Targeted Strategies
Parkinson’s disease (PD), a progressive neurodegenerative disorder, is commonly associated with motor symptoms but is often preceded by gastrointestinal issues long before diagnosis. Emerging studies reveal a strong link between gut dysbiosis and PD. These disruptions in the gut microbiome may drive disease progression through mechanisms such as increased intestinal permeability, inflammation, and neurotransmitter imbalances.
Although a distinct microbial pattern has yet to be identified, recurring features such as a decrease in short-chain fatty acid-producing bacteria and an increase in pro-inflammatory microbes suggest that gut health plays an important role in the onset and progression of PD. (See the companion IPA blog Parkinson’s Disease and Gut Microbiota: Part 1 Unraveling the Connection for a detailed exploration into the research regarding PD and the mechanisms of gut microbiome involvement.)
As knowledge of the connection between gut microbiota and PD expands, researchers are investigating therapeutic strategies that may mitigate symptoms and slow PD progression by targeting gut microbes. These include antibiotics, probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation.
The broad range of microbiota modulation remedies being explored reveals both the urgency and hope for alleviating the suffering caused by this devastating disease.
Let’s take a look at each individually.
Antibiotics
Antibiotics: “compounds that target bacteria and, thus, are intended to treat and prevent bacterial infections.”
Antibiotics not only clear pathogenic microbes but certain antibiotics also have neuroprotective effects, including anti-inflammatory, immunomodulatory, and antioxidant actions, and may prevent abnormal protein aggregation. Their repurposing for neurological disorders like PD is promising, as existing safety profiles expedite clinical trial approval.
In addition to many antibiotic agents that have been employed to exert neuroprotective effects or alleviate PD symptoms listed in a recent review, combinations of antibiotics may help correct microbial imbalances, and treatments for Helicobacter pylori and SIBO, both linked to PD, are already established.
While some antibiotics show potential in correcting microbial imbalances, their use requires caution due to risks of dysbiosis, as seen with minocycline, which showed promise for treating PD but failed in clinical trials, highlighting the need for continued research.
Probiotics
Probiotics: “Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”
In light of the strong evidence that probiotics promote intestinal motility, protect the intestinal barrier, support a balanced mucosal immune system, and inhibit harmful microorganisms, researchers have tested their potential in the management of PD.
Animals
In the nematode Caenorhabditis elegans model of synucleinopathy, Bacillus subtilis probiotics inhibited and cleared α-synuclein aggregates via biofilm formation, bacterial metabolites, and changes in cellular lipid composition.
In a mouse PD model, Lactiplantibacillus plantarum delayed neurodegeneration caused by α-synuclein accumulation in the substantia nigra by reducing oxidative stress, suppressing inflammation, and modulating gut microbiota.
A study with a transgenic PD mouse model showed that long-term administration of multi-strain probiotics had neuroprotective effects on dopamine neurons and further attenuated the deterioration of motor dysfunctions.
Hence, the neuroprotective effects of probiotics in PD are evident in studies on animals but as we shall see, limited in humans. However, research on clinical improvements in gut function is more robust.
Humans
In an early study in 2011, researchers first observed that regular consumption of fermented milk containing Lacticaseibacillus casei improved stool consistency and alleviated bloating and abdominal pain in PD patients experiencing constipation.
Since then, many other probiotics have been tested in PD patients with resultant beneficial effects on gastrointestinal symptoms: for example, Lactobacillus acidophilus and Bifidobacterium infantis given together and another study using multi-strain probiotics (L. acidophilus, Limosilactobacillus reuteri, Lactobacillus gasseri, Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecalis, Enterococcus faecium) showed positive results.
Probiotics are also being used in managing Helicobacter pylori infections to restore the balance of commensal bacteria following antibiotic treatment. In PD patients, this may aid in enhancing the absorption of levodopa, a key pharmaceutical treatment that unfortunately loses its effectiveness over time.
Thus, evidence suggests that probiotic consumption can improve non-motor symptoms associated with gastrointestinal dysfunction. In addition, there are some studies regarding their effectiveness in preventing or influencing motor symptoms of PD.
In a 12-week randomized, double-blind, placebo-controlled clinical trial, PD patients who received a probiotic containing L. acidophilus, B. bifidum, L. reuteri, and Limosilactobacillus fermentum showed improved scores on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) compared to the control group. The same study also recorded reductions in oxidative stress biomarkers along with increased levels of glutathione (an antioxidant reduced in PD patients). Reductions in insulin levels and insulin resistance were also observed in the probiotic group.
In another study, Ligilactobacillus salivarius and L. acidophilus significantly reduced pro-inflammatory and increased anti-inflammatory cytokines in PD patients compared to matched controls.
