Microbiota in Parkinson disease
Introduction
Neurodegenerative diseases affect the neurons and the brain in humans and animals. Parkinson’s disease (PD) is a degenerative condition that leads to dysbiosis and colonic dysfunction in patients. The PD condition is a progressively debilitating neurodegenerative condition that involves all districts of the brain-gut axis. In this case, the disease affects the central, autonomic, and enteric nervous systems. Besides, microbiome influences the bidirectional communication that takes place between the brain and the gut. The gut microbiota and the relevant metabolites interact with the brain through a series of biochemical and functional inputs. Such processes affect the homeostasis and health of the host brain. PD results from microbiota, which are biological populations of commensal, symbiotic, and pathogenic microorganisms. Understanding how microbiota causes degenerative disorders can enhance treatment methods. There is a need to explore the role of TLR4 and microbiota in PD, practical control measures, and the effectiveness of rotenone treatment. Some people argue that rotenone can effectively control the PD condition. Besides, the medication does not lead to a reduction of microbiota reduction in specific regions in the human body. Although some people argue that rotenone is an effective way to treat PD, doctors must find effective ways to control the population of microbiota as the most appropriate way to manage the condition.
Role of TLR4 and Microbiota in PD
TLRs are mammalian receptors that play a significant role in enhancing innate immunity and inflammation. Overstimulation of the innate immune system promotes systemic inflammation.[1] Some factors like gut dysbiosis cause the overstimulation of the immune systems. In this case, they influence the TLR receptors and lead to PD conditions. Humans have over ten TLRs that activate several downstream pathways of inflammation.[2] This statement implies that TLRs plays a significant role in the degeneration of the neurons. The inflammation on the immune systems affects the development of the nervous system. Therefore, TLRs plays a considerable role in the neurodegenerative condition in humans.
TLR4 remains the most effective receptor in causing neurodegenerative condition. A recent study shows that TRL1 and TLR2 activate downstream pathways that involve MyD88 and NF-kB and triggers the production of TNF.[3] Such findings show that not all TLRs causes degeneration of the neurons. However, TLR4 shows a different effect on the neuron cells. Results from an experimental study proved that TLR4 triggers microglial responses and proinflammatory cytokines release.[4] This statement implies that TLR4 influences the development of the immune systems. Such factors suggest that this receptor has a close association with the degeneration of the neurons. Most relevant cells of the nervous systems express TLRs activated by α-synuclein.[5] In practice, TLR4 triggers α-synuclein uptake in the nervous system. This case reveals that TLR4 plays a significant in promoting neurodegenerative in PD patients. Therefore, TLR4 receptors have a more substantial influence on the degeneration of the nerve cells.
Some proteins in the human body increase the microbiota population in the human gut and brain, which leads to PD. The TLR4-mediated inflammation causes soreness in the intestinal walls of the mind.[6] This statement reveals that activation of TLR4-mediated immune in the colon and brain among PD patients. The condition creates conducive conditions for the growth and existence of disease-causing organisms. The presence of the TLR4 proteins in the colon is a secondary factor in the change of intestinal microbiota.[7] The scholars maintained that TLR4 acts in collaboration with other elements to cause inflammatory conditions in various locations of the human body. The situation plays an essential role in the existence of PD conditions. The findings presented in the article supported the notion that loss of critical bacterial recognition receptor and TLR4 results in proinflammatory dysbiotic microbiota composition (Perez-Pardo et al. 841). These conditions lead to the development of neurodegenerative diseases that affects the brain and nerves system. In this case, people with higher amounts of TLR4 are likely to develop PD conditions. Thus, Perez-Pardo and colleagues show that TLR4 protein is an essential factor in the formation of degenerative diseases.
