The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease

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Hauptverfasser: Ismeurt-Walmsley, Caroline, Giannoni, Patrizia, Servant, Florence, Mekki, Linda-Nora, Baranger, Kevin, Rivera, Santiago, Marin, Philippe, Lelouvier, Benjamin, Claeysen, Sylvie
Format: Preprint
Veröffentlicht: 2024
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author Ismeurt-Walmsley, Caroline
Giannoni, Patrizia
Servant, Florence
Mekki, Linda-Nora
Baranger, Kevin
Rivera, Santiago
Marin, Philippe
Lelouvier, Benjamin
Claeysen, Sylvie
author_facet Ismeurt-Walmsley, Caroline
Giannoni, Patrizia
Servant, Florence
Mekki, Linda-Nora
Baranger, Kevin
Rivera, Santiago
Marin, Philippe
Lelouvier, Benjamin
Claeysen, Sylvie
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2412_18258
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease
Ismeurt-Walmsley, Caroline
Giannoni, Patrizia
Servant, Florence
Mekki, Linda-Nora
Baranger, Kevin
Rivera, Santiago
Marin, Philippe
Lelouvier, Benjamin
Claeysen, Sylvie
Neurons and Cognition
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.
title The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease
topic Neurons and Cognition
url https://arxiv.org/abs/2412.18258