The intestinal origin of Parkinson’s disease is beginning to be confirmed. This hypothesis, stated by the German doctor Heiko Braak in 2003proposed that this neurodegenerative disease could be caused by an unknown pathogen which would pass from the digestive tract to the brain through the vagus nerve (which connects the brain and the digestive system).
Already in 2017, Swedish researchers had reinforced this hypothesis by showing that people who had undergone the surgical removal of this nerve had a lower risk of developing the disease, proving the involvement of this intestine-brain connection at least in part of the Parkinson’s case. Also, it is known that digestive problems (such as constipation or inflammation) are linked to this disease and appear years (even decades) before the diagnosis of the disease. A new study, published on November 15, 2023 in the journal Nature Communications, adds a new argument to support Herr Braak’s hypothesis: there would be a significant imbalance in the intestinal microbiota of people with this disease, with an overabundance of pathogenic bacteria.
The microbiota of people with Parkinson’s would cause more inflammation
Researchers at the University of Alabama in the United States observed this intestinal dysregulation by comparing the microbiota of 490 people with Parkinson’s disease with those of 230 “healthy” people (a little more than half of whom were spouses of sick people and therefore shared the same environment).
The intestinal origin of Parkinson’s disease is beginning to be confirmed. This hypothesis, stated by the German doctor Heiko Braak in 2003proposed that this neurodegenerative disease could be caused by an unknown pathogen which would pass from the digestive tract to the brain through the vagus nerve (which connects the brain and the digestive system).
Already in 2017, Swedish researchers had reinforced this hypothesis by showing that people who had undergone the surgical removal of this nerve had a lower risk of developing the disease, proving the involvement of this intestine-brain connection at least in part of the Parkinson’s case. Also, it is known that digestive problems (such as constipation or inflammation) are linked to this disease and appear years (even decades) before the diagnosis of the disease. A new study, published on November 15, 2023 in the journal Nature Communications, adds a new argument to support Herr Braak’s hypothesis: there would be a significant imbalance in the intestinal microbiota of people with this disease, with an overabundance of pathogenic bacteria.
The microbiota of people with Parkinson’s would cause more inflammation
Researchers at the University of Alabama in the United States observed this intestinal dysregulation by comparing the microbiota of 490 people with Parkinson’s disease with those of 230 “healthy” people (a little more than half of whom were spouses of sick people and therefore shared the same environment). Unsurprisingly, the cases of constipation were much more numerous in the cohort of people with Parkinson’s (six times more frequent than for the control group). At the microbiota level, there were clear differences between the two groups, with 55 species of bacteria enriched in the group with Parkinson’s. This was the case, for example, of Bifidobacterium teeth et Actinomyces oris (7 times more abundant) or even Streptococcus mutans (6 times). Among these 55 overabundant species, 11 were bacteria containing on their surface lipopolysaccharides, toxic molecules that activate an immune reaction and cause the release of pro-inflammatory cytokines in the body.
Other species were on the contrary reduced in sick people, such as Roseburia intestinalis (7 times less present) and Blautia vexlera (5 times less). In total, a third of the species normally present in the intestinal microbiota showed abnormal abundances in the group of people with Parkinson’s disease. Among these less abundant species in patients, there were bacteria whose role is to degrade dietary fiber, which could explain the high frequency of constipation in this group (because the fermentation of these fibers by the microbiota promotes intestinal functioning ). According to the authors, this microbiota imbalance highlighted an enrichment of opportunistic pathogens that could lead to more inflammation in the digestive system.
These bacteria weaken the intestinal barrier
The researchers also studied all the genes expressed by the bacteria in the microbiota of the two groups. One of the main findings of this analysis is that the genes necessary for the use of complex carbohydrates (such as starch) were less expressed in people with the neurodegenerative disease. In contrast, those used to degrade proteins and amino acids were more expressed.
This means that the microbiota of people with Parkinson’s prefers to burn proteins rather than sugars for energy. Knowing that these proteins can be those provided by food, but also those already present in the intestines, such as mucins. These proteins line and protect the mucous membranes, including the intestines. It is therefore possible that the imbalance of the microbiota observed in people with Parkinson’s leads to a degradation of these mucins and thus a weakening of the intestinal barrier. This could then favor a possible overflow towards the vagus nerve and then the brain of pathogens or proteins at the origin of this neurodegenerative disease.
The imbalance of the microbiota would directly affect the production of dopamine
Other genes abnormally expressed in the microbiota of patients concerned the synthesis of several neurotransmitters, such as glutamate, serotonin… and dopamine. This latter protein is reduced in Parkinson’s disease due to the loss of the neurons that produce it. But this reduction could also be linked to this imbalanced microbiota. Because the researchers observed that the genes expressed by this microbiota of the patients increased the use of the amino acid tyrosine, necessary for the production of dopamine.
In parallel, the genes necessary for the synthesis of aromatic amino acids, essential also for the production of dopamine, were less expressed. There would therefore be a potential shortage of the building blocks of this neurotransmitter. The involvement of the microbiota in the onset of the disease is not however proven by this study, because the imbalance observed could be a consequence of the disease. However, the results of this research suggest that this imbalance may indeed occur before illness, as it may explain some of the early symptoms mentioned previously, such as constipation and inflammation of the digestive system.
