Ok, yeah…more on fecal microbiota transplants (FMT). This is my obsession for the week. But after reading my last post…can you blame me?!
In that post, in case you missed it, I talked about a new article reviewing the potential of FMT to treat a huge variety of illnesses, and included in that list was Alzheimer’s disease (AD). Imagine my joy, then, when I spotted a brand new bit of research looking more in depth at FMT’s effects on AD. Yes, this is a mouse model but still – it’s very promising.
This study[i], out of South Korea, used mice that have been genetically created to develop the same type of neurological issues (amyloid plaques, neurofibrillary tangles, and memory deficits) as those with AD. They refer to this group of mice as “ADLP mice.” As controls, they used healthy wild-type (WT) mice, with normal bacterial microbiomes. In comparing the two, they found that early in life (by 2 months), the microbiome of the ADLP mice begins to shift from the norm. The gut bacteria of ADLP mice did not so much differ from the WT mice in terms of specific types of bacteria, but rather, total composition of the flora, on a community-wide level. However, these differences, from a functional point of view, are extremely significant: “These gut-associated changes may mutually contribute to the increased gut barrier permeability and chronic inflammation seen in the intestine of ADLP mice; these problems are considered potential risk factors of AD.”
Which brings me to the next major difference between the two kinds of mice. ADLP mice display a “…loss of epithelial barrier integrity [leaky gut] and chronic intestinal and systemic inflammation.” By looking at the blood of the ADLP mice, they determined that indeed, metabolites (including highly toxic lipopolysaccharides (LPS)) produced by gut bacteria were making their way into the circulatory systems of the animals, causing a body-wide inflammatory response. High gut permeability “…can deteriorate the blood-brain barrier, and CNS [central nervous system] is easily exposed to the contents of the altered gut microbiota. LPS has been found in the brain and participates in AD pathology.”
The crux of the experiments: the scientists orally gave the ADLP mice fresh feces from the WT mice nearly daily for 16 weeks. Within 2 months, the gut bacteria of the mice was significantly altered, and after 4 months, the microbiota of the two groups of mice were indistinguishable. They then tested the mice’ memory, both long and short term, and found significant improvement in cognitive function. They also found that the amyloid plaques were “significantly decreased” as were the other neurological alterations in the ADLP mice.
Another interesting finding: the researchers discovered altered gene expression in in tissue from the colons of the ADLP mice, which was normalized by FMT. The genes that were altered “…are associated with ageing-related tissue degeneration and deterioration of mucosal immunity…Specifically, the genes unregulated in ADLP mice contribute to decreased cell proliferation, cellular senescence and cell growth arrest, which are well-characterized ageing-related phenotypes. The downregulation of genes related to mitochondrial and ribosomal activities in ADLP mice…are considered key features of ageing and neurodegenerative diseases.”
The authors state, “These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLP mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.”
In doing my usual snooping around, I found a 2nd article – also just published – looking at the effects of FMT on a different mouse model of AD. And guess what? “We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.”[ii]
So the question I asked myself, in reading, and rereading the paper – and writing this blog post – is: AD is currently an incurable terminal illness that brings heartbreak to the affected person and their families. (You can read about my own devastating personal experiences with it here.) Where are the clinical trials in humans?! And good news, for once, everyone: the University of Wisconsin is conducting one right now, as I type this. The study concludes in May 2022. If this blog still exists in 3 or so years, I’ll let you know the results!
[i] Kim, MS, et. al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut. 2019;0:1-12. doi: 10.1136/gutjnl-2018-317431.
[ii] Sun, J, et. al. Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgeneic mice. Nature. 2019;9(189).