Neurodegenerative diseases (NDs) are a branch of neural diseases that involve the progressive functional loss of neurons in the central nervous system (CNS) and peripheral nervous system (PNS) that overall leads to long-term motor and cognitive impairments. There are several risk factors that influence the development of neurodegenerative diseases, such as genetic factors, as well as environmental factors that may progress the pathologies of the disease. One area of study that is being researched as another potential factor is an organism’s microbiome and how it may have alterations as a result of the previously mentioned factors. Although the mechanism of this effect is not fully understood, two NDs, Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), have presented with modified microbiomes compared to normal subjects. Alzheimer’s Disease is characterized by the progressive loss of cognition, memory, and motor ability. The hallmark of AD is intracellular hyperphosphorylated tau tangles and the accumulation of extracellular Aβ plaques in the brain, along with other neuropathological symptoms such as neuronal loss and brain atrophy. Parkinson’s Disease, on the other hand, is a multifactorial ND in the sense that it can result from a combination of environmental and genetic factors. Its signature feature is neurotoxic alpha-synuclein inclusions from striatal dopaminergic motor deficits and cell death.
The gastrointestinal tract is home to millions of trillions of microorganisms that collectively make up the gut microbiota, which is essential to the function and development of the CNS and PNS for several organisms. Gut microbiota activity changes over one’s lifespans, similar to aging-related disorders that affect immune function, metabolic activity and overall longevity. The process of aging and its relation to the microbiome is typically accompanied by impaired digestion, disruptive nutrient absorption, chronic inflammation, and increased intestinal permeability. Interestingly, social factors have also been associated with altered microbiota. For example, married couples have had relatively more diverse taxa in their microbiome compared to single individuals.
In AD, manipulations of the microbiome, as a regulator of the neuroimmune system have been associated with changes in learning and memory related behavior. In most notable cases, an increase of bacterial abundance has been correlated with increased changes in cerebrospinal fluid (CSF) markers that progressively lead to increased amyloid burden in the brain. Certain strains of bacteria, such as Alistipes, Odoribacter, Paraprevotella, and others were negatively associated with tau pathology in the brain, while strains such as Bacteroides, Parabacteriodes, and Clostridium_innocuum were positively correlated. The altered states of these microbiomes lead to neuroinflammation that can further increase the severity of Aβ pathology.
Furthermore, in PD, the evidence is in the involvement of the microbiota’s pathogenesis is linked to microbial regulation in intestinal inflammation. Many Parkinson’s patients face GI disturbances (chronic gastritis or constipation) years in advance to the onset of motor symptoms, thus suggesting the exploration of these microbial factors may provide insight into early features of PD. Similar to AD, there are certain combinations of microorganisms that can lead to a greater aggregation of alpha-synuclein that leads to neuronal inclusions characterized by the misfolding of the alpha-synuclein protein.
The implications of the research conducted in this article is similar to that of Dr. Martha Hotz Vitaterna’s study, “A Prebiotic Diet Alters the Fecal Microbiome and Improves Sleep in Response to Sleep Disruption in Rats.” In this study, the microbiome has been shown to have effects on the circadian rhythms in mice in regard to sleep deprivation. Mice that were given the prebiotic diet, GOX/PDX had lower levels of sleep deprivation as well as greater NREM sleep. The alpha diversity level of the microbiome had shown that less alpha diversity was related to greater health risks, which reflects the current study’s theory of more diverse microbiomes can be associated in relatively healthier individuals.
We have been told time and time again “You are what you eat,” and studies such as Dr. Vitaterna’s and the current study being research have shown that may be closer to the truth than we know. Whether it's a minor modification or a more drastic one, it is likely that some part of our microbiota is bound to change from a culmination of both genetic and environmental factors. Such developments can provide more insight into the pathologies of several neurodegenerative diseases, as well as potential treatments.
References
Bowers, S. J., Summa, K. C., Thompson, R. S., González, A., Vargas, F., Olker, C., Jiang, P., Lowry, C. A., Dorrestein, P. C., Knight, R., Wright, K. P., Fleshner, M., Turek, F. W., & Vitaterna, M. H. (2022). A prebiotic diet alters the fecal microbiome and improves sleep in response to sleep disruption in rats. Frontiers in Neuroscience, 16. https://doi.org/10.3389/fnins.2022.889211
Fang, P., Kazmi, S. A., Jameson, K. G., & Hsiao, E. Y. (2020). The microbiome as a modifier of Neurodegenerative Disease Risk. Cell Host & Microbe, 28(2), 201–222. https://doi.org/10.1016/j.chom.2020.06.008
No comments:
Post a Comment