A different study demonstrated that L. plantarum supplementation for 12 weeks improved the MDS-UPDRS motor score in PD patients.
Prebiotics
Prebiotic: “a substrate that is selectively utilized by host microorganisms conferring a health benefit”
Certain dietary fibers and indigestible oligosaccharides qualify as prebiotics because they stimulate the growth of beneficial gut bacteria by being fermented in the colon. This fermentation generates short-chain fatty acids (SCFAs) and lowers gut pH, fostering the growth of beneficial bacteria that contribute to gut health in PD. (Note that prebiotics may also derive from non-fiber substances, such as polyphenols.)
Enhanced SCFA production reduces intestinal permeability, inflammation, and endotoxin crossing among other benefits.
Prebiotics may also boost brain-derived neurotrophic factor (BDNF) levels, reducing neuroinflammation and protecting dopaminergic neurons as observed in a study in rodents.
Prebiotic supplementation and simple dietary changes, like adopting a Mediterranean diet rich in fiber, polyphenols, and omega-3 fatty acids, can help lower the risk of PD and offer neuroprotection. In contrast, the Western diet, low in fiber and high in animal protein and sugars, reduces beneficial SCFA production, increasing PD risk and worsening disease severity.
Although clinical studies linking PD and prebiotics are limited, evidence indicates that prebiotics can improve immune function, gastrointestinal health, and neuroprotection suggesting their potential clinical value. While recent research highlights their promise for various diseases linked to gut dysbiosis, a study found that although all prebiotic fibers stimulated SCFA production, butyrate levels can be improved in PD patients but were still lower compared to healthy individuals, indicating that prebiotics may be most effective as an adjunct to support microbiome health and gastrointestinal function.
Synbiotics
Synbiotic: “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”
A study administering fermented milk with multistrain probiotics and prebiotic fiber found the regimen was superior to placebo in improving constipation in patients with PD.
A recent study demonstrated that a new synbiotic of polymannuronic acid and L. rhamnosus had neuroprotective effects in a PD animal model by increasing tyrosine hydroxylase expression, preventing dopaminergic neuron death, and improving motor function through anti-inflammatory and anti-apoptotic actions of short-chain fatty acids and enhanced neurotrophic factor expression.
Postbiotics
Postbiotics: “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”
Though the definition of postbiotics is disputed, short-chain fatty acids (SCFAs) and other metabolites like bioactive peptides, tryptophan degradation products, bile acids, and vitamins produced by probiotic microbes, are considered postbiotics, which can be supplemented without live bacteria. Recent studies highlight their benefits in reducing inflammation, neurotoxicity, and oxidative stress, with butyrate supplementation showing promise in alleviating motor symptoms, improving dopamine levels, and repairing gut damage in PD animal models, although human research is needed to confirm these effects.
Fecal Microbiota Transplantation
Fecal microbiota transplantation (FMT): transferring stool from a healthy donor to restore the gut microbiome in a patient, with fecal matter delivered through methods such as colonoscopy, nasal-jejunal tube, or orally via capsules.
Animals
In animal models of PD, FMT has been shown to enhance dopamine levels in the substantia nigra (part of the basal ganglia), reduce neuroinflammation, modulate immune responses, lower α-synuclein expression, and alleviate motor symptoms. One study found that mice receiving FMT from PD mice displayed motor dysfunction and lower striatal dopamine and serotonin levels, while those receiving stool from healthy mice exhibited significant recovery in dopamine, serotonin, and motor function, suggesting FMT’s potential to protect dopaminergic neurons.
Humans
Multiple clinical trials reveal promising results for FMT in PD.
One notable study involved 54 participants, with half of the treatment group showing significant improvements in motor and non-motor symptoms, including GI symptoms by week 12 compared to the placebo group. While no significant differences in microbiota diversity were found between responders and non-responders at baseline or week 12, certain microbial species were notably altered in responders and correlated positively with clinical improvements, indicating potential biomarkers for treatment efficacy.
Despite positive outcomes from FMT, the treatment faces challenges, including ethical concerns, donor selection, transplant handling, optimal administration protocols, risk-benefit assessment, and long-term safety.
Takeaway
New research is shedding light on the surprising role of gut health in Parkinson’s disease. Scientists have found that disruptions in the gut microbiome—specifically, a loss of beneficial bacteria and an increase in harmful, inflammatory microbes—may contribute to the disease’s progression. These gut imbalances are thought to affect the brain by increasing intestinal permeability and triggering chronic inflammation. In response, researchers are exploring the use of antibiotics, probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation to target the gut and slow Parkinson’s disease progression. While these approaches show promise, much remains to be understood about their long-term efficacy and safety.
Image by Gerd Altmann from Pixabay
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