Gut Microbiome Dysbiosis: Can Light Therapy (PBMT) Help?

The gut microbiome's critical role in human health is increasingly recognized, with imbalances (dysbiosis) linked to diverse diseases. This clinical trial report explores photobiomodulation therapy (PBMT), a non-invasive approach utilizing red and near-infrared light, as a potential modulator of gut microbiota. Emerging evidence suggests PBMT can beneficially influence the gut microbiome composition, promoting beneficial bacteria, reducing inflammation, and impacting Vitamin D levels. Supporting animal studies and theoretical frameworks point to PBMT's promise in addressing gut-related disorders, including neurological conditions like Alzheimer's and Parkinson's. While highlighting PBMT's potential as a supportive therapy, this report underscores the need for further research to optimize its application.

The article explores the gut microbiome's critical role in health, emphasizing the balance between beneficial and harmful bacteria. It defines dysbiosis as an imbalance linked to various diseases and introduces Photobiomodulation Therapy (PBMT), using red (630-700 nm) and near-infrared light (700-1200 nm), as a potential modulator of the gut microbiome, particularly for dysbiosis-related disorders.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10835098/#sec2

doi:  10.22037/ghfbb.v16i4.2687

The gut microbiome, containing approximately 10^14 bacterial cells (10 times more than human cells), significantly influences health. Dysbiosis is associated with conditions like IBD and type 2 diabetes. Light, influencing circadian rhythms, can affect the gut microbiota. PBMT has shown promise in stimulating healing and reducing inflammation. For example, Bicknell et al. found that PBMT (808 nm NIR light, three times a week for 12 weeks) increased Allobaculum by 10,000-fold in healthy mice. Chen et al. showed that PBMT at 630 nm and 730 nm decreased Helicobacter pylori and uncultured Bacteroidales while increasing Rikenella in a mouse model for Alzheimer's disease. Continuous light exposure increased Bacteroidales S24-7, while continuous dark exposure increased Bacteroidales and Rikenellaceae. A study showed a ten-fold abundance of epithelial-associated commensal bacteria in the dark phase.

The gut microbiome, a focus of projects like HMP and MetaHIT, consists of commensal and pathogenic microorganisms. Dysbiosis, an imbalance in the gut microbiome, leads to reduced beneficial bacteria and increased harmful ones. The dominant bacterial phyla are Firmicutes (approximately 64%) and Bacteroidetes (approximately 23%), constituting about 90% of the gut microbiota. In a healthy state, the gut microbiome produces beneficial metabolites (SCFAs) with anti-inflammatory properties. SCFAs (acetate, propionate, and butyrate) regulate intestinal epithelial cell function and reduce inflammation. Conversely, Gram-negative bacterial lipopolysaccharides (LPS) induce pro-inflammatory cytokines (IL-6, MIP-3α, TNF-α), disrupting the gut barrier and leading to inflammation. The gut microbiome modulates macrophages, influencing inflammatory responses and maintaining intestinal homeostasis, which is essential for preventing inflammatory disorders.

Dysbiosis plays a proven role in intestinal inflammation, linked to both Crohn’s disease (CD) and ulcerative colitis (UC), which are types of IBD. Studies indicate that patients with IBD exhibit alterations in the diversity and composition of their intestinal microbiota. Dysbiosis and changes in gut microbial metabolites in IBD patients can lead to intestinal macrophage activation, an increased Th2/Th1 ratio, and stimulated IL-22 production, ultimately resulting in intestinal inflammation.

IBS is a gastrointestinal disorder with complex causes. Evidence suggests that dysbiosis triggers the activation of the gut's innate immune responses, increased expression of toll-like receptors (e.g., TLR4) by macrophages, and enhanced production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α). Furthermore, in IBS patients, the adaptive immune response shows an imbalance in Th1/Th2 regulation and an increase in pro-inflammatory cytokines. Changes in the gut microbiome composition observed in IBS patients include an increase in Lactobacillus, Veillonella, and Enterobacteriaceae, alongside a decrease in Bifidobacterium and Clostridium compared to healthy individuals.

