Gut microbiota implicated in Alzheimer's disease
The gut microbiota of patients with Alzheimer’s disease has been found to be dysbiotic. But is it the cause of the disease, or a consequence? FMT experiments in rats suggest a causal role.
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Gut microbiota may be involved in Alzheimer’s disease. This is evidenced by specific alterations in gut flora in patients and in mouse models. But are these changes in gut microbiota the cause or a symptom of the disease? Research published in Brain 1 provides some answers.
Altered cognitive state and microbial signature
The 64 Alzheimer’s patients included in the study showed increased systemic inflammation compared with 69 healthy subjects. Their microbiota is enriched in Bacteroidetes (which includes many pro-inflammatory species) and depleted in Firmicutes and Verrucomicrobiota (known to be beneficial). Clostridium sensu stricto 1 and Coprococcus, producers of short-chain fatty acids, are less present, while the abundance of the pathobiont Desulfovibrio is increased.
These alterations in gut microbiota have been shown to be associated with the clinical state of patients with Alzheimer’s, and in particular with MMSE (Mini-Mental State Examination) cognitive and memory assessment scores: the less Coprococcus present, the lower the MMSE score; the more abundant Desulfovibrio and Dialister, the worse the MMSE score. These results point to a microbial signature of impaired cognitive performance in Alzheimer’s disease.
60-70% of cases Dementia results from various diseases and lesions that affect the brain. Alzheimer’s disease is the most common cause of dementia, accounting for 60-70% of cases.
Over 55 million Currently, over 55 million people worldwide suffer from dementia. Every year, there are almost 10 million new cases.
FMT modifies colonic function...
All that remained was to understand the contribution of human gut microbiota to Alzheimer’s disease. To do this, the team transplanted fecal samples from Alzheimer’s patients and healthy subjects into young adult rats with microbiota depleted by 7 days of antibiotics. While taxon diversity is maintained in rats that received healthy flora, FMT of microbiota from an Alzheimer’s patient induces a greater change in taxa, with a particular increase in Desulfovibrio. The colonic function of rats that received the microbiota of an Alzheimer’s patient was also modified (wetter stools, shortening of the colon, crypt hyperplasia of the proximal colon...).
...and transfers memory impairment
Above all, rats that received the microbiota of an Alzheimer’s patient performed less well on certain tasks, notably those involving long-term spatial memory and physiologically dependent on neurogenesis, the process by which neural stem cells in the hippocampus generate new neurons throughout life. Moreover, the authors show that FMT of microbiota from an Alzheimer’s patient affects this neurogenesis, and in particular the survival and dendritic arborization of neurons. How? Probably via the vascular route. The authors point at certain bacterial metabolites capable of crossing the blood-brain barrier. The authors also show that in vitro, bathing embryonic hippocampal progenitor cells in serum from Alzheimer’s patients affects neuronal proliferation, differentiation and dendrite morphology.
These results, which need to be confirmed by other studies (mechanistic, interventional, metabolomic, etc.), show that Alzheimer’s disease is not confined to the brain alone. They could inspire new approaches aimed at delaying the onset or slowing the progression of dementia, or even be applied to other neurodegenerative and cognitive disorders.
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