Parkinson’s disease and the Interaction of Photobiomodulation, the Microbiome, and Antibiotics: A Case Series A Case Series
Article Sidebar
Published
Jan 30, 2024
Downloads
Download data is not yet available.
Submit your own article
Register as an author to reserve your spot in the next issue of the Medical Research Archives.
Author RegistrationJoin the Society
The European Society of Medicine is more than a professional association. We are a community. Our members work in countries across the globe, yet are united by a common goal: to promote health and health equity, around the world.
Join Europe’s leading medical society and discover the many advantages of membership, including free article publication.
MembershipMain Article Content
Abstract
It is apparent that there is a close association between the gut microbiome and Parkinson’s disease, with many patients having gut symptoms. Gut microbiome dysfunction may be related to instigation and progression of Parkinson’s disease in many patients. There is also evidence that disrupting the gut microbiome, such as with antibiotics, can increase the risk of developing Parkinson’s disease. Photobiomodulation has the potential to alleviate the symptoms of Parkinson’s disease in both animal models and in humans and has also been shown to alter the microbiome in a mouse model. Here we assessed the interaction between photobiomodulation and the gut microbiome in four people with Parkinson’s disease, three of whom had participated in clinical trials and two of whom were prescribed antibiotics during the photobiomodulation treatment.
Patients were treated three times per week using infrared laser treatment to the abdomen and neck with or without LED treatment to the head. Gastrointestinal symptoms were assessed prior to treatment and after 4 weeks and 12 weeks of photobiomodulation therapy and microbiome status was assessed in 3 of the 4 patients. Outcome measures included motor signs and patient-reported non-motor symptoms including symptoms of constipation/diarrhea/gastric motility, and abdominal pain, as well as phylogenetic analysis of microbiome diversity.
Participants in this case series were seen as good responders to photobiomodulation treatment, with improvements in motor signs and non-motor symptoms. Gastrointestinal symptoms, including irritable bowel symptoms were improved, and microbiome analysis indicated a generally positive change in bacterial diversity. Antibiotic use during the photobiomodulation treatment had a negative effect on motor and non-motor improvements, as well as disrupting the microbiome.
Results of this study suggest that photobiomodulation may have a role in the improvement of the gut microbiome, which could be advantageous in the treatment of Parkinson’s disease, considering the strong microbiome-gut-brain-axis in the disease.
Article Details
How to Cite
BICKNELL, Brian et al.
Parkinson’s disease and the Interaction of Photobiomodulation, the Microbiome, and Antibiotics: A Case Series.
Medical Research Archives, [S.l.], v. 12, n. 1, jan. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4929>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i1.4929.
Section
Case Series
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol. Jun 2010;67(6):715-25. doi:10.1002/ana.21995
2. Bicknell B, Liebert A, Borody T, Herkes G, McLachlan C, Kiat H. Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome. International Journal of Molecular Sciences. 2023;24(11):9577.
3. Roy Sarkar S, Banerjee S. Gut microbiota in neurodegenerative disorders. Journal of Neuroimmunology. 2019/03/15/ 2019;328:98-104. doi:https://doi.org/10.1016/j.jneuroim.2019.01.004
4. Scheperjans F, Derkinderen P, Borghammer P. The Gut and Parkinson's Disease: Hype or Hope? Journal of Parkinson's disease. 2018;8(s1):S31-S39. doi:10.3233/JPD-181477
5. Kaye J, Gage H, Kimber A, Storey L, Trend P. Excess burden of constipation in Parkinson's disease: a pilot study. Movement disorders: official journal of the Movement Disorder Society. 2006;21(8):1270-1273.
6. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease. Movement Disorders. 2015;30(12):1600-1611.
7. Borghammer P, Van Den Berge N. Brain-first versus gut-first Parkinson’s disease: a hypothesis. Journal of Parkinson's disease. 2019;9(s2):S281-S295.
8. Horsager J, Knudsen K, Sommerauer M. Clinical and imaging evidence of brain-first and body-first Parkinson's disease. Neurobiology of disease. 2022;164:105626.
9. Horsager J, Andersen KB, Knudsen K, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020;
10. Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH. Is alpha‐synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Movement Disorders. 2012;27(6):716-719.