Celiac disease (CeD) is an autoimmune enteropathy triggered by immune responses to undigested gliadin peptides. Dysbiosis contributes to CeD by disrupting the intestinal barrier, allowing gliadin peptides to enter the lamina propria and trigger an immune response. Gram-negative bacteria (Bacteroidetes, Proteobacteria, Verrucomicrobia, and Fusobacteria) produce LPS, activating TLR4-related inflammation and damaging the intestinal barrier. Conversely, Gram-positive bacteria like Lactobacilli and Bifidobacterium, considered probiotics, enhance cell-binding protein expression to control inflammation. Studies indicate that Lactobacilli and Bifidobacterium species are decreased in CeD patients compared to control groups.

Several hypotheses link the gut microbiome to brain function. Gut microbiota metabolomes (SCFAs, gamma-aminobutyric acid, noradrenaline, acetylcholine, dopamine, and serotonin) have neuroactive properties. The gut microbiome interacts with the central nervous system (CNS) via the brain-gut-microbiome axis. The microbiome produces LPS, a potential trigger for neuroinflammation, which can contribute to neurological disorders. Research indicates that patients with severe autism, amyotrophic lateral sclerosis, and Alzheimer's disease exhibit higher serum levels of this endotoxin compared to healthy individuals. Dysbiosis can overstimulate innate immune responses through toll-like receptor 4 and activate oxidative stress, potentially triggering Parkinson's disease.

Photobiomodulation therapy was found by Endre Mester in 1967 ( 41 ). PBMT, which is the use of red (630-700 nm) and near-infrared light (700 and 1200 nm), was shown to have the potential to be used as a supportive treatment option for reducing inflammation and accelerating pain and wound healing ( 42 ). In PBMT, photons interpenetrate to the tissue and are absorbed by cytochrome c oxidase in mitochondria and calcium ion channels, which leads to an increase in enzyme activity, oxygen consumption, and ATP production ( 43 ). Additionally, photons have the ability to separate nitric oxide (NO) into an active form from the heme and Cu centers of cytochrome c oxidase ( 44 ). Vasodilation and increased blood flow are two of the most significant physiologic processes in which NO is involved ( 45 ). Furthermore, under normal conditions, photons of PBMT increase reactive oxygen species (ROS) production leading to the activation of several transcription factors, increased gene expression, enhanced protein synthesis, etc. ( 7 ,  44 ). But, under oxidative stress and pathological conditions, PBMT reduces ROS, NO, and NF-kB production, and induces anti-inflammatory effects ( 12 ). PMBT can decrease the production of prostaglandin E2 (PGE2) and pro-inflammatory cytokines, such as IL-1ß, IL-6, IL-8, IL-12 and TNFα ( 32 ). Sousa et al. in 2017 showed that 660 nm PMB could significantly diminish the TNFα, CCL,3 and CXCL2 mRNA expression by activating M1 macrophages 4 hours after irradiation ( 46 ). In another recent study, it was shown that PBM can modulate the ratio of M1 and M2 macrophage phenotypes, suppress a range of macrophage-associated pro-inflammatory cytokines and chemokines, and increase anti-inflammatory cytokines in a time-dependent and wavelength-dependent manner ( 47 ).

The study generated the following results:

• NIR Light (808 nm): Increased Allobaculum abundance by 10,000-fold when applied to the abdomen.
• Light/Dark Exposure: Continuous dark exposure increased Bacteroidales and Rikenellaceae; continuous light exposure increased Bacteroidales S24-7.
• Light Stress: Resulted in a ten-fold abundance of epithelial-associated commensal bacteria in the dark phase.
• Sunlight/UVB: Seasonal variations altered microbiome composition. Decreased UVB exposure and vitamin D deficiency promoted gut dysbiosis.
• PBMT (630 nm & 730 nm): Decreased Helicobacter pylori and uncultured Bacteroidales, while increasing Rikenella. Also improved Alzheimer's symptoms in a mouse model with application to the head and abdomen.
• PBMT (Head, Nose, Neck, Abdomen): Led to positive changes in the Firmicutes to Bacteroidetes ratio and clinical symptom improvement in Parkinson's disease.

PBMT is presented as a promising, non-invasive supportive therapy for gut microbiota-related conditions. Further research is needed to determine optimal dosages and treatment schedules for specific conditions, but the therapy shows high tolerability and few side effects. PBMT can diminish a range of clinical symptoms of Parkinson’s disease and affect the gut microbiome composition, showing positive changes in the Firmicutes to Bacteroidetes (F: B) ratio in these patients.