Oral Administrations of Short-Chain Fatty Acids or Probiotics Extend the Survival Times and Mitigate the Neuropathological Damages in the Scrapie-Infected Hamsters.

Prion diseases (PrDs) are fatal neurodegenerative conditions marked by brain spongiform degeneration, prion protein scrapie (PrPSc) accumulation, neuronal loss, and gliosis. Currently, there are no effective treatments or preventive measures for these disorders. This study evaluated the therapeutic potential of short-chain fatty acids (SCFAs) and probiotics on PrDs using hamsters intracerebrally inoculated with the 263K scrapie strain. Treatments included oral administration of SCFAs (sodium propionate, butyrate, acetate) and probiotics (Clostridium butyricum, Bifidobacterium infantis). Clinical symptoms were monitored, and samples from brains, feces, and sera were collected at various time points for analysis. Assessments covered PrPSc deposits, gliosis, neuroinflammation, SCFA-related elements, gut microbiota profiles via 16S rRNA sequencing, and fatty acid levels measured by LC-MS/MS. Although all infected animals eventually died, those treated with SCFAs and probiotics showed a significant delay in clinical symptom onset and extended disease course. There was a notable reduction in the progression of PrPSc deposits, gliosis, and neuroinflammation in treated groups. Additionally, the decrease in SCFA receptors GPR41 and MCT4, along with downstream proteins Nrf2 and HO-1 in the brain, was slowed. Gut microbiota analysis revealed more beneficial bacteria in the SCFA and probiotic groups compared to controls. However, no significant differences were observed in serum and fecal fatty acid levels among groups. Oral administration of SCFAs and probiotics post-prion infection can effectively delay disease onset and progression while mitigating neuropathological changes associated with prion diseases. These results suggest a promising, cost-effective dietary intervention strategy for managing PrDs clinically.