The secretion of amyloid proteins by our gut flora would lead to the appearance of similar proteins in the brain. Amyloid protein clusters in neurons are involved in neurodegenerative diseases such as Parkinson’s or Alzheimer’s.
Parkinson’s disease, Alzheimer’s disease, cerebral degeneration, amyotrophic lateral sclerosis, all these neurodegenerative diseases have one thing in common: the death of neurons associated with the accumulation of so-called amyloid proteins (different depending on the disease).
Abnormal proteins aggregate into a kind of “balls of yarn” that fill neurons and are then transferred from neuron to neuron between different brain regions, causing inflammation (an immune system response) and cell death. The central question was therefore where these amyloid proteins come from.
Researcher Shu Chen from Case Western Reserve University in Cleveland and his colleagues have shown that they come from our gut, more specifically from bacteria in the gut flora. Until now, we did not know how the first abnormal proteins that fold poorly and accumulate in neurons are formed.
A significant inflammatory response has also been observed around the brain regions where these proteins aggregate, without knowing whether or not it causes neuron death. On the other hand, amyloid proteins were known to already be present in the gut and gut neurons of patients, sometimes 20 years before Parkinson’s disease is diagnosed.
It’s all in the gut
Our intestines contain more than 1.5 kilograms of bacteria. This gut flora or microbiota has many roles in digestion, anti-inflammation, etc. These bacteria are mostly not only harmless but also essential for survival. In 2002 it was discovered that some of them produce amyloid proteins useful for their proliferation, adhesion and resistance.
The “curli” proteins, which are secreted by Escherichia coli bacteria, have been best studied. Chen and his colleagues hypothesized that these gut flora amyloid proteins cause other amyloid proteins to appear in brain neurons.
They decided to study the aggregation of one of these proteins, alpha-synuclein, which accumulates in the neurons of patients suffering from Parkinson’s disease. To do this, they fed 344 aged rats and C. elegans worms (genetically modified to express human alpha-synuclein) with curli-producing Escherichia coli bacteria for two or three months, other animals were given modified bacteria to stop producing curli to produce.
Result: The rats that received E. coli secreting the curli showed aggregated alpha-synuclein proteins in the gut and in the gut neurons, but also in the neurons of the brain. The worms developed clumps of alpha-synuclein proteins in their muscle cells.
Conversely, animals exposed to non-curli-producing bacteria developed very few amyloid aggregates. In addition, the appearance of amyloid proteins elicited an intense local inflammatory response in the rat brain, comparable to that observed in the brains of patients suffering from neurodegenerative diseases.
Gut flora in poor health: worsened inflammation
How do amyloid proteins secreted by bacteria indirectly affect neurons? Scientists put forward three hypotheses. The presence of bacterial aggregate proteins could cause over-expression of alpha-synuclein throughout the organism, which would then favor its aggregation.
Unless the aggregation is transferred to other proteins quasi step-by-step. Or that immune activation generated in the gut by bacterial amyloid proteins leads to an immune response and inflammation in the brain; Inflammation, which would then be the origin of cerebral protein aggregation.
This study is one of the first to show that the microbiota is capable of causing aggregation of abnormal proteins in brain neurons. This is a new research avenue to better understand or even treat neurodegenerative diseases as we now have many tools to study and act on the gut microbiota.
Gut and gut flora health through diet and regular intake of probiotics remains a priority for those who care about their current and future health.
Chen et al., Exposure to the functional bacterial amyloid protein curli enhances alpha-synuclein aggregation in aged Fischer 344 rats and Caenorhabditis elegans, Nature
See also: Vision problems: possibly early signs of Alzheimer’s
* Presse Santé strives to convey health knowledge in a language accessible to all. In NO CASE can the information given replace the advice of a doctor.
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Alzheimer’s amyloid Escherichia coli intestinal flora Parkinson’s