Microbiota and Alzheimer’s disease

By Pr. Pascal Derkinderen
Neurology department, Nantes University and Inserm U1235, Nantes, France

About this article

Created 01 February 2024

Updated 22 October 2024

Commentary on the article of Ferreiro et al. Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease. Sci Transl Med 2023; 15:eabo2984.

The intestine-brain microbiota axis is a “trending“ subject in the field of neurodegenerative diseases and Alzheimer’s disease (AD), the most frequent of them all, is no exception. A recent meta-analysis identified 17 studies of this type (438 individuals with AD and 672 controls) [1]. Although the results of these studies can sometimes differ, the general consensus is that the dysbiosis observed in cases of AD is the result of a change to a ”proinflammatory” profile [1]. All available studies concern symptomatic AD with cognitive impairment, and there are so far no data concerning preclinical AD. This phase of the disease precedes the cognitive disorders by several years and during this time the new biological markers and imaging can detect the amyloid pathology, one of the two neuropathological characteristics of the disease. This lack is now addressed with this recent publication in which the authors have used to good advantage a somewhat original cohort, that is 164 individuals subjected to a longitudinal follow up of their cognitive functions, coupled with brain imaging (positron emission tomography - PET - and lumbar puncture), these latter two examinations detecting directly or indirectly the presence of b-amyloid peptide deposits [2]. At the time of the analysis of the gut microbiota (between 2019 and 2021), the subjects were aged 68 to 94 years (45% men); at this date, out of the 164 subjects, 49 were classified as having a preclinical form of AD, i.e. they were positive for amyloid markers in the imaging and/or in the cerebrospinal fluid in the absence of clinical cognitive impairment. The analysis of the microbiota showed differences between healthy subjects and those with preclinical AD: the species most significantly associated with preclinical AD were Dorea formicigenerans, Faecalibacterium prausnitzii, Coprococcus catus and Anaerostipes hadrus. The metabolic pathways associated with the preclinical forms of AD were those involved in arginine and ornithine degradation whereas the glutamate degradation pathway was most strongly associated with healthy subjects.

Do you think that analyses of stool samples may be soon added to tests designed to identify individuals with early Alzheimer’s disease in order to orientate them to appropriate treatments more rapidly?

After reading this article the first question which logically comes to mind is to ask oneself if the analysis of the microbiota could be proposed to identify those individuals with early stage or preclinical AD. From a neurologist’s point of view, the response is rather negative. This is because current data, both for symptomatic AD and for preclinical AD, have failed to identify a specific “standard” microbiota, which may distinguish these cases from a control population using routine stool analysis. Moreover, there are now markers of AD, reliable even at a preclinical stage, easily utilisable in a clinical context. Leaving aside PET imaging which is not available in all centres and analysis of the cerebrospinal fluid which involves a lumbar puncture which can be considered invasive, it is now possible to detect modifications in the expression and/or phosphorylation of certain proteins implicated in the neurodegenerative process in the plasma, i.e. in a simple blood sample, for cases of symptomatic AD as well as at the preclinical stage [3].

Would you consider sharing this publication with your patients to explain the relationship between the gut microbiota and the brain, in order to reinforce the key role played by the gut microbiota in human health?

To end on a more positive note, there is, however, no doubt that this article, by showing for the first time a modification to the composition of the microbiota in preclinical AD, provides new evidence that the microbiota may be involved in the development of AD, and moreover, at an early stage. In this context, its summary and a simplified version may be proposed to the general public or to some patients to emphasise the important role of the microbiota in health. Nevertheless, independent confirmation of these results by other teams will be necessary in the future.