Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in 5xFAD mice
The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigen, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. We found that M cell numbers were increased in the colons of five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota and ameliorated AD pathologies including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies in Spib-/- mice. Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.
2024 Spring Convention