11. Chen S-J, Lin C-H. Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis. Journal of Biomedical Science. 2022/07/27 2022;29(1):54. doi:10.1186/s12929-022-00839-6
12. Skjærbæk C, Knudsen K, Horsager J, Borghammer P. Gastrointestinal Dysfunction in Parkinson's Disease. J Clin Med. Jan 31 2021;10(3)doi:10.3390/jcm10030493
13. Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell. 2016;167(6):1469-1480. e12.
14. Cirstea MS, Yu AC, Golz E, et al. Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson's Disease. Movement Disorders. 2020;
15. Lin C-H, Chen C-C, Chiang H-L, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. Journal of neuroinflammation. 2019;16(1):1-9.
16. Hill‐Burns EM, Debelius JW, Morton JT, et al. Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome. Movement Disorders. 2017;32(5):739-749.
17. Wallen ZD, Demirkan A, Twa G, et al. Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Nature Communications. 2022/11/15 2022;13(1):6958. doi:10.1038/s41467-022-34667-x
18. Toh TS, Chong CW, Lim S-Y, et al. Gut microbiome in Parkinson's disease: New insights from meta-analysis. Parkinsonism & Related Disorders. 2022;94:1-9.
19. Baldini F, Hertel J, Sandt E, et al. Parkinson's disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC biology. 2020;18(1):62-62. doi:10.1186/s12915-020-00775-7
20. Adams-Carr KL, Bestwick JP, Shribman S, Lees A, Schrag A, Noyce AJ. Constipation preceding Parkinson's disease: a systematic review and meta-analysis. Journal of Neurology, Neurosurgery & Psychiatry. 2016;87(7):710-716. doi:10.1136/jnnp-2015-311680
21. Villumsen M, Aznar S, Pakkenberg B, Jess T, Brudek T. Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977–2014. Gut. 2019;68(1):18-24.
22. Fu P, Gao M, Yung KKL. Association of intestinal disorders with Parkinson’s disease and Alzheimer’s disease: A systematic review and meta-analysis. ACS Chemical Neuroscience. 2019;11(3):395-405.
23. Liu B, Sjölander A, Pedersen NL, et al. Irritable bowel syndrome and Parkinson’s disease risk: register-based studies. npj Parkinson's Disease. 2021;7(1):1-7.
24. Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register–based matched-cohort study. Neurology. 2017;88(21):1996-2002.
25. Dutta SK, Verma S, Jain V, et al. Parkinson’s disease: the emerging role of gut dysbiosis, antibiotics, probiotics, and fecal microbiota transplantation. Journal of neurogastroenterology and motility. 2019;25(3):363.
26. Parkinson J. An essay on the shaking palsy. The Journal of neuropsychiatry and clinical neurosciences. 2002;14(2):223-236.
27. Pang SY-Y, Ho PW-L, Liu H-F, et al. The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease. Translational Neurodegeneration. 2019/08/16 2019;8(1):23. doi:10.1186/s40035-019-0165-9
28. Paul KC, Ritz B. Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease. Environment international. 2022;170:107613.
29. Darweesh SK, Vermeulen R, Bloem BR, Peters S. Exposure to Pesticides Predicts Prodromal Feature of Parkinson's Disease: Public Health Implications. 2022;
30. Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3-s8. doi:10.3233/jpd-181474
31. Puigbò P, Leino LI, Rainio MJ, Saikkonen K, Saloniemi I, Helander M. Does Glyphosate Affect the Human Microbiota? Life. 2022;12(5):707.
32. Ruuskanen S, Fuchs B, Nissinen R, et al. Ecosystem consequences of herbicides: the role of microbiome. Trends in Ecology & Evolution. 2023;38(1):35-43. doi:10.1016/j.tree.2022.09.009
33. Caballero M, Amiri S, Denney JT, Monsivais P, Hystad P, Amram O. Estimated residential exposure to agricultural chemicals and premature mortality by Parkinson’s disease in Washington state. International journal of environmental research and public health. 2018;15(12):2885.
34. Chen H-Q, Gong J-Y, Xing K, Liu M-Z, Ren H, Luo J-Q. Pharmacomicrobiomics: Exploiting the Drug-Microbiota Interactions in Antihypertensive Treatment. Review. Frontiers in Medicine. 2022-January-19 2022;8 doi:10.3389/fmed.2021.742394
35. Konstantinidis T, Tsigalou C, Karvelas A, Stavropoulou E, Voidarou C, Bezirtzoglou E. Effects of antibiotics upon the gut microbiome: a review of the literature. Biomedicines. 2020;8(11):502.
36. Ternák G, Németh M, Rozanovic M, Márovics G, Bogár L. Antibiotic Consumption Patterns in European Countries Are Associated with the Prevalence of Parkinson’s Disease; the Possible Augmenting Role of the Narrow-Spectrum Penicillin. Antibiotics. 2022;11(9):1145.
37. Mertsalmi TH, Pekkonen E, Scheperjans F. Antibiotic exposure and risk of Parkinson's disease in Finland: A nationwide case‐control study. Movement Disorders. 2020;35(3):431-442.
38. Pal G, Bennett L, Roy J, et al. Antibiotic exposure and risk of Parkinson's disease in the United Kingdom: A case-control study (P5-11.001). Neurology. 2023;100(17 Supplement 2):0077. doi:10.1212/wnl.0000000000201752
39. Liang X, Bushman FD, FitzGerald GA. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proceedings of the National Academy of Sciences. August 18, 2015 2015;112(33):10479-10484. doi:10.1073/pnas.1501305112
40. Montagner A, Korecka A, Polizzi A, et al. Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Scientific Reports. 2016;6:20127. doi:10.1038/srep20127
41. Leone V, Gibbons SM, Martinez K, et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell host & microbe. 2015;17(5):681-689.
42. Dompe C, Moncrieff L, Matys J, et al. Photobiomodulation-Underlying Mechanism and Clinical Applications. J Clin Med. Jun 3 2020;9(6)doi:10.3390/jcm9061724
43. Glass GE. Photobiomodulation: the clinical applications of low-level light therapy. Aesthetic Surgery Journal. 2021;41(6):723-738.
44. González-Muñoz A, Cuevas-Cervera M, Pérez-Montilla JJ, et al. Efficacy of Photobiomodulation Therapy in the Treatment of Pain and Inflammation: A Literature Review. Healthcare. 2023;11(7):938.
45. Naeser MA, Martin PI, Ho MD, et al. Transcranial Photobiomodulation Treatment: Significant Improvements in Four Ex-Football Players with Possible Chronic Traumatic Encephalopathy. Journal of Alzheimer's Disease Reports. 2023;7:77-105. doi:10.3233/ADR-220022
46. Figueiro Longo MG, Tan CO, Chan S-t, et al. Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury: A Randomized Clinical Trial. JAMA Network Open. 2020;3(9):e2017337-e2017337. doi:10.1001/jamanetworkopen.2020.17337
47. Naeser MA, Martin PI, Ho MD, et al. Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury. Photomed Laser Surg. Dec 2016;34(12):610-626. doi:10.1089/pho.2015.4037
48. Naeser MA, Ho MD, Martin PI, Hamblin MR, Koo B-B. Increased functional connectivity within intrinsic neural networks in chronic stroke following treatment with red/near-infrared transcranial photobiomodulation: case series with improved naming in aphasia. Photobiomodulation, Photomedicine, and Laser Surgery. 2020;38(2):115-131.
49. Stephan W, Banas LJ, Hamblin MR. Treatment Efficacy of Photobiomodulation for Moderate and Advanced Dementia or Alzheimer’s Disease: Case Studies. Advances in Alzheimer's Disease. 2022;11(4):39-47.
50. Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L. Significant improvement in cognition in mild to moderately severe dementia cases treated with transcranial plus intranasal photobiomodulation: case series report. Photomedicine and laser surgery. 2017;35(8):432-441.
51. Herkes G, McGee C, Liebert A, et al. A novel transcranial photobiomodulation device to address motor signs of Parkinson’s disease: a parallel randomised feasibility study. EClinicalMedicine. 2023;66
52. Liebert A, Bicknell B, Laakso E-L, et al. Remote Photobiomodulation Treatment for the Clinical Signs of Parkinson's Disease: A Case Series Conducted During COVID-19. Photobiomodulation, photomedicine, and laser surgery. 2022;40(2):112-122.
53. Liebert A, Bicknell B, Laakso E-L, et al. Improvements in the clinical signs of Parkinson’s disease using photobiomodulation: a 3-year follow-up case series. Medical Research Archives. 2023;11(3)
54. Liebert A, Bicknell B, Laakso EL, et al. Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study. BMC Neurology. 2021/07/02 2021;21(1):256. doi:10.1186/s12883-021-02248-y
55. Shaw VE, Spana S, Ashkan K, et al. Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment. Journal of Comparative Neurology. 2010;518(1):25-40.
