A new study reveals a link between gut bacteria and Parkinson’s disease (PD). Researchers have discovered a decrease in genes responsible for the synthesis of essential B vitamins in PD patients, which can weaken the intestinal barrier and lead to inflammation in the brain. This finding suggests that vitamin B supplementation may be a potential therapeutic avenue for PD.
Parkinson’s disease (PD) is a long-term disorder that affects the brain and gradually worsens over time. It causes not only physical symptoms but also affects other parts of the body and mind.
The main physical symptoms are muscle stiffness, difficulty with balance, slowness of movement, trouble walking, and tremors, especially at rest. Non-physical symptoms can include memory problems, depression, reduced sense of smell, bladder problems, constipation, and low blood pressure.
Scientists believe that Parkinson’s is caused by an abnormal buildup of a protein called alpha-synuclein in brain cells that produce dopamine, a chemical that helps control movement and mood.
These clumps, called Lewy bodies, are not confined to the brain but can spread to other areas of the nervous system and even beyond, affecting the sense of smell, the digestive system, and other organs.
In 2003, German neuropathologist Heiko Braak proposed that these harmful protein clumps may start forming in the gut or parts of the brain connected to the gut and then gradually spread to other areas of the brain responsible for movement.
This may explain why some people experience symptoms such as constipation, depression, or certain sleep disorders many years before they develop the common physical symptoms of Parkinson’s. Interestingly, surgery that removes part of a nerve connected to the gut (a vagotomy) appears to reduce the risk of Parkinson’s by about 50 percent, suggesting that the disease may start in the gut for some people.
The role of gut bacteria, or the microbiome, in Parkinson’s is receiving increasing attention. In several studies, researchers have found that people with Parkinson’s tend to have more of certain types of gut bacteria and less of others that are beneficial to overall health.
For example, bacteria like Akkermansia, which breaks down mucus, are often found in larger quantities, while beneficial bacteria like Faecalibacterium and Roseburia are smaller.
Akkermansia bacteria
These bacteria produce essential health substances, such as short-chain fatty acids (SCFAs), which help protect brain cells and support a healthy immune response.
Reduced levels of these SCFAs and certain vitamins produced by gut bacteria, such as B2 (riboflavin) and B7 (biotin), are seen in Parkinson’s and may be involved in its progression.
A study, led by researchers at Nagoya University in Japan, analyzed samples from people with Parkinson’s in several countries. They found that specific bacteria involved in the production of riboflavin and biotin were lower in people with Parkinson’s.
These vitamins are essential because riboflavin, for example, reduces cell damage and inflammation, which are problems in Parkinson’s disease. When gut bacteria do not produce enough of these vitamins, supplementing with riboflavin may be beneficial in helping to protect brain health.
The research also highlights how the gut can become more permeable, allowing harmful substances such as pesticides and other toxins to enter the body and potentially trigger the buildup of harmful proteins in the intestinal nerves.
This research suggests that by improving gut health and restoring balance in gut bacteria, it may be possible to slow or even prevent the progression of Parkinson’s.
Summary and speculative perspectives of the current study. Decreased short-chain fatty acids (SCFAs) and polyamines lead to thinning of mucus layers, which increases intestinal permeability. Increased intestinal permeability may expose the intestinal nerve plexus to pesticides, herbicides, and other toxins, and lead to abnormal aggregation of α-synuclein fibrils. In addition, SCFAs and polyamines facilitate M2 macrophage polarization and relatively decrease M150 macrophage, and their deficiency induces neuroinflammation. Therefore, we hypothesize that intestinal dysbiosis in PD causes decreased fecal production of SCFAs and polyamines, which increases intestinal α-synuclein fibril formation and neuroinflammation. F.p., Faecalibacterium prausnitzii; B.o., Blautia obeum; B.w., Blautia wexlerae; P.v., Phocaeicola vulgatus; B.ov., Bacteroides ovatus; P.d., Phocaeicola dorei; and B.f., Bacteroides fragilis.
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Meta-analysis of shotgun sequencing of gut microbiota in Parkinson’s disease.
Hiroshi Nishiwaki, Jun Ueyama, Mikako Ito, Tomonari Hamaguchi, Keiichi Takimoto, Tetsuya Maeda, Kenichi Kashihara, Yoshio Tsuboi, Hiroshi Mori, Ken Kurokawa, Masahisa Katsuno, Masaaki Hirayama & Kinji Ohno
Nature. npj Parkinsons Dis. 10, 106 (2024).
Abstract:
We aimed to identify gut microbial features in Parkinson’s disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls in Japan with five previously reported datasets from the USA, Germany, China1, China2, and Taiwan. GC-MS and LC-MS/MS assays were established to quantify fecal short-chain fatty acids (SCFAs) and fecal polyamines, respectively. α-Diversity was increased in PD across six datasets. Taxonomic analysis showed that the species Akkermansia muciniphila was increased in PD, while the species Roseburia intestinalis and Faecalibacterium prausnitzii were decreased in PD. Pathway analysis showed that genes in the biosyntheses of riboflavin and biotin were markedly decreased in PD after adjusting for confounding factors. Five out of six categories in carbohydrate-active enzymes (CAZymes) were decreased in PD. Metabolomic analysis of our fecal samples revealed that fecal SCFAs and polyamines were significantly decreased in PD. Genes in the riboflavin and biotin biosyntheses were positively correlated with the fecal concentrations of SCFAs and polyamines. Bacteria that accounted for the decreased riboflavin biosynthesis in Japan, the USA, and Germany were different from those in China1, China2, and Taiwan. Similarly, different bacteria accounted for decreased biotin biosynthesis in the two country groups. We postulate that decreased SCFAs and polyamines reduce the intestinal mucus layer, which subsequently facilitates the formation of abnormal α-synuclein fibrils in the intestinal neural plexus in PD, and also causes neuroinflammation in PD.
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