Scholars in the twenty-first century have provided adequate evidence to show that TLR4 influences the intestinal microbiota population and leads to neurodegenerative disease. A study that relied on statistical methods like correlation, analysis of variance, and graphing to examine the relationship between the TLR4 and PD.[8] The approach helped to increase the accuracy and reliability of the findings that prove a strong correlation between PD and TLR4. In this case, their results were useful in establishing why PD conditions are likely to develop PD conditions than others. Increased expression of the bacterial endotoxin-specific ligand TLR4, CD3 and T cells, and cytokine appearance in the colon is responsible for the formation of regenerative cells.[9] These factors lead to a decrease in the abundance of SCFA-producing colonic bacteria in the subject of the PD. Besides, the statement implies that the condition may lead to the development of degenerative cells ion-specific states. Therefore, TLR4 is a factor that promotes the development of PD conditions among patients today.
Recent studies show a high correlation between microbiota composition and PD conditions. Majority of the PD patients display a significant alteration in the composition of gut microbiota.[10] Such findings imply that the microbiota is a significant factor that causes degeneration of the brain matter. A study with PD mice revealed that an increase in microbial dysbiosis increases the chances of matter degradation.[11] In this case, microbiota increases proteobacteria in faecal samples of PD mice. Besides, they increased faecal short-chain fatty acids. These factors have a positive correlation with neuroinflammation among the PD mice. Therefore, microbiota composition in PD patients remains a significant cause of neuroinflammation.
Practical Control Measures and Effectiveness of Rotenone Treatment
Modern scholars have been at the forefront to examine the most effective ways that medical practitioners can use to control the PD. Rotenone treatment in TLR4-KO mice reveals lower levels of intestinal inflammation and motor dysfunction and neurodegeneration.[12] The statement implies that it is an effective method for controlling the condition where nerves tend to degenerate. However, the effectiveness of this treatment approach does not lead to better results in humans. For instance, rotenone treatment manages the PD condition in animals despite the presence of dysbiotic microbiota in TLR4-KO mice.[13] In this case, it is possible to reduce the microbiota population in specific sites in the human body where the condition may occur. However, the method may not lead to similar outcomes among humans. Therefore, rotenone is an effective method of controlling PD among wild animals but not humans.
Rotenone model of PD among humans does not lead to effective control of degenerative cells. A longitudinal study over one month did not promote active recovery among the participants in the study.[14] The researchers assessed by measuring faecal pellet output, motor functions by open-field, and pole treat every week. Besides, the examiners studied the loss of neurons from the middle brain to prove the effectiveness of the rotenone treatment methods. The findings from the study demonstrated that rotenone treatment-induced gastrointestinal and motor dysfunction among humans.[15] These conditions had a strong correlation with the composition of faecal microbiota. In this case, people who take rotenone medication to control PD condition are likely to experience an increase in the population of the bacteria and organisms that lead to degeneration of the nerve cells. However, the findings were quite different in wild animals. For instance, a study on the effect of rotenone treatment among mice specimen revealed a significant decrease in bacterial diversity in the microbiota population in their faecal samples.[16] This observation implies that rotenone treatment can reduce the level of microbiota in mice and lead to the effective management of the PD condition. Besides, these findings show a high level of consistency since they are similar to those by Perez-Pardo et al. Therefore, rotenone treatment is not an effective method to manage PD among the humans, which requires medical practitioners to device better treatment approaches.
A study that examines the process of the pathological method in a rotenone-induced model of PD and microbiome dysbiosis proposes the most effective ways that doctors can use to manage PD conditions. The scholars concluded that gut microbiome perturbation contributes to rotenone toxicity in the emergence of a PD condition in humans.[17] Using excess rotenone does not alter the composition of the microbiota in specific sites in the human body. The researcher proposes practical ways to control neurodegenerative conditions. Effective therapeutic measures focus on modifying the gut microbiota composition to delay the occurrence of degenerative diseases.[18] In this case, the doctors should find effective ways to alter the conditions that promote the growth of various organisms that affect the microbiota composition in the human body. The approach interferes with the healthy growth of the microorganisms and lowers the ability to develop degenerative growth conditions. The findings from the article help people to relate their knowledge with the relationship between microbiome imbalance and the occurrence of pathogens.[19] In this case, these scholars help to add to what other scholars developed concerning the relationship between gut microbiota composition and PD. Lower PD population does not result in extensive neuron degeneration in the human body. Thus, Yang et al. provide adequate information concerning effective methods to control the microbiota population when managing neurodegenerative conditions.
