Why focus on Alzheimer’s Disease Prevention?
Alzheimer’s Disease (AD) is a debilitating, progressive, neurodegenerative disease leading to loss of memory, judgment, ability to function in daily life, and death (Bonfili et al., 2017). One in nine adults over 65 years old have AD, and the prevalence is expected to double to 22% by 2040 (Alzheimer’s Association (AA), 2017). The disease has a devastating impact on the individuals and families affected by it.
The disease has a devastating impact on the individuals and families affected by it. AD also puts a huge burden on the medical system since treating and managing AD patients is complex and there are no definitive treatments available (Bonfili et al., 2017). In fact, clinical trials of over 100 drug treatments have been found to be ineffective in slowing AD progression (Wu, Cao, Chang & Juang, 2017). Even though our understanding of AD has dramatically increased over the past 20 years, the pathophysiology of AD is still being examined (AA, 2017). Investigating the mechanism of AD and finding effective therapies is of utmost importance (Bonfili et al., 2017).
What is Alzheimer’s Disease?
Alzheimer’s Disease (AD) is largely characterized by an accumulation of neurotoxic proteins in the brain, called beta-amyloid plaques and neurofibrillary tangles (Bonfili et al., 2017). The plaques accumulate between nerve cells, while tangles build up inside the nerve cells (Alzheimer’s Association (AA), 2017). Most individuals have small quantities of plaques and tangles present in their brain upon death, however, those with AD have an increased accumulation that is suspected to block communication between nerve cells and lead to the rapid cognitive decline associated the AD (AA, 2017; Cattaneo et al., 2017).
Genetics also play a role in the development of early-onset AD before the age of 40, when there is a combination of gene mutations that can lead to increased formation of amyloid-beta peptides that form amyloid-beta plaque (Bonfili et al., 2017). The pathway leading from amyloid-beta plaque deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer’s disease, however, what drives amyloid buildup is still unknown (Cattaneo et al, 2016). Scientists have observed that AD brains feature an inflammatory reaction around amyloid plaques, which could be one of the mechanisms involved in the disease progression (Cattaneo et al., 2017). Interestingly, there are certain species of gut microbiota that may promote brain inflammation, as they secrete pro-inflammatory molecules that are pathogenic to cells in the central nervous system (Cattaneo et al., 2017; Zhao, Jaber & Lukiw, 2017).
Figure 2. Gut Microbiota and Neurodegeneration
Correlation studies have shown that nervous system disorders, cognitive impairment, and AD are all associated with inflammatory molecules such as IL-6, TNF-Alfa, and inflammasome complex (NLRP3) (Bonfili et al., 2017). It has also been found that both oral probiotic therapy to reduce pro-inflammatory bacteria and the removal of gut microbiota can improve nervous system disorders and decrease neuro-inflammation (Luo et al., 2014; Toumi et al., 2014). Since diet and probiotic therapy can influence the diversity of the gut microbiota and abundance of these pro-inflammatory bacteria and molecules, it is important to further investigate this connection to fully understand the underlying mechanism with the goal of developing new therapies for AD (Dinan & Cryan, 2016).
Gut Dysbiosis and Brain Disease
There is new evidence that an imbalance or “dysbiosis” of gut microbiota is linked to dysfunction of the brain, impaired mental health, and cognitive decline associated with AD and Parkinson’s Disease (Wu et al., 2017). It is highly plausible that gut dysbiosis plays a substantial role in the pathogenesis of AD, as certain subsets of gut microbiota have been shown to release compounds that worsening the progression of AD (Dinan & Cryan, 2017). Interestingly, diets high in processed foods and low in fibre contribute to gut dysbiosis, whereas probiotic therapy has been shown to restore balance to gut bacteria (Hu et al., 2017; Bonfili et al., 2017).
Figure 3. Healthy vs. Diseased Gut Function
Research on the Gut-Brain connection
Previous research has shown that changes in the diet impact the health and diversity of the microbiome and the corresponding short-chain fatty acids (SCFA’s) and metabolites that are produced (Hu, Wang & Jin, 2016). Tillisch and colleagues (2013) found a connection between probiotics and brain health when females fed probiotic-rich fermented milk displayed changes in the activity of the resting brain, specifically in areas connected to the processing of emotions and sensations.
Observational studies have shown that alterations of gut microflora in the form of dysbiosis have the greatest impact on the brain health of vulnerable populations, such as infants, elderly and immune-compromised individuals (Dinan & Cryan, 2017). Although most data regarding the gut-brain axis emerged from pre-clinical trials, there are currently more clinical studies confirming and translating the results (Dinan & Cryan, 2017). So, this leads us to the question, can modifying gut bacteria impact the progression of Alzheimer’s Disease?
