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.

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.

Parkinson’s disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson’s disease and their care givers. Parkinson’s disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome–gut–brain axis is also important in Parkinson’s disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson’s disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson’s disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson’s disease and may potentially slow its progression.

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.

Objective: The objective of this case study was to elucidate the effect of photobiomodulation (PBM) on the microbiome. Background: The gut microbiome has been identified as a key component of health, with gut dysbiosis, characterized by decreased microbial diversity and an altered microbial composition, being recognized as instrumental in many diseases and disorders. Previous research has suggested that the gut microbiome can be favorably altered in animal models using PBM. Materials and methods: The participant had their microbiome tested on nine occasions, three times before any treatment, three times after radiotherapy and commencement of immunotherapy for breast cancer, and three times after PBM treatment. The PBM treatment consisted of infrared laser treatment (904 nm; 700 Hz pulse frequency, 861.3 total joules) to the abdomen three times per week for 11 weeks. Results: The microbiome of the participant showed significant changes in diversity after PBM treatment, but not after cancer therapy, with an increase in the number of known beneficial bacteria (Akkermansia, Faecalibacterium, and Roseburia) and decrease in the number of potentially pathogenic genera. Conclusions: The results suggested the possibility that PBM may alter the microbiome and thus it represents a therapeutic avenue for chronic diseases with otherwise limited treatment options.

Parkinson’s disease is a progressive neurodegenerative disease characterized by clinical motor signs and non-motor symptoms that severely impact quality of life. There is an urgent need for therapies that might slow, halt or even reverse the progression of existing symptoms or delay the onset of new symptoms. Photobiomodulation is a therapy that has shown potential to alleviate some symptoms of Parkinson’s disease in animal studies and in small clinical trials. To assess long-term effectiveness of photobiomodulation therapy in a cohort of Parkinson’s disease individuals after five years of continuing therapy. Eight participants of the initial 12 in a previously published study agreed to be reassessed after five years. Seven of these participants had continued home-based, self-applied photobiomodulation therapy three times per week for five years. One participant had discontinued treatment after one year. Participants were assessed for a range of clinical motor signs, including MDS-UPDRS-III, measures of mobility and balance. Cognition was assessed objectively, and quality of life and sleep quality were assessed using self-reported questionnaires. A Wilcoxon Signed Ranks test was used to evaluate change in outcome measures between baseline (before treatment) and after five years, with the alpha value set to 0.05. Of the seven participants who had continued photobiomodulation therapy, one had a preliminary diagnosis of multisystem atrophy and was excluded from the group analysis. For the remaining six participants, there was a significant improvement in walk speed, stride length, timed up-and-go tests, tests of dynamic balance, and cognition compared to baseline and nonsignificant improvements in all other measures, apart from MDS-UPDRS-III, which was unchanged and one measure of static balance (single leg stance, standing on the unaffected leg with eyes open) which declined. Five of six participants either improved or showed no decline in MDS-UPDRS-III score and most participants showed improvement or no decline in all other outcome measures. No adverse effects of the photobiomodulation therapy were reported. This study provides a signal that photobiomodulation therapy might safely reduce important clinical motor signs and non-motor symptoms in some Parkinson’s disease patients, with improvements maintained over several years. Home-based photobiomodulation therapy has the potential to complement standard therapies to manage symptoms and potentially delay Parkinson’s symptom progression. Australian New Zealand Clinical Trials Registry, registration number ACTRN12618000038291p, registered on 12/01/2018.