Is there a Connection between Alzheimer’s Disease and the Intestine?


Alzheimer’s disease remains one of the leading causes of death in the United States. One in three seniors dies from Alzheimer’s or dementia – more than from breast and prostate cancer combined.

Proteins produced by Gut Bacteria May Trigger Alzheimer’s Disease

While a cure remains elusive, the link between brain health and gut microbiota is becoming increasingly clear. Research suggests that the bacteria in your gut can affect brain function and even promote neurodegeneration.

A team of researchers from Switzerland and Italy has taken this connection even further, demonstrating a link between an imbalanced gut microbiota and the development of amyloid plaques in the brain; Alzheimer’s disease is characterized by an accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain.

The study included a cohort of 89 people between the ages of 65 and 85. Some of them had Alzheimer’s disease or other neurodegenerative disorders, while others were healthy and had no memory problems.

The researchers used PET imaging to measure amyloid deposits in their brains, and then measured inflammatory markers and proteins produced by gut bacteria, such as lipopolysaccharides and short-chain fatty acids, in their blood.

Lipopolysaccharides (LPS) are dead bacteria or, more precisely, the cell walls of dead bacteria. Your immune system treats them as live bacteria and initiates an immune response against the supposed invaders. LPS are pro-inflammatory and have been found in amyloid plaques in the brains of Alzheimer’s patients.

The study found that high blood levels of LPS and the short-chain fatty acids (SCFAs) acetate and valerate were associated with large amyloid deposits in the brain. Other short-chain fatty acids, namely butyrate, appeared to have a protective effect; high levels of butyrate were associated with less amyloid.

Butyrate – an SCFA produced by gut bacteria during the fermentation of dietary fiber – activates the secretion of brain-derived neurotrophic factor (BDNF), reduced levels of which have been linked to Alzheimer’s disease.

“Our results are indisputable: certain bacterial products of the gut microbiota correlate with the amount of amyloid plaques in the brain,” explains Moira Marizzoni, a study author from the Fatebenefratelli Center in Brescia, Italy.

Probiotic ‘Cocktail’ may act as early Prevention Agent

The study represents a continuation of earlier research by the team, which found that the gut microbiota of people with Alzheimer’s differs from those without the disease. In people with Alzheimer’s, microbial diversity is reduced, with certain bacteria overrepresented and other microbes reduced.

“In addition,” said neurologist Giovanni Frisoni, study author and director of the Memory Center at the University Hospitals of Geneva (HUG) in Switzerland, “we also discovered a link between an inflammatory phenomenon detected in the blood, certain intestinal bacteria and Alzheimer’s disease; hence the hypothesis we wanted to test here. Could inflammation in the blood be a mediator between the microbiota and the brain?

As the link grows stronger, the team plans further research to determine which specific bacteria or groups of bacteria may be responsible for the effect, which could ultimately lead to a preventive treatment cocktail. Frisoni said in a news release:

Indeed, we first need to identify the strains of the cocktail. Then, a neuroprotective effect could be effective only at a very early stage of the disease, with an eye toward prevention rather than therapy.

However, early diagnosis remains one of the biggest challenges in treating neurodegenerative diseases, as protocols need to be developed to identify high-risk individuals and treat them long before recognizable symptoms appear.

The link to Fasting

One reason fasting is so beneficial in neurodegenerative diseases like Alzheimer’s is that it helps the body go through autophagy and the rebuilding phase.

Autophagy is the process by which the body eliminates damaged organelles and promotes the proliferation of new, healthy cells. This is related to Alzheimer’s because the process of refolding is one of several factors that must function in order for the brain to function.

Importantly, fasting activates autophagy, the body’s way of disposing of waste, and also triggers stem cell regeneration. In our 2017 interview, Dr. Steven Gundry explained that this may also be directly related to LPS and that ridding the gut of these proinflammatory proteins through fasting can be healing:

We have an amazing repair system that goes to work when we fast. If nothing else, it rests the gut. It’s probably one of the smartest things any of us can do – to let the gut wall rest, not have to absorb nutrients, not have to deal with the constant influx of lectins or toxins. But I think more importantly, it gives [the body] a chance to finally do some serious brain cleansing.

Alzheimer’s and Parkinson’s have a common cause, which is the brain defending itself against a perceived threat, many of which are LPS. If you quiet your gut and don’t allow LPS to enter your system, and the longer you can maintain that, the better off you will realistically be.

As Jason Fung would say, intermittent fasting is great; a modified reduced calorie diet is great, but it’s technically so much easier to just stop eating … The second level of my modified food pyramid is ‘eat nothing’.

Probiotics show promise in Alzheimer’s Disease

The effect of beneficial bacteria on brain health is well established, including in people with Alzheimer’s disease. A 2016 study of 60 Alzheimer’s patients examined the effect of probiotic supplements on cognitive function, with promising results. Those who drank milk containing probiotics experienced significant improvements in their cognitive functions.

While the average Mini-Mental State Examination (MMSE) score increased in the probiotic group, it decreased in the control group that drank normal milk.

The probiotic group also showed positive metabolic changes, including lower triglycerides, very low-density lipoprotein and C-reactive protein, a measure of inflammation, as well as lower markers of insulin resistance.

The researchers suggest that the positive metabolic changes may be responsible for the cognitive improvements. Walter Lukiw, a professor at Louisiana State University who was not involved in the study, told Medical News Today that the gut and brain are closely linked:

This is consistent with some of our recent studies that suggest that the GI [gastrointestinal tract] microbiome is significantly altered in composition in Alzheimer’s compared with age-matched controls….

