Five-Year Follow-Up of Photobiomodulation in Parkinson’s Disease: A Case Series Exploring Clinical Stability and Microbiome Modulation

<b>Background</b>: 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. <b>Objective</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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, <i>Faecalibacterium</i>, 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. <b>Conclusions</b>: 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.