Various cell types in the intestinal mucosa are constantly exposed to complex signals
emanating from the lumen, including the microbiota and its metabolites. How these bilateral
interactions in turn influences intestinal homeostasis is an important question in order to
understand microbiota-host interactions. This thesis has attempted to address this question in
the following papers. Deletion of the diet- and microbiota-regulated aryl hydrocarbon
receptor in CD11c+ cells was found to result in aberrant intestinal epithelium morphogenesis
and increased susceptibility of these mice to chemically induced colitis (Paper I). Our data
highlight a possible gateway of communication between the host and its environment,
through the AhR in intestinal antigen presenting cells, consequently regulating intestinal
epithelial cell biology and function.
In the second paper, we studied the impact of the microbiota on the development of the
enteric nervous system (ENS). The ENS controls many aspects of gut physiology, including
mucosal immunity. The major cellular component of the ENS is the enteric glia cell (EGC).
Our data showcased that the migration and expansion of EGC networks in the lamina propria
towards the lumen are under the influence of the microbiota. The postnatal expansion of
mucosal EGC networks was found to coincide with the same period where the microbiota
increases in number and diversity. Moreover, this microbiota-driven mechanism is an active
process that can be impaired following the exposure to antibiotics, which abrogate signalling
pathways mediating the host-microbe cross talk.
In the final manuscript, we developed a co-culture model system to study EGC functions
further, in relation to intestinal epithelial barrier functions. Using genetic labeling techniques
and live cell imaging, we observed close associations of EGCs with co-cultured intestinal
epithelial organoids ex vivo, reminiscent of the contacts reported between these two cell types
in vivo.
In conclusion, this thesis open more questions than answers especially as it addresses the
issue of cross communication between different biological systems required for the
development of complex organisms. The new player here is the microbiome and how it
constantly affects the response of different cell types, including cell-to-cell communications,
important for cellular adaptation to environmental cues. Future work will address the precise
molecular and cellular mechanisms underlying the interplay between the microbiota and hosttissues
to establish and maintain intestinal homeostasis
