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Table of contents
Introduction
The gastrointestinal tract
The digestive system, vital functions for the host
Components of the digestive system
Structuration of the gut wall
Gut microbiota
Intestinal epithelium
Enterocytes, Transport and cell junctions
Goblet cells and Mucus
Paneth cells
Tuft cells
Enteroendocrine cells
Intestinal stem cells
Cell differentiation
Enteroendocrine cells differentiation
Enteroendocrine cells
Role of enteroendocrine cells
Gastric hormones
Enzymatic secretion regulation
Gut motility regulation
Incretin hormone
Food intake control
Production and secretion of hormones
Regulation of hormonal production
Regulation of secretion in enteroendocrine cells
L-cells
Peptide YY
The NPY family and their receptors
NPY receptors
PP, NPY and PYY
Functions of PYY
Regulation of food intake by PYY
Intestinal motility, nutrient absorption
Metabolism
Bacterial products implicated in cross talk with EEC
Functional metagenomics to search for new bacterial genes regulating PYY expression and secretion
Short chain fatty acids
SCFAs production in the colon
Bacteria implicated in SCFAs produciton
SCFAs transport
SCFAs, Inhibitors of HDAC
SCFAs Receptors.
Effect of fiber rich diets and SCFA administration on PYY plasma levels
Regulation of secretion by SCFAs
MAMPs and TLRs
Role and structure of TLRs in the recognition of MAMPs
TLRs in epithelial cells and enteroendocrine cells
Model Development
Development of a reporter system for Pyy gene expression
Classical reporter systems
DNA repair to induce mutations or integrate a specific sequence
DNA double strand break
Strategy for a fluorescent reporter gene integrated in Pyy coding gene
Development of reporter systems for secretion
Calcium sensors
Live imaging for calcium imaging
Image analysis
Material and methods:
Cell coating, cell sorting and transfection
Plasmid construction
Results
Short Chain Fatty Acids differently regulate Peptide YY expression and secretion in human
enteroendocrine L-cells
Microbial sensing by TLRs in L-cells is increased by butyrate and modulates Pyy expression
Discussion
In vitro cellular models to study PYY release by L-cells
Modulation of PYY plasma levels
Importance of gene expression regulation
Differences between human and rodent Pyy encoding gene
PYY secretion in humans and rodents
Human cell lines modeling L-cells
Limitation of cell lines
Organoids, a future in in vitro studies?
Importance of microbial sensing by L-cells
Sensing of microbial products
Regulation of PYY expression by SCFAs
Mechanisms implicated in the response to SCFAs in the modulation of gene expression
Regulation of Pyy by microbial products through activation of receptors
Concentration of SCFAs sensed by L-cells
Regulation of PYY production by SCFAs
Regulation of secretion by SCFAs
SCFAs modulate sensing in L-cells
SCFAs and metabolism in L-cells
Beneficial effects of regulation of PYY production and secretion
PYY in germ-free animals
Genetics of PYY and obesity
Effect of SCFAs to modulate secretion for its anorexigenic effects
Obesity, microbiota, SCFAs and TLRs
Microbiota and PYY interrelations
Bibliography
