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

Abstract

The gut microbiome is emerging as an important susceptibility factor in Alzheimers 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 naive 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.

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome

“…While a causal link between dysbiosis and disease is difficult to demonstrate in humans, dysbiosis is often suspected to have a role in the initiation, manifestation, and progression of disease. In animal models, however, the use of germ-free mice and the manipulation of the microbiome with populations of bacteria or faeces from patients with neurodegenerative diseases have provided evidence of causation [32,211,212].…”

The gut microbiota is an emerging target for improving brain health during ageing

“…This coincided with alterations in microbial metabolites such as short-chain fatty acids (SCFAs; D’Amato et al, 2020 ) which have previously been shown to regulate host microglial maturation and function ( Erny et al, 2021 ). Moreover, using humanised models by transplanting FMT from older subjects with Alzheimer’s disease into microbiota-depleted naïve adult rats showed impairment in hippocampal neurogenesis accompanied with memory deficits, which correlated with clinical cognitive scores ( Grabrucker et al, 2022 ). Furthermore, young mice who received gut microbiota from aged donors suffered increased rates of mortality following ischemic stroke, along with increased levels of pro-inflammatory plasma cytokines and impaired motor strength ( Spychala et al, 2018 ).…”