For patients with neurodegenerative disorders and their families, the possibility of effective management options provides a sense of hope in an otherwise challenging and frustrating situation. Medical professionals can offer advice about drugs and lifestyle changes that may help, but in many cases, the available therapeutics have only minimal effects, and the “bad days” increasingly outweigh the good ones as the disease progresses. As a result, patients are continuing to call for the development of better therapies, and the research community is responding.
So far, researchers have developed a variety of pharmacological drugs that may help patients manage symptoms—including dopamine agonists, synthetic dopamine, anticholinergics, and enzyme inhibitors, among others—as well as non-pharmacological therapeutic options, such as brain training games, social stimulation, and physical exercise. Nevertheless, while some patients respond remarkably well to these therapies, there are still patients for whom the effects are moderate, mild, or even nonexistent. There are also patients whose symptoms improve because of pharmacological treatments, but they experience side effects that negatively affect their quality of life. Therefore, the quest for effective strategies for the management of neurodegenerative disorders continues.
One emerging strategy is to use dietary supplements to aid in the management of neurodegenerative disorders. While comprehensive clinical trials are lacking, preliminary research in animal models suggests that there may be benefits to taking supplements that modulate the gut microbiome or directly introduce metabolites of gut bacteria, such as short-chain fatty acids. Based on these early findings, practitioners and patients may start considering taking a dietary supplement as a viable alternative for the management of neurodegenerative disorders.
Probiotic Supplementation and Neurodegenerative Disorders: A Landmark Nature Paper
One of the most intriguing studies on the potential benefits of dietary supplements for the management of neurodegenerative disorders was published in Nature Scientific Reports in May 2017. In this study, a group of researchers from the University of Camerino in Italy examined the relationship between probiotic supplementation and the physiological and symptomatic manifestations of Alzheimer’s disease. Their work was premised on the notion that gut bacteria and their metabolites are involved in the regulation of several key neurochemical pathways, and the results of the study built on this idea by showing how microbiome modulation could directly impact physiological signs of neurodegeneration in animal models.
The researchers conducted their study on mouse models of Alzheimer’s disease while they were in the early stages of the disease. They treated the mice with a novel probiotic formulation that included lactic acid bacteria and bacteria from the genus Bifidobacterium. The choice of these genera for the probiotic formulation is notable because both Bifidobacterium and lactic acid bacteria are known to be involved in the production of a key metabolite: butyric acid. This compound is produced when bacteria in the gut metabolize fiber, and it plays a role in a wide range of body processes, including epigenetic regulation, energy metabolism, and the activation of critical protein signaling and communication pathways.
Results and Implications for Dietary Supplementation as a Neurodegenerative Disorder Management Strategy
One of the most significant findings of the study was that the mouse models that took the probiotic formulation demonstrated significantly less cognitive decline than the controls. The researchers used two types of tests (novel object recognition and passive avoidance tests), both of which are widely used in the field for measuring the functions of the hippocampus and the amygdala, the two parts of the brain that are implicated in cognitive decline associated with neurodegenerative disorders. The researchers attributed the lack of cognitive decline in the mice that took probiotic supplements to decreases in brain damage and a reduction in the accumulation of amyloid beta aggregates—that is, clumps of misfolded proteins that are a well-known hallmark of neurodegenerative disease.
In the study, the researchers elucidated a specific mechanistic explanation for the decrease in beta-amyloid plaques. In the mice that took the probiotic supplement, they observed a partial restoration of the function of two proteolytic pathways that are impaired in mouse models of Alzheimer’s disease. Proteolytic pathways are pathways that degrade proteins, so when they are not functioning normally, it can lead to the buildup of amyloid beta aggregates, which can, in turn, contribute to the onset and exacerbation of neurodegeneration. Taking the probiotic supplement actually improved the functioning of those pathways, and the researchers were able to directly link this physiological result to the cognitive symptoms displayed by the mouse models.
The third important result of the study was that taking the probiotic had a modulating effect on the levels of inflammatory cytokines and neurodegeneration-related hormones in the blood. Inflammation is known to be an important factor in neurodegenerative disease progress, and the hormones they found are currently being considered by researchers as therapeutic targets for future Alzheimer’s disease treatments. Overall, taken together, the researchers’ results clearly suggest that probiotic supplements may have multiple benefits for patients with neurodegenerative disorders.
Looking Beyond Probiotics
While the results of the study provides significant support for the use of probiotics, they also suggest that other supplements may have a beneficial impact. In particular, butyric acid may be a potentially useful dietary supplement for patients who are looking for a neurodegenerative disease management option. The study showed that when the mouse models took the probiotic supplement, there were statistically significant increases in all three of the short chain fatty acids commonly found in the gut: butyric acid, propionic acid, and acetic acid. Ultimately, this came as no surprise, since (as previously noted), both lactic acid bacteria and Bifidobacterium are known to be involved in the production of butyric acid in the gut. However, this study offers new insight because it associates increases in the levels of these compounds with physiological and behavioral improvements in mouse models of Alzheimer’s disease, suggesting that a direct introduction of butyric acid through a supplement has the potential to produce similar results.
As more studies like this enter the research pipeline, the relationships between the microbiome and neurodegenerative disorders will become increasingly clear. Clinical trials may also be able to shed more light on the relative efficacy of different probiotic formulations and dietary supplements like butyric acid. Until then, patients and practitioners may consider both types of supplements as possibilities when exploring possible strategies for the management of neurodegenerative disorders.
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