Faecal microbiota transplantation from Alzheimer’s participants induces impairments in hippocampal neurogenesis and cognitive behaviours in rats

Abstract The gut microbiome is emerging as an important susceptibility factor in Alzheimer’s disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naïve adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD.