Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

A Randomized Placebo-Controlled Study of a Transcranial Photobiomodulation Helmet in Parkinson's Disease: Post-Hoc Analysis of Motor Outcomes.

Emerging evidence is increasingly supporting the use of transcranial photobiomodulation (tPBM) to improve symptoms of neurodegenerative diseases, including Parkinson's disease (PD). The objective of this study was to analyse the safety and efficacy of tPBM for PD motor symptoms. The study was a triple blind, randomized placebo-controlled trial with 40 idiopathic PD patients receiving either active tPBM (635 nm plus 810 nm LEDs) or sham tPBM for 24 min per day (56.88J), six days per week, for 12 weeks. The primary outcome measures were treatment safety and a 37-item MDS-UPDRS-III (motor domain) assessed at baseline and 12 weeks. Individual MDS-UPDRS-III items were clustered into sub-score domains (facial, upper-limb, lower-limb, gait, and tremor). The treatment produced no safety concerns or adverse events, apart from occasional temporary and minor dizziness. There was no significant difference in total MDS-UPDRS-III scores between groups, presumably due to the placebo effect. Additional analyses demonstrated that facial and lower-limb sub-scores significantly improved with active treatment, while gait and lower-limb sub-scores significantly improved with sham treatment. Approximately 70% of participants responded to active treatment (≥5 decrease in MDS-UPDRS-III score) and improved in all sub-scores, while sham responders improved in lower-limb sub-scores only. tPBM appears to be a safe treatment and improved several PD motor symptoms in patients that responded to treatment. tPBM is proving to be increasingly attractive as a possible non-pharmaceutical adjunct therapy.

Remote Photobiomodulation Treatment for the Clinical Signs of Parkinson's Disease: A Case Series Conducted During COVID-19.

Objective: To assess whether remote application of photobiomodulation (PBM) is effective in reducing clinical signs of Parkinson's disease (PD). Background: PD is a progressive neurodegenerative disease for which there is no cure and few treatment options. There is a strong link between the microbiome-gut-brain axis and PD. PBM in animal models can reduce the signs of PD and protect the neurons from damage when applied directly to the head or to remote parts of the body. In a clinical study, PBM has been shown to improve clinical signs of PD for up to 1 year. Methods: Seven participants were treated with PBM to the abdomen and neck three times per week for 12 weeks. Participants were assessed for mobility, balance, cognition, fine motor skill, and sense of smell on enrolment, after 12 weeks of treatment in a clinic and after 33 weeks of home treatment. Results: A number of clinical signs of PD were shown to be improved by remote PBM treatment, including mobility, cognition, dynamic balance, spiral test, and sense of smell. Improvements were individual to the participant. Some improvements were lost for certain participants during at-home treatment, which coincided with a number of enforced coronavirus disease 2019 (COVID-19) pandemic lockdown periods. Conclusions: Remote application of PBM was shown to be an effective treatment for a number of clinical signs of PD, with some being maintained for 45 weeks, despite lockdown restrictions. Improvements in clinical signs were similar to those seen with the application of remote plus transcranial PBM treatment in a previous study. Clinical Trial Registration number: U1111-1205-2035.

Improvements in clinical signs of Parkinson's disease using photobiomodulation: a prospective proof-of-concept study.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. OBJECTIVE: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). METHODS: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. RESULTS: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. CONCLUSIONS: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.

A Potential Role for Photobiomodulation Therapy in Disease Treatment and Prevention in the Era of COVID-19.

COVID-19 is an evolving pandemic that has far reaching global effects, with a combination of factors that makes the virus difficult to contain. The symptoms of infection can be devastating or at the least very debilitating for vulnerable individuals. It is clear that the elderly are at most risk of the adverse impacts of the virus, including hospitalization and death. Others at risk are those with comorbidities such as cardiovascular disease and metabolic conditions and those with a hyper-excitable immune response. Treatment options for those with acute responses to the virus are limited and there is an urgent need for potential strategies that can mitigate these severe effects. One potential avenue for treatment that has not been explored is the microbiome gut/lung axis. In addition to those severely affected by their acute reaction to the virus, there is also a need for treatment options for those that are slow to recover from the effects of the infection and also those who have been adversely affected by the measures put in place to arrest the spread of the virus. One potential treatment option is photobiomodulation (PBM) therapy. PBM has been shown over many years to be a safe, effective, non-invasive and easily deployed adjunctive treatment option for inflammatory conditions, pain, tissue healing and cellular energy. We have also recently demonstrated the effectiveness of PBM to alter the gut microbiome. PBM therapy is worthy of consideration as a potential treatment for those most vulnerable to COVID-19, such as the elderly and those with comorbidities. The treatment may potentially be advantageous for those infected with the virus, those who have a slow recovery from the effects of the virus and those who have been denied their normal exercise/rehabilitation programs due to the isolation restrictions that have been imposed to control the COVID-19 pandemic.