Study performed in rats and nematodes show that the gut microbes produce toxic amyloid proteins that are similar to those characteristic of neurodegenerative diseases. The studies suggest that it is possible that the amyloid proteins produced by gut microbes may trigger the process of neurodegeneration.
Neurodegenerative diseases are diseases that are caused by the damage to neurons. Most of these diseases are detected only in the later stages and since the exact manifestation of the diseases remains only partially known, the area lacks effective treatment. Alzheimer’s disease (AD) is the most common neurodegenerative disease, followed by Parkinson’s disease (PD) in the order of incidence. Amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Batten disease are other known neurodegenerative diseases. Intensive and extensive research in the field of neurodegenerative diseases reveals that while some diseases are caused due to genetic mutations, others are caused by the accumulation of toxic proteins in the cells and yet others are caused due to gradual cell death is commonly known as apoptosis or programmed cell death.
Recent research suggests that most of the neurodegenerative diseases are connected to each other at some level at the sub-cellular level. For example, AD, PD, and ALS are characterized by the presence of amyloid proteins that are toxic to the nerve cells. The amyloid proteins are not to be confused with the amyloid precursor protein (APP) which is an essential protein for the growth of nerve cells. It has been speculated that by some mechanism the APP is chipped off to smaller fragments called amyloid proteins that are seen in these neurodegenerative diseases. Alpha-synuclein is another such protein that is present at the synapses of nerves and greatly enables nerve functions. In neurodegenerative diseases especially Alzheimer’s it has been observed that alpha-synuclein forms aggregates or clumps also called amyloid proteins that are toxic to the brain.
Suggested role of gut microbes in neurodegenerative diseases
A recent study at the University Of Louisville School Of Medicine conducted by Robert P. Friedland and his team attempted to understand the cause of clumping and misfolded proteins that lead to inflammation in the brain and are characteristic of neurodegenerative diseases. The research performed by them suggests that the microbes in our gut could be responsible in the triggering of the processes that result in the production of these toxic misfolded proteins. Their study reveals that gut microbes produce amyloid proteins that are structurally similar to the misfolded proteins in the brain; these amyloid proteins produced by the microbes trigger the immune system and cause greater inflammation in the brain. It has also been suggested that the presence of these amyloid proteins in the gut leads to increased clumping of protein alpha-synuclein in the brain.
The study was carried out in rats by feeding them with bacterial strains of Escherichia coli that produce bacterial amyloid protein curli. E. coli are microbes that are normally present in the natural gut microflora. Control animals were maintained by administering bacteria that could not produce the amyloid protein. The rats fed with curli protein producing organisms exhibited greater levels of aggregation of alpha-synuclein proteins in the intestine and brain as is characteristic of neurodegenerative diseases. They also exhibited enhanced cerebral inflammation.
Similar studies were collaboratively performed at Case Western Reserve University by neuroscientist Shu G. Chen in nematode Caenorhabditis elegans that were fed with curli producing E. coli and showed similar results as observed in rats.
These new developments give researchers a greater insight into the nature and possible sources of neurodegeneration and will help them develop suitable therapies for the treatment and prevention of neurodegenerative diseases at an earlier stage.