Home Alzheimer's and Dementia Gut bacteria play key role in Alzheimer’s and dementia

Gut bacteria play key role in Alzheimer’s and dementia

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An increased risk of Alzheimer’s and dementia is linked to the make-up of the gut microbiome and damage to the brain can be prevented or accelerated by changes to the balance of the gut bacteria, according to four separate studies.

Previous studies have shown that people who develop Alzheimer’s and Dementia have a lowered microbiome both in total volume of bacteria and in diversity of types. But is this just an association, or is it causal?

A team from King’s College, London and University College, Cork decided to study whether the poor microbiome of someone with Alzheimer’s could induce Alzheimer’s in another animal. And the answer was clearly that it could (1).  A poor microbiome can be causal in Alzheimer’s and Dementia

Having used antibiotics to clear any bacteria from the hosts (rats), transplanted microbiomes from Alzheimer’s patients into these rats led to impaired behaviors due to a restriction in a process called ‘adult hippocampal neurogenesis’. It’s a process essential for some aspects of memory and mood because a heathy animal can generate and grow new nerve cells in the brain.  The poor microbiomes in Alzheimer’s patients restricted this; they stopped the growth of new brain nerve cells.

In the Alzheimer’s patients, the microbiomes also contained more bacteria that generated inflammatory compounds, and the degree of the damage in the rats receiving the microbiome transplants was totally linked to the severity of the original patient’s Alzheimer’s.

Previous microbiome studies on Alzheimer’s

Amyloid plaques are sticky proteins that build up in the brains of Alzheimer’s patients. This build up prompts an immune response, which causes chronic inflammation and in turn this damages the nervous tissue.

Researchers, Andreas Bäumler and his team at UC Davis School of Medicine showed that if they injected mice with E. coli and Salmonella bacteria, curli fibril proteins (CsgA) produced by the bacteria stuck to other curli fibres and to the gut wall, forming colonies resembling plaques. This caused an immune response.

These aggregates of curli fibrils are similar in structure to the amyloid fibrils in the brain plaques. Bäumler hypothesized that what was happening was a case of ‘mistaken identity’ by the immune system, which attacked the colonies in the gut and thus the plaque in the brain.

The research team then showed (2) that when they destroyed the ability of the proteins in the gut to aggregate, the inflammation in the brain and the immune reaction stopped in the brain.

“The CsgA peptide in the gut and beta-amyloid don’t have anything genetically in common. The similarity is only in the structure of the amyloids they form. Our study indicates that there is some structural feature of amyloids that triggers the innate immune system,” Bäumler said.

Chris Woollams, former Oxford University Biochemist added, “Studies like this are crucial to understanding the process in Alzheimer’s. Hitherto, drug companies have been unsuccessful because they were just shooting in the dark. And because they thought the answer to Alzheimer’s, Dementia and even Parkinson’s lay in the brain. It doesn’t. We’ve known for a long time now that there’s a gut-brain axis and that the brain microbiome reflects the gut microbiome; good or bad. More work on the gut may well show that the solution to Alzheimer’s lies in healing your gut, rather than tackling issues occurring in the brain”.

How right this observation is. In 2017, a further study (3) was produced by researchers at Lund University in Sweden. Here they compared the gut microbiome of mice with Alzheimer’s, mice without the disease, and with mice with no gut bacteria at all. This last group had virtually no amyloid plaque build up in the brain. When they took the bacteria from the diseased mice they immediately saw plaque build up; but when using bacteria from transplanted from healthy mice, there was only a little. Almost the same conclusion as the first study, above.

Clearly then, the answer lies in the gut microbiome and infection. Researchers now hope to find out the make-up of the gut in mice with brain disease and study in what ways they could control the development.

The final study (4), this time from Researchers at the University of Wisconsin, showed that humans with Alzheimer’s had decreased overall levels of gut bacteria plus a reduced diversity. In particular, patients developing Alzheimer’s disease had lowered levels of the species Firmicutes. They too hypothesised that the way to prevent and treat Alzheimer’s and dementia actually lay in the gut, not the brain.

Could you reverse Dementia and Alzheimer’s?

Chris Woollams, former Oxford University Biochemist, adds, “The real question after these findings is ‘Could you reverse Dementia and Alzheimer’s?’ The answer seems potentially to be ‘Yes you could’, but, most likely, only at early stages before the problems in the gut have caused actual damage to the brain tissues.

By correcting the microbiome, we already know that you can change inflammatory issues in the brain astrocytes, from work on brain cancer. And we know that neuroinflammation is to blame in Alzheimer’s. Decline in the diversity of the gut microbiome can lead to an increase in the permeability of the gut wall and immune cell activation, and this leads to damage in the blood–brain barrier function promoting neuroinflammation and nerve cell loss (5). MIT researchers have found that an enzyme CDK5, is overactive in the brains of people with Alzheimer’s as a result and a peptide (a small piece of protein), can block it (6).

On one of my Sunday Shows, my guest was Dr. Julian Kenyon, who is retired but used to run the Dove Clinic. He had produced a major research study on how supplementing a damaged microbiome with trillions of the two families, Lactobacillus and Bifidobacterium, and with high dose butyrate, a short chain fatty acid produced by gut bacteria in a healthy microbiome and known to heal the gut wall, reduce inflammation and even cross the blood brain barrier, could reverse early stage Dementia and Alzheimer’s. This replenishment step is identical to one of the steps in our ‘Heal Your Gut’ protocol”.

Find out more about the role of your gut in chronic illness, and particularly how to heal your gut, here ….

Go to: Heal your gut now!’

Go to: Exercise can reduce risk of Alzheimer’s and Dementia

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 References

  1. Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis. Grabrucker S, Marizzoni M, Silajdžić E, et al. Brain. 2023:awad303.
  2. Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents; Sergei Perov et al; PLoS Pathog; 2019 Aug 30;15(8):e1007978
  3. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota; T. Harach, N. Marungruang, N. Duthilleul, V. Cheatham, K. D. Mc Coy, G. Frisoni, J. J. Neher, F. Fåk, M. Jucker, T. Lasser, T. Bolmont. Scientific Reports, 2017; 7: 41802 DOI
  4. Gut Microbiome alterations in Alzheimer’s disease; Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE; Scientific Reports: 19 October 2017. doi:10.1038/s41598-017-13601-y
  5. The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?; Ashwinipriyadarshini Megur et al; Nutrients. 2021 Jan; 13(1): 37.
  6. A new peptide may hold potential as an Alzheimer’s treatment; Anne Trafton; MIT News Office Publication Date April 13 2023,