More Evidence that Microbiome Alterations (With a Little Genetic Help) are a Factor in Alzheimer’s

Researchers at the University of Oregon just published a paper in Scientific Reports that shows an incredible correlation between the gut bacteria and neurodegenerative diseases, including Alzheimer’s.[i]  The study was done on mice that had been genetically engineered to carry genes (apolipoprotein E and Tomm40) associated with the development of Alzheimer’s.  (Until I read this, I didn’t actually realize there was a known genetic component to at least some cases of Alzheimer’s disease.)

These mice, and wild-type controls, were fed the same diet and yet those with the genetic mutation ended up with a different microbiome composition, and then these genetically-prone mice displayed cognitive and behavioral changes consistent with the development of the disease.  There was a direct correlation between the microbiome and epigenetic changes  in the neurons of the hippocampus, which is the part of the brain affected in Alzheimer’s – one of the main “memory” areas of the brain:  “The results of this study indicate that the taxonomic diversity and composition of the microbiome correlate with both behavioral/cognitive performance and levels of DNA methylation at certain disease-relevant genes…”

At this point they still don’t know for sure which is the chicken or the egg:  that is, did the changed microbes cause the behavioral changes through epigenetic changes or…did epigenetic alterations cause changes to the microbiome:  “However, our associative study is unable to discern cause and effect relationships between connected components, nor does it reveal the functional pathways through which gut microbiota link to the brain epigenome or behavior…”  However,  their continued research should help clarify this and they will be looking at whether or not it’s possible to reduce Alzheimer’s symptoms in mice by altering their diets.  The lead researchers states, “The exciting part of this is that you can manipulate the gut microbiome…We can use probiotics and see what the effect is.”[ii]  At least now they have identified suspicious species that are involved and that may “…serve as strong candidates for future studies…”  So definitely progress.

I was amazed to learn that a recent observational study in humans with Alzheimer’s showed similar findings: those with these genes showed microbiome alterations and subsequent epigenetic changes.  I noticed, by the way, that there is a clinical trial (currently recruiting) being conducted by researchers from a hospital in Shanghai, in collaboration with Massachusetts’s General Hospital (one of Harvard’s teaching hospitals), which will assess whether or not the gut bacteria of AD patients is different from that of their spouses or other controls.

In the meantime, the evidence that microbiome alterations are a major player in the development of Alzheimer’s continues to mount.  From the concluding paragraph of this paper:  “These data suggest that as seen in Parkinson’s disease (PD) and PD models7, the gut microbiome might be a contributor to AD in humans…”

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[i] Payel Kundu et al, Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice, Scientific Reports (2021). DOI: 10.1038/s41598-021-83851-4

[ii] https://medicalxpress.com/news/2021-02-gut-microbiome-alzheimer-like-behavior.html