56. Peoples C, Spana S, Ashkan K, et al. Photobiomodulation enhances nigral dopaminergic cell survival in a chronic MPTP mouse model of Parkinson’s disease. Parkinsonism & related disorders. 2012;18(5):469-476.
57. Moro C, Torres N, El Massri N, et al. Photobiomodulation preserves behaviour and midbrain dopaminergic cells from MPTP toxicity: evidence from two mouse strains. BMC neuroscience. 2013;14(1):1-9.
58. Reinhart F, El Massri N, Johnstone DM, et al. Near-infrared light (670 nm) reduces MPTP-induced parkinsonism within a broad therapeutic time window. Experimental brain research. 2016;234(7):1787-1794.
59. Gordon LC, Martin KL, Torres N, et al. Remote photobiomodulation targeted at the abdomen or legs provides effective neuroprotection against parkinsonian MPTP insult. European Journal of Neuroscience. 2023;57(9):1611-1624.
60. Johnstone D, El Massri N, Moro C, et al. Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism–an abscopal neuroprotective effect. Neuroscience. 2014;274:93-101.
61. Kim B, Mitrofanis J, Stone J, Johnstone DM. Remote tissue conditioning is neuroprotective against MPTP insult in mice. IBRO Reports. 2018;4:14-17.
62. Bicknell B, Liebert A, Johnstone D, Kiat H. Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases. Lasers in medical science. 2018;34(2):317-327.
63. Salehpour F, Sadigh-Eteghad s, Mahmoudi J, Kamari F, Cassano P, Hamblin M. Photobiomodulation Therapy for Parkinson’s Disease. Photobiomodulation for the Brain Photobiomodulation Therapy in Neurology andNeuropsychiatry. Springer; 2023:chap 10. Synthesis Lectures on Biomedical Engineering.
64. Bicknell B, Liebert A, McLachlan CS, Kiat H. Microbiome Changes in Humans with Parkinson’s Disease after Photobiomodulation Therapy: A Retrospective Study. Journal of Personalized Medicine. 2022;12(1):49.
65. Bicknell B, Laakso E-L, Liebert A, Kiat H. Modifying the microbiome as a potential mechanism of photobiomodulation: A case report. Photobiomodulation, photomedicine, and laser surgery. 2022;40(2):88-97.
66. Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nature Biotechnology. 2019/08/01 2019;37(8):852-857. doi:10.1038/s41587-019-0209-9
67. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Molecular biology and evolution. 2013;30(4):772-780.
68. Price MN, Dehal PS, Arkin AP. FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments. PLOS ONE. 2010;5(3):e9490. doi:10.1371/journal.pone.0009490
69. Bokulich NA, Kaehler BD, Rideout JR, et al. Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2’s q2-feature-classifier plugin. Microbiome. 2018/05/17 2018;6(1):90. doi:10.1186/s40168-018-0470-z
70. McDonald D, Price MN, Goodrich J, et al. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. The ISME Journal. 2012/03/01 2012;6(3):610-618. doi:10.1038/ismej.2011.139
71. Bokulich NA, Dillon MR, Zhang Y, et al. q2-longitudinal: Longitudinal and Paired-Sample Analyses of Microbiome Data. mSystems. 2018;3(6):e00219-18. doi:10.1128/mSystems.00219-18
72. Wallen ZD, Appah M, Dean MN, et al. Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. npj Parkinson's Disease. 2020/06/12 2020;6(1):11. doi:10.1038/s41531-020-0112-6
2. Bicknell B, Liebert A, Borody T, Herkes G, McLachlan C, Kiat H. Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome. International Journal of Molecular Sciences. 2023;24(11):9577.
3. Roy Sarkar S, Banerjee S. Gut microbiota in neurodegenerative disorders. Journal of Neuroimmunology. 2019/03/15/ 2019;328:98-104. doi:https://doi.org/10.1016/j.jneuroim.2019.01.004
4. Scheperjans F, Derkinderen P, Borghammer P. The Gut and Parkinson's Disease: Hype or Hope? Journal of Parkinson's disease. 2018;8(s1):S31-S39. doi:10.3233/JPD-181477
5. Kaye J, Gage H, Kimber A, Storey L, Trend P. Excess burden of constipation in Parkinson's disease: a pilot study. Movement disorders: official journal of the Movement Disorder Society. 2006;21(8):1270-1273.
6. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease. Movement Disorders. 2015;30(12):1600-1611.
7. Borghammer P, Van Den Berge N. Brain-first versus gut-first Parkinson’s disease: a hypothesis. Journal of Parkinson's disease. 2019;9(s2):S281-S295.
8. Horsager J, Knudsen K, Sommerauer M. Clinical and imaging evidence of brain-first and body-first Parkinson's disease. Neurobiology of disease. 2022;164:105626.
9. Horsager J, Andersen KB, Knudsen K, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020;
10. Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH. Is alpha‐synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Movement Disorders. 2012;27(6):716-719.
11. Chen S-J, Lin C-H. Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis. Journal of Biomedical Science. 2022/07/27 2022;29(1):54. doi:10.1186/s12929-022-00839-6
12. Skjærbæk C, Knudsen K, Horsager J, Borghammer P. Gastrointestinal Dysfunction in Parkinson's Disease. J Clin Med. Jan 31 2021;10(3)doi:10.3390/jcm10030493
13. Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell. 2016;167(6):1469-1480. e12.
14. Cirstea MS, Yu AC, Golz E, et al. Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson's Disease. Movement Disorders. 2020;
15. Lin C-H, Chen C-C, Chiang H-L, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. Journal of neuroinflammation. 2019;16(1):1-9.
16. Hill‐Burns EM, Debelius JW, Morton JT, et al. Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome. Movement Disorders. 2017;32(5):739-749.
17. Wallen ZD, Demirkan A, Twa G, et al. Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Nature Communications. 2022/11/15 2022;13(1):6958. doi:10.1038/s41467-022-34667-x
18. Toh TS, Chong CW, Lim S-Y, et al. Gut microbiome in Parkinson's disease: New insights from meta-analysis. Parkinsonism & Related Disorders. 2022;94:1-9.
19. Baldini F, Hertel J, Sandt E, et al. Parkinson's disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC biology. 2020;18(1):62-62. doi:10.1186/s12915-020-00775-7
20. Adams-Carr KL, Bestwick JP, Shribman S, Lees A, Schrag A, Noyce AJ. Constipation preceding Parkinson's disease: a systematic review and meta-analysis. Journal of Neurology, Neurosurgery & Psychiatry. 2016;87(7):710-716. doi:10.1136/jnnp-2015-311680
21. Villumsen M, Aznar S, Pakkenberg B, Jess T, Brudek T. Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977–2014. Gut. 2019;68(1):18-24.
22. Fu P, Gao M, Yung KKL. Association of intestinal disorders with Parkinson’s disease and Alzheimer’s disease: A systematic review and meta-analysis. ACS Chemical Neuroscience. 2019;11(3):395-405.
23. Liu B, Sjölander A, Pedersen NL, et al. Irritable bowel syndrome and Parkinson’s disease risk: register-based studies. npj Parkinson's Disease. 2021;7(1):1-7.
24. Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register–based matched-cohort study. Neurology. 2017;88(21):1996-2002.
25. Dutta SK, Verma S, Jain V, et al. Parkinson’s disease: the emerging role of gut dysbiosis, antibiotics, probiotics, and fecal microbiota transplantation. Journal of neurogastroenterology and motility. 2019;25(3):363.
26. Parkinson J. An essay on the shaking palsy. The Journal of neuropsychiatry and clinical neurosciences. 2002;14(2):223-236.
27. Pang SY-Y, Ho PW-L, Liu H-F, et al. The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease. Translational Neurodegeneration. 2019/08/16 2019;8(1):23. doi:10.1186/s40035-019-0165-9
28. Paul KC, Ritz B. Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson’s disease. Environment international. 2022;170:107613.
29. Darweesh SK, Vermeulen R, Bloem BR, Peters S. Exposure to Pesticides Predicts Prodromal Feature of Parkinson's Disease: Public Health Implications. 2022;
30. Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3-s8. doi:10.3233/jpd-181474
31. Puigbò P, Leino LI, Rainio MJ, Saikkonen K, Saloniemi I, Helander M. Does Glyphosate Affect the Human Microbiota? Life. 2022;12(5):707.
