Abstract
Chronic wasting disease (CWD) is a fatal, contagious, neurodegenerative prion disease affecting both free-ranging and captive cervid species. CWD is spread via direct or indirect contact or oral ingestion of prions. In the gastrointestinal tract, prions enter the body through microfold cells (M-cells), and the abundance of these cells can be influenced by the gut microbiota. To explore potential links between the gut microbiota and CWD, we collected fecal samples from farmed and free-ranging white-tailed deer (Odocoileus virginianus) around the Midwest, USA. Farmed deer originated from farms that were depopulated due to CWD. Free-ranging deer were sampled during annual deer harvests. All farmed deer were tested for CWD via ELISA and IHC, and we used 16S rRNA gene sequencing to characterize the gut microbiota. We report significant differences in gut microbiota by provenance (Farm 1, Farm 2, Free-ranging), sex, and CWD status. CWD-positive deer from Farm 1 and 2 had increased abundances of Akkermansia, Lachnospireacea UCG-010, and RF39 taxa. Overall, differences by provenance and sex appear to be driven by diet, while differences by CWD status may be linked to CWD pathogenesis.
Highlights
Chronic wasting disease (CWD) is a fatal, contagious, neurodegenerative prion disease affecting both free-ranging and captive cervid species
CWD causes spongiform lesions within the central nervous system caused by an abnormal, diseased isoform ( PrPCWD) of the normal cellular prion protein (PrPC). PrPC is typically composed of multiple alpha-helices, but the abnormal isoform undergoes a transformation into a beta-sheet conformation, making it resistant to proteases, high temperatures, and standard disinfection protocols[1]
When we examined the gut microbiota of all deer (n = 229), we found significant differences in gut microbial composition and diversity by provenance (Farm 1, Farm 2, Free-ranging), with farmed deer having greater microbial diversity than free-ranging deer
Summary
Chronic wasting disease (CWD) is a fatal, contagious, neurodegenerative prion disease affecting both free-ranging and captive cervid species. To explore potential links between the gut microbiota and CWD, we collected fecal samples from farmed and free-ranging white-tailed deer (Odocoileus virginianus) around the Midwest, USA. Chronic wasting disease (CWD) is a fatal, contagious, neurodegenerative prion disease affecting both freeranging and captive cervid species, including white-tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), elk (Cervus elaphus elaphus), and moose (Alces alces). The gut microbiome has been linked to human neurologic conditions via the “gut-brain a xis21.” Both Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) have similarities to prion diseases and involve abnormal protein aggregates and protein misfolding occurring in the brain, including a conversion of alpha-helical structures to beta-sheet structures in PD22–26. Microbial colonization of germ-free mice with stool samples from patients with PD resulted in the disease-typical protein-misfolding-mediated motor d eficits[31]
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