Résumé
The gut-brain axis has emerged as a key player in the regulation of brain
function and cognitive health. Gut microbiota dysbiosis has been observed in
preclinical models of Alzheimer's disease and patients. Manipulating the
composition of the gut microbiota enhances or delays neuropathology and
cognitive deficits in mouse models. Accordingly, the health status of the
animal facility may strongly influence these outcomes. In the present study, we
longitudinally analysed the faecal microbiota composition and amyloid pathology
of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a
conventional facility. The composition of the microbiota of 5XFAD mice after
aging in conventional facility showed marked differences compared to WT
littermates that were not observed when the mice were bred in SOPF facility.
The development of amyloid pathology was also enhanced by conventional
housing. We then transplanted faecal microbiota (FMT) from both sources into
wild-type (WT) mice and measured memory performance, assessed in the novel
object recognition test, in transplanted animals. Mice transplanted with
microbiota from conventionally bred 5XFAD mice showed impaired memory
performance, whereas FMT from mice housed in SOPF facility did not induce
memory deficits in transplanted mice. Finally, 18 weeks of housing SOPF-born
animals in a conventional facility resulted in the reappearance of specific
microbiota compositions in 5XFAD vs WT mice. In conclusion, these results show
a strong impact of housing conditions on microbiota-associated phenotypes and
question the relevance of breeding preclinical models in specific pathogen-free
(SPF) facilities.