32. Ruuskanen S, Fuchs B, Nissinen R, et al. Ecosystem consequences of herbicides: the role of microbiome. Trends in Ecology & Evolution. 2023;38(1):35-43. doi:10.1016/j.tree.2022.09.009
33. Caballero M, Amiri S, Denney JT, Monsivais P, Hystad P, Amram O. Estimated residential exposure to agricultural chemicals and premature mortality by Parkinson’s disease in Washington state. International journal of environmental research and public health. 2018;15(12):2885.
34. Chen H-Q, Gong J-Y, Xing K, Liu M-Z, Ren H, Luo J-Q. Pharmacomicrobiomics: Exploiting the Drug-Microbiota Interactions in Antihypertensive Treatment. Review. Frontiers in Medicine. 2022-January-19 2022;8 doi:10.3389/fmed.2021.742394
35. Konstantinidis T, Tsigalou C, Karvelas A, Stavropoulou E, Voidarou C, Bezirtzoglou E. Effects of antibiotics upon the gut microbiome: a review of the literature. Biomedicines. 2020;8(11):502.
36. Ternák G, Németh M, Rozanovic M, Márovics G, Bogár L. Antibiotic Consumption Patterns in European Countries Are Associated with the Prevalence of Parkinson’s Disease; the Possible Augmenting Role of the Narrow-Spectrum Penicillin. Antibiotics. 2022;11(9):1145.
37. Mertsalmi TH, Pekkonen E, Scheperjans F. Antibiotic exposure and risk of Parkinson's disease in Finland: A nationwide case‐control study. Movement Disorders. 2020;35(3):431-442.
38. Pal G, Bennett L, Roy J, et al. Antibiotic exposure and risk of Parkinson's disease in the United Kingdom: A case-control study (P5-11.001). Neurology. 2023;100(17 Supplement 2):0077. doi:10.1212/wnl.0000000000201752
39. Liang X, Bushman FD, FitzGerald GA. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proceedings of the National Academy of Sciences. August 18, 2015 2015;112(33):10479-10484. doi:10.1073/pnas.1501305112
40. Montagner A, Korecka A, Polizzi A, et al. Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Scientific Reports. 2016;6:20127. doi:10.1038/srep20127
41. Leone V, Gibbons SM, Martinez K, et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell host & microbe. 2015;17(5):681-689.
42. Dompe C, Moncrieff L, Matys J, et al. Photobiomodulation-Underlying Mechanism and Clinical Applications. J Clin Med. Jun 3 2020;9(6)doi:10.3390/jcm9061724
43. Glass GE. Photobiomodulation: the clinical applications of low-level light therapy. Aesthetic Surgery Journal. 2021;41(6):723-738.
44. González-Muñoz A, Cuevas-Cervera M, Pérez-Montilla JJ, et al. Efficacy of Photobiomodulation Therapy in the Treatment of Pain and Inflammation: A Literature Review. Healthcare. 2023;11(7):938.
45. Naeser MA, Martin PI, Ho MD, et al. Transcranial Photobiomodulation Treatment: Significant Improvements in Four Ex-Football Players with Possible Chronic Traumatic Encephalopathy. Journal of Alzheimer's Disease Reports. 2023;7:77-105. doi:10.3233/ADR-220022
46. Figueiro Longo MG, Tan CO, Chan S-t, et al. Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury: A Randomized Clinical Trial. JAMA Network Open. 2020;3(9):e2017337-e2017337. doi:10.1001/jamanetworkopen.2020.17337
47. Naeser MA, Martin PI, Ho MD, et al. Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury. Photomed Laser Surg. Dec 2016;34(12):610-626. doi:10.1089/pho.2015.4037
48. Naeser MA, Ho MD, Martin PI, Hamblin MR, Koo B-B. Increased functional connectivity within intrinsic neural networks in chronic stroke following treatment with red/near-infrared transcranial photobiomodulation: case series with improved naming in aphasia. Photobiomodulation, Photomedicine, and Laser Surgery. 2020;38(2):115-131.
49. Stephan W, Banas LJ, Hamblin MR. Treatment Efficacy of Photobiomodulation for Moderate and Advanced Dementia or Alzheimer’s Disease: Case Studies. Advances in Alzheimer's Disease. 2022;11(4):39-47.
50. Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L. Significant improvement in cognition in mild to moderately severe dementia cases treated with transcranial plus intranasal photobiomodulation: case series report. Photomedicine and laser surgery. 2017;35(8):432-441.
