, Université Grenoble Alpes
Paul MENUT     —   Examinatrice
PROFESSEUR DES UNIVERSITES, Université Paris-Saclay

Invités :

Stéphane TANGUY    —  Co-encadrant de thèse
MAITRE DE CONFERENCES, Université Grenoble Alpes
Claude Loverdo
CHARGEE DE RECHERCHE HDR, Sorbonne Université