Scientists consider causal connection to be a major breakthrough
New research from Sweden’s Lund University shows that intestinal bacteria accelerate the development of Alzheimer’s disease (AD). According to the researchers, these findings open the door to new opportunities to prevent and treat the disease.1
“The results mean that we can now begin researching ways to prevent [AD] and delay the onset. We consider this to be a major breakthrough [emphasis added].” The foregoing statement was made by lead researcher Frida Fåk Hållenius, suggesting that what goes on in our guts is reflected by what goes on in our brains.1
Fewer Bacteria Reduce Amyloid Plaque in the Brain
We’ve know about a gut-brain (bacteria-AD) connection for several years now and have published several articles about it, starting with “Ulcer Bug Eradication Empowers Galantamine” which appeared in the March 2014 issue of Life Enhancement (more on this later).
In the Swedish paper, researchers studied bacterially compromised mice and found that mice suffering from the mouse equivalent of AD have a different composition of gut bacteria compared to mice that are healthy and without AD.
Furthermore, the researchers also studied AD in mice that completely lacked gut bacteria—finding they had significantly lower levels of beta-amyloid plaque that are associated with the development of AD.
More Bacteria Means More Plaque
When these bacteria-free mice were given intestinal bacteria from mice with AD, Dr. Hållenius and colleagues saw that the mice developed more beta-amyloid plaques than when they were given bacteria from healthy mice.
“Our study is unique as it shows a direct causal link between gut bacteria and [AD]. It was striking that the mice which completely lacked bacteria developed much less plaque in the brain,” said Dr. Hållenius.2
“Our results indicate a microbial involvement in the development of beta-amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases,” quoting the paper.1
Indeed, the association of bacterial taxa (a taxonomic category, as a species or genus) with cerebral pathology observed in mice implies that specific microbes may be involved in progression of cerebral beta-amyloidosis and that this may lead to the onset or progression of AD.
Microbiota Contribute to Neurological and Neurodegenerative Diseases
“Obviously, the clinical translation of these preclinical results bears the potential for opening a new area for the treatment and prevention of AD pathology and ultimately other neurodegenerative disorders,” wrote the Swedish researchers.
To this they added that their findings foster support for a developing view that microbiota contribute to the development of a wide range of neurological and neurodegenerative diseases that goes “well beyond metabolic syndrome, diabetes and obesity.”
In their study, Hållenius et al measured the relative abundance of microbes in healthy mice and those with a mouse model of Alzheimer’s disease known as APP transgenic mice. Microscopic examination of their tissue shows that APP transgenic mice have an accumulation of amyloid beta (Aβ) in plaques from an early age; these plaques are invariably surrounded by activated inflammatory cells such as astrocytes and microglia, as is common in the AD brain.
pyloriseem to be the most
important member of the gastric
microbiota with the highest relative
abundance when present, but when it
is absent, the stomach has a diverse
Which Bacteria Were Abundant?
The researchers found that the abundance of at least two major phyla (Firmicutes and Bacteroidetes) in the fecal microbiota was significantly altered in transgenic mice compared to healthy counterparts (non-transgenic wild-type mice).
At genus level, Allobaculum and Akkermansia were decreased and unclassified genera of Rikenellaceae and S24-7 increased, said the research team.
Figure 1. A protected stomach protects the brain.
Germ Free Colonization Led to Drastic Reduction of Cerebral Aβ
“Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota,” wrote the researchers.
They added that colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased amyloid plaques and signs of Alzheimer’s, while colonization with microbiota from wild-type mice did not lead to increases in plaques.
To further study the link between the microbiome and cerebral β-amyloidosis, the researchers generated transgenic mice without gastro-intestinal microbiota. “Remarkably, we observed significant alterations in the brain’s immune response in [AD-associated mutations transgenic] mice,” wrote the researchers.
“Our study strongly argues for a role of gastro-intestinal microbes in the development of cerebral Aβ amyloidosis [emphasis added].”
“Our study strongly argues for a role
of gastro-intestinal microbes in the
development of cerebral Aβ
The Modulation of the Gut Microbiota
The Swedish team, along with other researchers in Europe, will continue to study the role of bacteria in the development of AD, and test new types of preventive and therapeutic strategies based on the modulation of the gut microbiota through diet and new types of probiotics.