51. Herkes G, McGee C, Liebert A, et al. A novel transcranial photobiomodulation device to address motor signs of Parkinson’s disease: a parallel randomised feasibility study. EClinicalMedicine. 2023;66
52. Liebert A, Bicknell B, Laakso E-L, et al. Remote Photobiomodulation Treatment for the Clinical Signs of Parkinson's Disease: A Case Series Conducted During COVID-19. Photobiomodulation, photomedicine, and laser surgery. 2022;40(2):112-122.
53. Liebert A, Bicknell B, Laakso E-L, et al. Improvements in the clinical signs of Parkinson’s disease using photobiomodulation: a 3-year follow-up case series. Medical Research Archives. 2023;11(3)
54. Liebert A, Bicknell B, Laakso EL, et al. Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study. BMC Neurology. 2021/07/02 2021;21(1):256. doi:10.1186/s12883-021-02248-y
55. Shaw VE, Spana S, Ashkan K, et al. Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment. Journal of Comparative Neurology. 2010;518(1):25-40.
56. Peoples C, Spana S, Ashkan K, et al. Photobiomodulation enhances nigral dopaminergic cell survival in a chronic MPTP mouse model of Parkinson’s disease. Parkinsonism & related disorders. 2012;18(5):469-476.
57. Moro C, Torres N, El Massri N, et al. Photobiomodulation preserves behaviour and midbrain dopaminergic cells from MPTP toxicity: evidence from two mouse strains. BMC neuroscience. 2013;14(1):1-9.
58. Reinhart F, El Massri N, Johnstone DM, et al. Near-infrared light (670 nm) reduces MPTP-induced parkinsonism within a broad therapeutic time window. Experimental brain research. 2016;234(7):1787-1794.
59. Gordon LC, Martin KL, Torres N, et al. Remote photobiomodulation targeted at the abdomen or legs provides effective neuroprotection against parkinsonian MPTP insult. European Journal of Neuroscience. 2023;57(9):1611-1624.
60. Johnstone D, El Massri N, Moro C, et al. Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism–an abscopal neuroprotective effect. Neuroscience. 2014;274:93-101.
61. Kim B, Mitrofanis J, Stone J, Johnstone DM. Remote tissue conditioning is neuroprotective against MPTP insult in mice. IBRO Reports. 2018;4:14-17.
62. Bicknell B, Liebert A, Johnstone D, Kiat H. Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases. Lasers in medical science. 2018;34(2):317-327.
63. Salehpour F, Sadigh-Eteghad s, Mahmoudi J, Kamari F, Cassano P, Hamblin M. Photobiomodulation Therapy for Parkinson’s Disease. Photobiomodulation for the Brain Photobiomodulation Therapy in Neurology andNeuropsychiatry. Springer; 2023:chap 10. Synthesis Lectures on Biomedical Engineering.
64. Bicknell B, Liebert A, McLachlan CS, Kiat H. Microbiome Changes in Humans with Parkinson’s Disease after Photobiomodulation Therapy: A Retrospective Study. Journal of Personalized Medicine. 2022;12(1):49.
65. Bicknell B, Laakso E-L, Liebert A, Kiat H. Modifying the microbiome as a potential mechanism of photobiomodulation: A case report. Photobiomodulation, photomedicine, and laser surgery. 2022;40(2):88-97.
66. Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nature Biotechnology. 2019/08/01 2019;37(8):852-857. doi:10.1038/s41587-019-0209-9
67. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Molecular biology and evolution. 2013;30(4):772-780.
68. Price MN, Dehal PS, Arkin AP. FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments. PLOS ONE. 2010;5(3):e9490. doi:10.1371/journal.pone.0009490
69. Bokulich NA, Kaehler BD, Rideout JR, et al. Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2’s q2-feature-classifier plugin. Microbiome. 2018/05/17 2018;6(1):90. doi:10.1186/s40168-018-0470-z
70. McDonald D, Price MN, Goodrich J, et al. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. The ISME Journal. 2012/03/01 2012;6(3):610-618. doi:10.1038/ismej.2011.139
71. Bokulich NA, Dillon MR, Zhang Y, et al. q2-longitudinal: Longitudinal and Paired-Sample Analyses of Microbiome Data. mSystems. 2018;3(6):e00219-18. doi:10.1128/mSystems.00219-18
72. Wallen ZD, Appah M, Dean MN, et al. Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. npj Parkinson's Disease. 2020/06/12 2020;6(1):11. doi:10.1038/s41531-020-0112-6