Parkinson’s Could Begin in the Gut and Then Move to The Brain

Highlights

• Scientists found that gastro-intestinal problems that included constipation were present before neurological symptoms were expressed in Parkinson’s patients.
• Study on gut microbes showed that gut microbes influenced motor deficits in mice prone to Parkinson’s.
• Probiotic therapy and antibiotic therapy have been found to aid in lowering motor deficits in mice prone to Parkinson’s.

Researchers have found that gut microbes play a crucial role in Parkinson’s like movement disorder in mice that are genetically compromised. The study published in the Journal Cell found that antibiotic therapy eliminated movement deficits and molecular hallmarks that were found in Parkinson’s like disease in mice. The study findings highlight the influence of gut microbes on Parkinson’s disease, which is the second most common neurodegenerative disease in the U.S.

Dr. Sarkis Mazmanian of the California Institute of Technology who is the senior author of the study spoke about the significance of the study, “We have discovered for the first time a biological link between the gut microbiome and Parkinson's disease. More generally, this research reveals that a neurodegenerative disease may have its origins in the gut, and not only in the brain as had been previously thought. The author further added saying "The discovery that changes in the microbiome may be involved in Parkinson's disease is a paradigm shift and opens entirely new possibilities for treating patients."

Scientists have thus far been studying changes in the brain and possible causative factors in patients with this neurodegenerative disorder, however, this is the first time that gut microbes have been studied with an effect on Parkinson’s disease.

Parkinson’s Disease

Parkinson’s disease is a neurodegenerative disorder.

• This condition was first described in 1817 by James Parkinson, a British physician who called the condition “the shaking palsy”
• It belongs to a group of diseases called movement disorders
• One million people in the U.S are found to be affected by this disease
• India has the lowest incidence of Parkinson’s, 70 in 100,000 people.
• The Parsi community has one of the highest incidences of Parkinson’s with an incidence of 328 in 100,000.
• The condition results in the loss of nerve cells, especially in the region substantia nigra, in the brain.

The most characteristic symptom associated with Parkinson’s is tremors, which is the involuntary movement of the extremities.

Other symptoms include stiffness of the muscles, slow movement and an impairment of the gait.

Gut Microbes as a Possible Source

Lead author Mazmanian, along with Timothy Sampson of the California Institute of Technology studied Parkinson’s in an attempt to identify possible causes for the condition. The starting point of the current research was gastro-intestinal problems like constipation that occurs in patients with Parkinson’s even before the start of motor symptoms. This was due to changes in the gut microbiome of these individuals. Gut microbiomes have been previously studied and have been implicated in autism, anxiety, depression and cognitive ability but this is the first study that examined gut microbes in Parkinson’s disease.

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Effect of Gut Microbes

The researchers grew genetically modified mice (mice that were prone to acquiring a disease similar to Parkinson’s) either in a normal cage which was not sterile or in a cage that was germ free.

• The mice that grew in the germ-free environment showed lower deficits in motor activity and there was less accumulation of misfolded protein present in regions of the brain that were involved in motor ability. Moreover, these mice showed normal activity like removing adhesive from the nose, crossing a beam and going down a pole.
• Antibiotic treatment given to mice which grew in a normal environment resulted in a similar reduction in motor deficits.
• Mice that were grown in cages that were germ-free and which were treated with fecal transplants of gut microbes from mice that were grown in normal environment showed worst motor symptoms.

These results were used to determine that gut microbe had a significant effect on motor ability in mice that were predisposed to Parkinson’s.

Gut Microbes and Genes

The scientists concluded that gut microbes worked along with genes that resulted in Parkinson’s. When mice that were genetically modified to be prone to motor deficits were treated with fecal transplants, there was an exacerbation of the symptoms. While mice that were genetically normal did not show any change on fecal transplants from a patient with Parkinson’s.

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Probiotic Therapy

Probiotic therapy, according to the researchers, will aid in alleviating the symptoms associated with the condition. They also found that fecal transplants and antibiotics might not be viable forms of treatment at this stage.

Dr. Sampson cautioned “Long-term, high-strength antibiotic use, like we utilized in this study, comes with significant risk to humans, such as defects in immune and metabolic function. Gut bacteria provide immense physiological benefit, and we do not yet have the data to know which particular species are problematic or beneficial in Parkinson's disease."

The researchers at this stage are focusing on identifying bacteria that offer protection and isolating bacteria that could trigger motor deficits.

Mazmanian further added that "Much like any other drug discovery process, translating this innovative work from mice to humans will take many years. But this is an important first step toward our long-term goal of leveraging the deep, mechanistic insights that we have uncovered for a gut-brain connection to help ease the medical, economic, and social burden of Parkinson's disease."

Gut microbes are becoming increasingly important. The presence of gut microbes improves our digestive process and their presence was thought to protect the body from attachment by harmful micro-organisms.

However recent advances have shown that gut microbes could increase the risk for rheumatoid arthritis, eye diseases antiphospholipid syndrome and a host of other infections.

Such studies bring to the fore the importance of maintaining ‘good’ gut bacteria by consuming probiotic yogurt on a regular basis.

References:

1. What is Parkinson’s Disease? - (http://www.pdf.org/about_pd)

Source-Medindia