This study is not the first. There have been other studies showing a connection between gut bacteria and Alzheimer’s. For example, in a 2014 paper published in the journal Frontiers in Cellular Neuroscience, researchers listed 10 different ways that the microbiome may contribute to the development of AD, including fungal and bacterial infections in the intestinal tract and increased permeability of the blood-brain barrier.4
Mastic Eradicates H. pylori
Returning to the “Ulcer Bug Eradication Empowers Galantamine” article mentioned above, a paper titled “Eradication of Helicobacter pylori Is Associated with the Progression of Dementia: A Population-Based Study” examined the impact of a leading gut bacteria.
Helicobacter pylori (Hp) is a bacterium with a Nobel Prize pedigree, in a manner of speaking. Identified in 1982 by Australian scientists Barry Marshall and Robin Warren to be present in patients with chronic gastritis and gastric ulcers—conditions that were not previously believed to have a microbial cause—Dr. Marshall put his hypothesis to the test.
In 1984, Marshall drank a Petri dish containing cultured Hp, anticipating that he would develop an ulcer in time, perhaps years later. Instead, within days he developed all the signs of an ulcer in the making, but by treating himself with antibiotics he reversed his conditions. This was a revolutionary step in gastroenterology, reversing decades of medical doctrine, which held that ulcers were caused by stress, spicy foods, and too much acid. For this discovery, Drs. Marshall and Warren justly received a Nobel Prize in 2005.
This was a revolutionary step in
gastroenterology, reversing decades of
medical doctrine, which held that
ulcers were caused by stress, spicy
foods, and too much acid.
Ulcers Increase the Progression of Alzheimer’s Disease
With regard to Hp research, perhaps there is another Nobel Prize in the making. Over the past decade, research indicates that ulcers caused by Hp may increase the progression of dementia in AD. In the most recent study, Chinese researchers from Taiwan examined 30,142 patients with both AD and peptic ulcers.5 They found that after eradication of the patient population’s Hp, the risk of AD progression was decreased. Before Hp eradication, among AD patients with peptic ulcers in the study, their AD got worse. However, after eradication, the efficacy of the acetylcholinesterase inhibitors (including galantamine) improved, compared to those with no eradication!
This was not the first time the relationship between Hp and AD has been studied. More than 12 years ago in 2004, a scientific paper found a possible link between Hp and AD.6Two years later, researchers hypothesized that cholesterol glucosides arising from Hpinfection may act as neurotoxins, promoting the degeneration of the dopaminergic neurons affected in Parkinson’s disease.7 Then in 2006, an article in the journal Neurology reported that in 50 patients with AD (as compared to controls without AD) the prevalence of Hp infection was significantly greater (88% in those with AD and 46.7% in controls).8
Of great interest, in 2007 researchers found a connection between Hp and mild cognitive impairment (MCI). MCI is considered an early symptom and prodromal phase of AD.9 The prevalence of Hp infection was 88.9% (56/63) in MCI patients and 48.6% (17/35) in anemic controls, as confirmed by biopsy.
After eradication, the efficacy of the
(including galantamine) improved,
compared to those with no
Altogether, over the years, there have been few clinical investigations of the Hp/AD relationship. So the appearance of a paper in the well-regarded Journal of Neurology in 2009 stepped up the pace of discovery. This research suggested that in patients diagnosed with AD, eradication of Hp can actually improve cognitive function to a significant degree.10
Mastic Can Eradicate Hp
If you are currently taking galantamine, for preventive or treatment purposes, based on the results of the Taiwan study, it may be a good idea to take care of any Hp infection with mastic, which has been shown to eradicate Hp, but without any of the side effects of the antibiotic treatment. Also, mastic may be taken at a maintenance level so reinfection is less likely. (See “Mastic: Curtains for Ulcer-Causing Bacteria” in the January, 2010 issue).
The major take home point is the finding that the eradication of Hp decreases AD and enhances the beneficial effects of acetylcholinesterase inhibitors such as galantamine.
So there you have it. Eradicating Hp may be as important or more so than getting rid of other bacteria in the gut, and a key to reducing Alzheimer’s via mastic and galantamine.