Mapranosis: the Influence of Commensal Microbes on Neurodegenerative Disease
Commensal microbes are the largely helpful populations that live inside us, usually meaning the gut microbiota, but there are others, such as the bacteria found in the mouth. Among these largely helpful microbes are a range of species that cause us harm over the years, however - consider the bacterial origins of gum disease, for example. Researchers are increasingly interested in the ways in which the swarming microbial life inside us, and particularly in the gut, might influence the progression of aging; to what degree are gut bacteria a cause of the observed natural variations in pace and outcome of aging in mammals? This is an open question.
In the case of neurodegenerative conditions such as Alzheimer's disease, microbial life may contribute by generating some fraction of the amyloid deposits or chronic inflammation known to be associated with the condition. In this context, some scientists are focused on invading microbes such as spirochetes, while others, like those noted here, are more interested in the commensal microbes that normally live inside us. There is a fair amount of evidence for either of these two classes of microbe to be involved.
Research in the past two decades has revealed that microbial organisms in the gut influence health and disease in many ways, particularly related to immune function, metabolism, and resistance to infection. Recent studies have shown that gut microbes also may cause or worsen Parkinson's disease, Alzheimer's disease and other neurodegenerative conditions. Researchers now propose the term "mapranosis" for the process by which amyloid proteins produced by microbes (bacteria, fungi and others) alter the structure of proteins (proteopathy) and enhance inflammation in the nervous system, thereby initiating or augmenting brain disease. The term is derived from Microbiota Associated Protepathy And Neuroinflammation + osis (a process).
Research into the multitude of microbes that inhabit the human body has expanded considerably in recent years. Genomic analysis has begun to reveal the full diversity of bacteria, viruses, fungi, archaea, and parasites living in and on the body, the majority of them in the gut. Even more recently, researchers have begun to explore how the proteins and other metabolites produced by microbes inhabiting the gut influence functions in other parts of the body, including the brain. However, we do not yet have a full understanding of how these systems work. The relationship between the microbiota and the brain has been called the "gut-brain axis."
It is understood that the clumping of misfolded amyloid proteins, structures produced by neurons in the brain, are associated with neurodegeneration and conditions such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). "It is well known that patterns of amyloid misfolding of neuronal proteins are involved in age-related brain diseases. Recent studies suggest that similar protein structures produced by gut bacteria, referred to as bacterial amyloid, may be involved in the initiation of neurodegenerative processes in the brain. Bacterial amyloids are produced by a wide range of microbes that inhabit the GI tract, including the mouth. Our work suggests that our commensal microbial partners make functional extracellular amyloid proteins, which interact with host proteins through cross-seeding of amyloid misfolding and trigger neuroinflammation in the brain."