Novel treatment methods of controlling PD have the potential to provide innovative means of controlling neuron degeneration. Findings from an experimental design with male mice showed that interfering with the conditions where microbiota survives is an effective method to control the degeneration of various cells.[20] The researchers used quantitative methods to analyze the first-hand data obtained from the trials. Their findings showed that applying a collection of processes leads to better outcomes. The results obtained from the approach helped to reinforce previous knowledge concerning the relationship between gut microbiota composition and PD.[21] This statement implies that studying the structures of the microbiota in a specific organism allows health practitioners to understand the most effective approach in managing the condition. Besides, the outcomes imply that one must not rely on a single treatment approach to manage PD conditions since the microbiota population varies from one individual to the other. For instance, rotenone-induced gastrointestinal and motor dysfunction has a close correlation with changes in the composition of faecal microbiota.[22] This statement implies that different microbiota composition exists in different organisms. Every person’s case must receive individual attention and specific treatment measures. Thus, the results by Yang et al. are essential, showing the importance of using effective medication methods to control neurodegenerative conditions.
A study on the neuroprotective effects of the demethoxycurcumin (DMC) shows that rotenone treatment is an effective method for PD condition. The DMC is a treatment method that involves the injection of curcumin against rotenone-induced neurotoxicity.[23] This method involves treating the SH-SY5Y neuroblastoma cells with rotenone and DMC. The intended outcomes suggest they reduced the death of the cells that tend to have abnormal growth. The results from the study revealed that DMC pretreatment in a dose-dependent manner reduced rotenone-induced cell death in SH-SY5Y cells.[24] Such outcomes prove that treating rotenone-induced cell death is an appropriate method to reduce cases of neurodegeneration. This approach reduces the rate of deteriorating nerve cells. The findings from the current study highlights that DCM may serve as an active therapeutic agent for treating neurodegenerative diseases.(Muthu6) This statement implies that medical practitioners have a potential solution for handling degenerative conditions. However, researchers need to research on effective methods that can reduce degenerative cells. Therefore, rotenone treatment is an effective method to reduce cases of cell degeneration.
Researchers focus on effective methods of managing PD conditions. Current medications for PD improves the symptoms and does not halt the progressive.[25] This statement implies the health practitioners have not established sustainable ways to halt the degeneration of the nerves. Different therapeutic approaches do not lead to productive outcomes in PD management. Rotenone-induced experimental model of PD presents desirable issues in managing neurodegenerative conditions.(Javed4) Findings from a recent study show that the neuroprotective effect of nerolidol has effective outcomes of managing inflammatory activities. In this case, such findings support productive therapeutic potential for managing PD. Rotenone inhibits the mitochondrial complex I and inhibits cell developments.[26] Applying ROT-induced neurodegeneration in mice mediates anti-oxidative effects. Such outcomes show the possibility of managing the degeneration of nerve cells. Therefore, the current findings on rotenone medication used on mice shows the potential of managing PD conditions.
Rotenone-induced rat models show an effective way of managing PD conditions. Findings from recent studies show that caffeine has powerful therapeutic effects on rotenone-induced mice models.[27] The findings were instrumental in showing that caffeine enhances the effectiveness of the rotenone in controlling the degeneration of nerve cells. The conclusions of the study revealed that caffeine protection and treatment restored the depletion of the midbrain and striatal dopamine induced by rotenone.[28] Such outcomes proved that caffeine enhances the level of effectiveness in rotenone-induced models. In this case, caffeine reduced the rate of decline in motor activities in the PD-model mice. Combining caffeine and rotenone treatments leads to effective neuroprotection in mice models.[29] The desirable outcomes observed in mice creates a hope of developing effective methods of managing PD conditions among humans. Although doctors may not have tried the approach on humans, the current findings show a possibility of developing effective means to contain the PD condition in humans. Therefore, caffeine enhanced rotenone-based treatments may improve the overall effectiveness in controlling PD.