Recent Research on AD and Gut Dysbiosis
I will highly three recent studies showing the connection between gut bacteria and Alzheimer’s Disease:
Figure 4. Timeline of AD & Gut Microbiome Research
The first study by Cattaneo and colleagues (2017) conducted early in 2016 and published in 2017 examined patients with brain amyloidosis and observed a positive association with inflammatory cytokines and dysbiosis of gut microbiota. This study set the stage for further research exploring the connection of gut dysbiosis and the progression of AD.
In 2017, two animal studies were conducted for further investigation. Wu and colleagues (2017) found that infecting AD model flies with oral Enterobacteria (bacteria) to create imbalanced gut bacteria led to a significant decline in brain size, lifespan, and locomotor activity.
Next, Bonfili and collegues (2017) gave AD model mice a probiotic formula to correct dysbiosis and found reductions in cognitive decline and brain damage. This evidence indirectly supports the hypothesis that dysbiosis of gut bacteria negatively influences the progression of
This evidence indirectly supports the hypothesis that dysbiosis of gut bacteria negatively influences the progression of AD since rebalancing the gut microflora with oral probiotic therapy was shown to decrease AD progression. These results open up the possibility for investigating the administration of a novel probiotic formula such as SLAB51 and other probiotic formulas in human clinical trials to treat AD.
What does this mean for the future of treating and preventing AD?
Although these findings are preliminary and require further investigation, they are opening up the door to provide more information regarding the mechanism and connection between our gut bacteria and neurodegenerative diseases. It is vital that nutrition and healthcare professionals understand this connection and are aware of avenues to prevent and treat chronic diseases such as AD with nutrition and nutraceuticals when possible. Treating AD clearly requires a multi-faceted approach, with a health care team that is willing to find the root cause and utilize the most effective, evidence-based treatments available.
If you have any questions regarding nutrition for gut and brain health, feel free to contact us at: 204-952-7982 or email@example.com
Alzheimer’s Association (2017). What is Alzheimer’s Disease? Retrieved November 1, 2017 from https://www.alz.org/alzheimers_disease_what_is_alzheimers.asp
Bonfili, L., Cecarini, V., Berardi, S., Scarpona, S., Suchodolski, J. S., Nasuti, C., . . . Eleuteri, A. M. (2017). Microbiota modulation counteracts Alzheimer’s Disease progression influencing neuronal proteolysis and gut hormones plasma levels. Scientific Reports, 7(1) doi:10.1038/s41598-017-02587-2
Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., . . . Frisoni, G. B. (2017). Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiology of Aging, 49, 60-68. doi:10.1016/j.neurobiolaging.2016.08.019
Dinan, T. G., & Cryan, J. F. (2017). The microbiome-gut-brain axis in health and disease. Gastroenterology Clinics of North America, 46(1), 77-89. doi:10.1016/j.gtc.2016.09.007
Grenham, S., Clarke, G., Cryan, J., & Dinan, T. (2011). Brain-gut-microbe communication in health and disease. Frontiers in Physiology, 2, 94.
Hu, X., Wang, T., & Jin, F. (2016). Alzheimer’s disease and gut microbiota. Science China Life Sciences, 59(10), 1006-1023.
Jakobsson, H.E., Rodriguez-Pineiro, A.M., Schutte, A., Ermund, A., Boysen, P., Bemark, M., … & Johansson, M.E.V. (2015). The composition of the gut microbiota shapes the colon mucus barrier. EMBO Reports, 16(2), 164–177.
Luo, J., Wang, T., Liang, S., Hu, X., Li, W., Jin, F. (2014). Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Science China Life Sciences, 57(3), 327.
Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., … & Mayer, E.A. (2013). Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology, 144(7), 1394–1401.
Toumi, R., Soufli, I., Rafa, H., Belkhelfa, M., Biad, A., Touil-Boukoffa, C. (2014). Probiotic bacteria lactobacillus and bifidobacterium attenuate inflammation in dextran sulfate sodium-induced experimental colitis in mice. International journal of immunopathology and pharmacology, 27(4), 615-627.
Wu, S., Cao, Z., Chang, K. & Juang, J. (2017). Intestinal microbial dysbiosis aggravates the progression of alzheimer’s disease in drosophila. Nature Communications, 8(1) doi:10.1038/s41467-017-00040-6
Zhao, Y., Jaber, V., & Lukiw, W. J. (2017). Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer’s Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus. Frontiers in cellular and infection microbiology, 7, 318.
Zhang, R., Miller, R.G., Gascon, R., Champion, S., Katz, J., Lancero, M., … & McGrath, M.S. (2009). Circulating endotoxin and systemic immune activation in sporadic amyotrophic lateral sclerosis (sALS). Journal of Neuroimmunology, 206(1), 121–124.