Parkinson’s disease (PD) involves progressive neurodegeneration with clinical or subclinical disturbance of the gut–brain axis, including altered gastrointestinal motility and enteric nervous system involvement. Clinical studies have reported gut microbiome alterations in PD, with shifts in taxa associated with inflammatory signalling and short-chain fatty acid (SCFA) metabolism. Photobiomodulation (PBM), a non-invasive light therapy, has been investigated as a potential adjunctive treatment for PD, with proposed effects on neural, metabolic, and immune pathways. We previously reported the five-year clinical outcomes in a PBM-treated Parkinson’s disease case series. Here we report the five-year gut microbiome outcomes based on longitudinal samples collected from the same participants. This was an exploratory, open-label longitudinal study without a control group.

Objective: Our objective was to assess whether long-term PBM was associated with changes in gut microbiome diversity and composition in the same Parkinson’s disease cohort as previously assessed for changes in Parkinson’s symptoms.

Methods: Six participants from the earlier PBM proof-of-concept study who had been diagnosed with idiopathic PD and who had continued treatment (transcranial light emitting diode [LED] plus abdominal and neck laser) for five years had their faecal samples analysed by 16S rDNA sequencing to assess microbiome diversity and taxonomic composition.

Results: Microbiome analysis revealed significantly reduced evenness (α-diversity) and significant shifts in β-diversity over five years, as assessed by Permutational Multivariate Analysis of Variance (PERMANOVA). At the phylum level, Pseudomonadota and Methanobacteriota decreased in four of the six participants. Both of these phyla are often increased in the Parkinson’s microbiome compared with the microbiomes of healthy controls. Family-level changes included increased acetate-producing Bifidobacteriaceae (five of the six participants); decreased pro-inflammatory, lipopolysaccharide (LPS)-producing Enterobacteriaceae (two of the three participants who have this bacterial family present); and decreased LPS- and H₂S-producing Desulfovibrionaceae (five of six). At the genus level, Faecalibacterium, a key butyrate producer, increased in four of the six participants, potentially leading to more SCFA availability, although other SCFA-producing bacteria were decreased. This was accompanied by reductions in pro-inflammatory LPS and H₂S-producing genera that are often increased in the Parkinson’s microbiome.

Conclusions: This five-year case series represents the longest follow-up of microbiome changes in Parkinson’s disease, although the interpretation of results is limited by very small numbers, the lack of a control group, and the inability to control for lifestyle influences such as dietary changes. While causal relationships cannot be inferred, the parallel changes in improvements in mobility and non-motor Parkinson’s symptoms observed in this cohort, raises the hypothesis that PBM may interact with the gut–brain axis via the microbiome. Controlled studies incorporating functional multi-omics are needed to clarify potential mechanistic links between microbial function, host metabolism, and clinical outcomes.

Background

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.

Objective

To assess long-term effectiveness of photobiomodulation therapy in a cohort of Parkinson’s disease individuals after five years of continuing therapy.

Methods

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.

Results

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.

Conclusions

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.