Medical researchers focus on ways that can enhance the outcomes in a rotenone-based treatment method for managing neurodegenerative conditions. Improving rotenone-based treatment methods with vanillin seems to increase the overall efficiency in managing PD conditions.[30] In this case, vanillin has neuroprotective nature that can enhance the adverse effects of the PD condition on neuron cells. Besides, such studies focused on finding effective ways to reduce the adverse outcomes observed in rotenone-based treatments. For instance, rotenone leads to motor, and non-motor impairments are some of the undesirable consequences caused by PD.[31] This observation implies that the need to improve the effectiveness of the rotenone-based treatment methods encourage health researchers to focus on some techniques that can enhance the overall level of outcomes. Other adverse health outcomes related to rotenone-based treatment methods include neurochemical deficits, oxidative stress and apoptosis.[32] This statement justifies the need to enhance rotenone-based treatment methods for managing the PD conditions. Thus, modern scholars focus on effective means of improving the overall ability to deal with the neurodegenerative health conditions.
Microbiota found in the brain, colon, and other body parts causes Neurodegenerative diseases like PD. The microbiota includes biological populations of commensal, symbiotic, and pathogenic microorganisms.[33] Despite the existence of this knowledge, scholars have not proposed effective methods that people may use to control PD. The knowledge gap required further research in the future, which must focus on the ways that doctors should implement to manage the PD. For instance, the fact that rotenone-treated are suitable in controlling the effects of PD in animal models does not imply the humans can record similar outcomes.[34] Such observations imply that researchers must focus on practical ways to deal with current knowledge gaps. Thus, future studies must focus on methods that a health practitioner may use to control PD.
Conclusion
The facts obtained from the two articles show that an increase in the microbiota population in specific body organs results in neurodegenerative conditions. Presence if TLR4 proteins increase the chances of developing inflammatory diseases that lead to PD. The unregulated consumption of rotenone does not reduce the microbiota composition. Therefore, people should embrace novel therapeutic methods that modify the microbiota composition in specific locations. The directions can enhance the effectiveness of the treatment methods used by health practitioners. A sufficient understanding of how microbiota causes PD can improve treatment methods. Most scholars focus on practical ways of enhancing the rotenone-based purposes of managing PD. Some of the adverse effects of the PD approach include rotenone leads to motor and non-motor impairments. The core objectives of the seminar are to explore the role of TLR4 and microbiota in PD, practical control measures, and the effectiveness of Rotenone treatment. The findings reveal that that TLR4 protein is an essential factor in the formation of degenerative conditions. Besides, the unregulated consumption of rotenone does not reduce the microbiota population in the human body. An increase in the microbiota population results in neurodegenerative diseases. Future studies must focus on particular techniques that people can use to alter the community of microbiota in sites like colon and brain.
Bibliography
Caputi, Valentina, and Maria Giron. “Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease.” International Journal of Molecular Sciences 19, no. 6 (June 6, 2018): 1689. https://doi.org/10.3390/ijms19061689.
Dhanalakshmi, Chinnasamy, Udaiyappan Janakiraman, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ameer Kalandar, Mohammed Abdul Sattar Khan, and Gilles J. Guillemin. “Vanillin Attenuated Behavioural Impairments, Neurochemical Deficits, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson’s Disease.” Neurochemical Research 41, no. 8 (April 2, 2016): 1899–1910. https://doi.org/10.1007/s11064-016-1901-5.
Dutta, Sudhir K, Sandeep Verma, Vardhmaan Jain, Balarama K Surapaneni, Rakesh Vinayek, Laila Phillips, and Padmanabhan P Nair. “Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.” Journal of Neurogastroenterology and Motility 25, no. 3 (July 1, 2019): 363–376. https://doi.org/10.5056/jnm19044.
