Most of the intestinal microorganisms influence neuronal development, behaviour, and contribute to various neurological disorders. A new finding by scientists in the United States revealed that pathological changes in the microbes of intestine represent a risk for the onset of pathogenesis of Parkinson’s disease (PD).
Most of the neurological disorders like Alzheimer’s, Huntington’s, and Parkinson’s diseases (PD) are characterized by abnormal accumulation of specific neuronal proteins and often lead to behavioural, psychiatric, and neurodegenerative changes. PD is one such multifactorial disorder that arises from alpha-synuclein (aSyn) protein accumulation and exhibits intestinal inflammation, and gastrointestinal (GI) and motor abnormalities. Generally, permanent colonization of microbes in the GI tract has a profound effect and control over the differentiation and function of immune cells in the intestine, periphery, and brain. Therefore, research studies have been carried out to learn how changes in the gut microbiome have an impact on overall health and the risk of the onset of various diseases like obesity, cancer, as well as conditions that affect the brain, including autism, anxiety, and depression. The findings of a new study on the functional link between gut microorganisms and PD was published in the journal Cell in 2016.
The study was carried out by Mazmanian and colleagues in the United States, in genetically modified mice for understanding the crucial role of gut microorganisms on the onset of PD. In the study, some of the mice were bred in a fully sterile environment, thereby causing them to lack gut microbes while the remaining mice, which were exposed to a normal environment, had an abundance of microbes in the intestine. The research team exposed these groups of mice to running on a treadmill and crossing a beam and tested their motor skills. It was observed that the germ-free mice performed much better than the mice with gut microbes. In addition, examination of the expression of the protein alpha-synuclein (aSyn) in genetically modified rodents with Parkinson’s disease (PD) has revealed characteristic accumulation of the aSyn protein along with motor symptoms. Therefore, findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD. The researchers also transplanted the gut microbes isolated from the fecal samples of either healthy individuals or adults suffering from Parkinson’s disease into the mice who were germ-free. Remarkably, fecal microbes from PD patients were observed to impair motor function in transplanted mice much more than microbes obtained from healthy people. Together, these results suggest that gut microbes may play a critical and functional role in the pathogenesis of synucleinopathies such as PD. In addition, the study also revealed germ-free mice with Parkinson’s symptoms showed more levels of short-chain fatty acids (SCFAs) in their feces indicating brain inflammation, nerve cell damage, and death.
In summary, Parkinson’s disease may not only be impacted by etiology in the brain but also by microbes in the gut. Therefore, microbes of the intestine play a key role in the motor and GI function of PD by neuroinflammation and aSyn aggregation. In addition, the link between gut bacteria and anxiety, depression, and autism indicates neurological disorders are not only associated with pathological changes in the brain but also may also have etiologies in the gut.
Written By: Manche Santoshi, PhD