…and that both the gastrointestinal tract and the blood-brain barrier become significantly less tight with age, allowing microbial exudates from the gastrointestinal tract (e.g., amyloids, lipopolysaccharides, endotoxins, and small noncoding RNAs) to enter central nervous system compartments.

Probiotics may inhibit Neurodegeneration

Probiotics are thought to influence the central nervous system and behavior via the microbiota-gut-brain axis, and researchers have suggested that they may have both preventive and therapeutic potential for Alzheimer’s disease (AD) by modulating the inflammatory process and counteracting oxidative stress, among other mechanisms.13 In the open-access Impact Journal on Aging, the researchers stated:

Dysfunction in behavior and cognition was found to be associated with dysbiosis of the GM [gut microbiota]. Activation of gut inflammation has been implicated as a possible pathogenic cofactor for cognitive decline and dementia.

Moreover, the most striking changes in the GM of AD patients are the decreased abundance of anti-inflammatory bacterial species (e.g., Bifidobacterium brevestrain A1) and the increased abundance of pro-inflammatory flora phyla (e.g., Firmicutes and Bacteroidetes).

Restoring homeostasis of GV could slow the progression of AD. Therefore, GV has been suggested as a key player in the pathogenesis of Alzheimer’s disease and could be a new potential therapeutic target for the prevention and treatment of Alzheimer’s disease.

They conducted a meta-analysis involving five studies with 297 subjects that found significant improvement in cognitive abilities and significant reductions in malondialdehyde and high-sensitivity C-reactive protein – inflammatory and oxidative biomarkers – in the probiotic groups compared with controls.

Research is still underway to determine which bacteria are most beneficial, but strain A1 of Bifidobacterium breve may be of particular use in treating Alzheimer’s disease. Using mice as a model for Alzheimer’s disease, the researchers confirmed that daily oral administration of B. breve A1 reduced cognitive dysfunction normally triggered by amyloid beta.

One of the mechanisms behind these protective effects is the suppression of amyloid beta-induced changes in gene expression in the hippocampus. In short, the bacterium had an ameliorative effect on amyloid-beta toxicity.

Other research suggests that the gut microbiota may contribute to Alzheimer’s risk through multiple pathways, including by affecting aging, diabetes, sleep and circadian rhythms.

It’s also possible, the researchers hypothesize, that decades-old factors such as diet, stress, aging and genetics combine to disrupt gut permeability and the integrity of the blood-brain barrier, allowing inflammatory agents and pathogens to enter and cause an inflammatory response that triggers a neuroinflammatory response in the brain.

“There is growing evidence that the gut microbiota interacts with AD pathogenesis by disrupting neuroinflammation and metabolic homeostasis,” they noted, adding that the gut microbiota has gone from being a forgotten organ to a potential major player in AD pathology.

Strategies for Alzheimer’s Prevention

Optimizing your gut flora is a key strategy for preventing Alzheimer’s and a number of other chronic diseases. To this end, avoid processed foods, antibiotics and antibacterial products, fluoridated and chlorinated water, and be sure to consume traditionally fermented and cultured foods, as well as high-quality probiotics when needed.

Maintaining a healthy gut is one of the parameters of a healthy lifestyle, according to Dr. Dale Bredesen, professor of molecular and medical pharmacology at the University of California, Los Angeles School of Medicine, and author of “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline.”

Bredesen’s ReCODE protocol assesses 150 factors, including biochemistry, genetics and historical imaging, known to contribute to Alzheimer’s disease. This identifies your disease subtype or combination of subtypes so that an effective treatment protocol can be established.

Time-restricted eating or fasting is another important strategy, as is reducing intake of polyunsaturated fatty acids, or PUFAs, found in vegetable oils, cooking oils, seed oils, trans fats, and vegetable oils. A ketogenic diet high in fat, moderate in protein, and low in carbohydrates is ideal for preventing the degeneration that can lead to Alzheimer’s, and it also helps nourish a healthy gut.

Overall, brain health is best promoted through a comprehensively healthy lifestyle. By using 36 healthy lifestyle parameters, Bredesen was able to reverse Alzheimer’s disease in 9 out of 10 patients.

These included exercise, a ketogenic diet, optimizing vitamin D and other hormones, getting more sleep, meditation, detoxification and avoiding gluten and processed foods. For more details, download Bredesen’s full-text case study online, which describes the entire program.

Fontes

1. Alzheimer’s Association, Facts and Figures

2. Science Daily November 13, 2020

3. J Alzheimers Dis. 2020;78(2):683-697. doi: 10.3233/JAD-200306

4. Brain Circulation 2019 Jul-Sep; 5(3): 124–129

5. Autophagy 2010 Aug 16; 6(6): 702–710

6. MIT News May 3, 2018

7. Frontiers in Aging Neuroscience November 10, 2016

8. Medical News Daily November 11, 2016

9. IntechOpen November 5, 2018, DOI: 10.5772/intechopen.79088

10. Aging (Albany NY). 2020 Feb 29; 12(4): 4010–4039, Intro

11. Aging (Albany NY). 2020 Feb 29; 12(4): 4010–4039

12. Scientific Reports October 18, 2017; 7, Article Number 13510

13. J Gerontol A Biol Sci Med Sci. 2020 Jun; 75(7): 1232–1241

14. J Gerontol A Biol Sci Med Sci. 2020 Jun; 75(7): 1232–1241, Intro, under Table 1

15. Amazônia

16. J Alzheimers Dis. 2012; 32(2):329-339

17. Aging September 27, 2014; 6(9): 707-717