Gut Microbiome May Have Central Role in Alzheimer’s and Like Diseases, Study Argues

The gut microbiome is increasingly seen as a key player in serious and chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s — for reasons that are being suggested and explained, but not quite named.

Now, researchers propose a term — “mapranosis” — to capture the process by which amyloid proteins produced by certain gut microbes can modify the structure of amyloid proteins in the brain produced by neurons, leading to inflammation in the central nervous system.

By giving it a name researchers hope to increase awareness of the gut-brain axis among clinicians and researchers alike, and spur greater investigation into it.

“It is critical to define the ways in which gut bacteria and other organisms interact with the host to create disease, as there are many ways in which the microbiota may be altered to influence health,” Robert P. Friedland, M.D, the study’s lead author and a neurology professor at the University of Louisville, said in a press release.

The term — proposed by Friedland and Matthew Chapman, a professor at the University of Michigan — defines the damage caused to proteins and the inflammation that follows by the natural community of microorganisms that reside in our gut. This community,  the so-called gut microbiome, is a diverse population of different bacteria, viruses, fungi, archaea and parasites.

Certain members of the gut microbiome produce amyloid proteins similar to those produced by neurons. These microbiome-produced proteins have the capacity to alter the structure of the other proteins, increasing the inflammation associated with neurodegeneration.

“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,” Friedland said. “Bacterial amyloids are produced by a wide range of microbes that inhabit the GI tract, including the mouth.”

In a 2016 study called “Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans,” published in the journal Scientific Reports, Friedland and colleagues showed that E.coli, a bacteria present in the gut, produces amyloid proteins with an abnormal configuration, meaning they are misfolded.

Using rats and worms (nematodes), the researchers observed that when E.coli produced these abnormal proteins, then the animals’ own amyloid proteins also became abnormal — a process called cross-seeding.

“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,” Friedland said.

In a new study, “The role of microbial amyloid in neurodegeneration” published in the journal PLOS Pathogens, Friedland and Chapman introduce “mapranosis” and discuss in greater detail studies into how and why the gut microbiome modulates the risk and progression of neurodegenerative disorders like Alzheimer’s and Parkinson’s.

They highlight complex interplay between the human host and its resident microbiota, and discuss how the gut microbiome modulates the body’s immune response — including that of the central nervous system.

For example, some evidence points to the products of gut bacteria metabolism playing a dual role: one that’s either protective or damaging. This itself could be a factor of where one lives. “Cultural differences in human populations can also have a profound influence on the microbiota,” the researchers write. In fact, the geographical region where a person lives can influence the composition of the gut microbiota and, consequently, neurodegeneration.

“The role that intestinal microbes play during Alzheimer disease, Parkinson disease, and related disorders is a particularly dynamic pursuit because the composition and diversity of the microbiota are so variable in the human population,” the team notes.

Exploring the gut-brain axis, and its intricate and delicate interactions, may lead to therapies for neurodegenerative diseases that now have few effective ones available, the team concludes.