Javed, Hayate, Sheikh Azimullah, Salema B. Abul Khair, Shreesh Ojha, and M. Emdadul Haque. “Neuroprotective Effect of Nerolidol against Neuroinflammation and Oxidative Stress Induced by Rotenone.” BMC Neuroscience 17, no. 1 (August 22, 2016). https://doi.org/10.1186/s12868-016-0293-4.
Khadrawy, Yasser A., Ahmed M. Salem, Karima A. El-Shamy, Emad K. Ahmed, Nevein N. Fadl, and Eman N. Hosny. “Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson’s Disease Induced by Rotenone.” Journal of Dietary Supplements 14, no. 5 (February 13, 2017): 553–72. https://doi.org/10.1080/19390211.2016.1275916.
Perez-Pardo, Paula, Hemraj B Dodiya, Phillip A Engen, Christopher B Forsyth, Andrea M Huschens, Maliha Shaikh, Robin M Voigt, et al. “Role of TLR4 in the Gut-Brain Axis in Parkinson’s Disease: A Translational Study from Men to Mice.” Gut 68, no. 5 (May 2019): 829–43. https://doi.org/10.1136/gutjnl-2018-316844.
Ramkumar, Muthu, Srinivasagam Rajasankar, Veerappan Venkatesh Gobi, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ameer Kalandar, and Ranganathan Chidambaram. “Neuroprotective Effect of Demethoxycurcumin, a Natural Derivative of Curcumin on Rotenone Induced Neurotoxicity in SH-SY 5Y Neuroblastoma Cells.” BMC Complementary and Alternative Medicine 17, no. 1 (April 18, 2017). https://doi.org/10.1186/s12906-017-1720-5.
Sun, Meng-Fei, Ying-Li Zhu, Zhi-Lan Zhou, Xue-Bing Jia, Yi-Da Xu, Qin Yang, Chun Cui, and Yan-Qin Shen. “Neuroprotective Effects of Fecal Microbiota Transplantation on MPTP-Induced Parkinson’s Disease Mice: Gut Microbiota, Glial Reaction and TLR4/TNF-α Signaling Pathway.” Brain, Behavior, and Immunity 70 (May 2018): 48–60. https://doi.org/10.1016/j.bbi.2018.02.005.
Wang, Yali, Wenwen Liu, Jing Yang, Fen Wang, Yizhen Sima, Zhao-min Zhong, Han Wang, Li-Fang Hu, and Chun-Feng Liu. “Parkinson’s Disease-like Motor and Non-Motor Symptoms in Rotenone-Treated Zebrafish.” NeuroToxicology 58 (January 2017): 103–9. https://doi.org/10.1016/j.neuro.2016.11.006.
Yang, Xiaodong, Yiwei Qian, Shaoqing Xu, Yanyan Song, and Qin Xiao. “Longitudinal Analysis of Fecal Microbiome and Pathologic Processes in a Rotenone Induced Mice Model of Parkinson’s Disease.” Frontiers in Aging Neuroscience 9 (January 8, 2018). https://doi.org/10.3389/fnagi.2017.00441.
[1] Sudhir K Dutta et al., “Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation,” Journal of Neurogastroenterology and Motility 25, no. 3 (July 1, 2019): 363, https://doi.org/10.5056/jnm19044.
[2] Dutta et al., “Parkinson’s Disease,” 369.
[3] Valentina Caputi and Maria Giron, “Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease,” International Journal of Molecular Sciences 19, no. 6 (June 6, 2018): 23, https://doi.org/10.3390/ijms19061689.
[4] Caputi and Giron, “Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease,” 23.
[5] Caputi and Giron, 24.
[6] Paula Perez-Pardo et al., “Role of TLR4 in the Gut-Brain Axis in Parkinson’s Disease: A Translational Study from Men to Mice,” Gut 68, no. 5 (May 2019): 829, https://doi.org/10.1136/gutjnl-2018-316844.
[7] Perez-Pardo et al., “Role of TLR4 in the Gut-Brain Axis in Parkinson’s Disease,” 841.
[8] Perez-Pardo et al., 829.
[9] Perez-Pardo et al., 831.
[10] Meng-Fei Sun et al., “Neuroprotective Effects of Fecal Microbiota Transplantation on MPTP-Induced Parkinson’s Disease Mice: Gut Microbiota, Glial Reaction and TLR4/TNF-α Signaling Pathway,” Brain, Behavior, and Immunity 70 (May 2018): 48, https://doi.org/10.1016/j.bbi.2018.02.005.
[11] Meng-Fei Sun et al., “Neuroprotective Effects of Fecal Microbiota Transplantation on MPTP-Induced Parkinson’s Disease Mice,” 48.
[12] Perez-Pardo et al., 831.
[13] Perez-Pardo et al., 829.
[14] Xiaodong Yang et al., “Longitudinal Analysis of Fecal Microbiome and Pathologic Processes in a Rotenone Induced Mice Model of Parkinson’s Disease,” Frontiers in Aging Neuroscience 9 (January 8, 2018), 1, https://doi.org/10.3389/fnagi.2017.00441.
[15] Yang et al., “Longitudinal Analysis of Fecal Microbiome and Pathologic Processes in a Rotenone Induced Mice Model of Parkinson’s Disease,” 1.
[16] Yang et al., 16.
[17] Yang et al. 1.
[18] Yang et al. 1.
[19] Yang et al., 1.
[20] Yang et al. 2.
[21] Yang et al., 2.
[22] Yang et al., 2.
[23] Muthu Ramkumar et al., “Neuroprotective Effect of Demethoxycurcumin, a Natural Derivative of Curcumin on Rotenone Induced Neurotoxicity in SH-SY 5Y Neuroblastoma Cells,” BMC Complementary and Alternative Medicine 17, no. 1 (April 18, 2017), 3, https://doi.org/10.1186/s12906-017-1720-5.
[24] Ramkumar et al., “Neuroprotective Effect of Demethoxycurcumin,” 4.
[25] Ramkumar et al., 4.
[26] Hayate Javed et al., “Neuroprotective Effect of Nerolidol against Neuroinflammation and Oxidative Stress Induced by Rotenone,” BMC Neuroscience 17, no. 1 (August 22, 2016), 4, https://doi.org/10.1186/s12868-016-0293-4.
[27] Yasser A. Khadrawy et al., “Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson’s Disease Induced by Rotenone,” Journal of Dietary Supplements 14, no. 5 (February 13, 2017): 553, https://doi.org/10.1080/19390211.2016.1275916.
[28] Khadrawy et al., “Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson’s Disease Induced by Rotenone,” 553.
[29] Khadrawy et al., 555.
[30] Chinnasamy Dhanalakshmi et al., “Vanillin Attenuated Behavioural Impairments, Neurochemical Deficits, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson’s Disease,” Neurochemical Research 41, no. 8 (April 2, 2016): 1899, https://doi.org/10.1007/s11064-016-1901-5.
[31] Dhanalakshmi et al., “Vanillin Attenuated Behavioural Impairments, Neurochemical Deficits,” 1899.
[32] [32] Dhanalakshmi et al., 1890s.
[33] Xiaodong Yang et al., “Longitudinal Analysis of Fecal Microbiome and Pathologic Processes in a Rotenone Induced Mice Model of Parkinson’s Disease,” Frontiers in Aging Neuroscience 9 (January 8, 2018), 2, https://doi.org/10.3389/fnagi.2017.00441.
[34] Yali Wang et al., “Parkinson’s Disease-like Motor and Non-Motor Symptoms in Rotenone-Treated Zebrafish,” NeuroToxicology 58 (January 2017): 103, https://doi.org/10.1016/j.neuro.2016.11.006.