Dementia with Lewy bodies (DLB) is a common form of dementia that currently has no cure. Previous research has suggested that the gut microbiome, or the microorganisms that reside in the human digestive tract, may play a role in the neurodegenerative disease of Parkinson’s disease. However, the specific bacteria involved in DLB have not yet been identified.
Now, a group led by researchers from the Graduate School of Medicine at Nagoya University in Japan has identified three bacteria implicated in DLB: Collinsella, Ruminococcus, And Bifidobacterium. Their findings, reported in the journal npj Parkinson’s diseasesuggest new avenues for diagnosis and treatment.
The appearance of DLB is associated with abnormal deposits of alpha-synuclein, a brain protein that plays a role in transmitting signals between neurons. The presence of these deposits, known as “Lewy bodies”, affects chemicals in the brain, leading to impaired thinking, reasoning and memory. Symptoms include confusion, memory loss, impaired movement, and visual hallucinations.
Parkinson’s disease also begins with movement problems, but some patients develop cognitive decline within a year. These patients are diagnosed with DLB when this cognitive decline occurs. Doctors struggle to predict which people with Parkinson’s disease will develop cognitive decline within a year and become patients with DLB.
A research group led by Associate Professor Masaaki Hirayama (omics medicine), Professor Kinji Ohno (neurogenetics) and Assistant Professor Hiroshi Nishiwaki (neurogenetics) from
They discovered that three intestinal bacteria, Collinsella, Ruminococcus, And Bifidobacterium, were associated with patients with DLB. This may suggest possible avenues for diagnosis and treatment of this neurodegenerative disease.
The researchers also found similarities between gut bacteria implicated in Parkinson’s disease and DLB. In both diseases, the bacteria Akkermansia, which degrades the intestinal mucosa, increased. On the other hand, bacteria that produce short-chain fatty acids (SCFAs) in the intestine have decreased. “Decreases in SCFA-producing bacteria have been repeatedly reported in Parkinson’s disease,
Likewise, both Ruminococcus Couples And Collinselle are gut bacteria that carry an enzyme whose product regulates inflammation in a region of the brain called the substantia nigra. The substantia nigra produces dopamine, a neurotransmitter involved in movement regulation and deficient in Parkinson’s disease. Compared to Parkinson’s disease, levels of these bacteria were higher in people with DLB. This may explain why the effect on movement is delayed, a key feature that distinguishes DLB from Parkinson’s disease.
“Our results can be used for both diagnosis and treatment,” says Ohno. “If a patient with Parkinson’s disease develops dementia one year after the onset of motor symptoms, they are diagnosed with DLB. However, we cannot currently predict whether a patient with Parkinson’s disease will become a DLB patient. The gut microbiome will help identify these patients.
“In terms of treatment, the administration of Ruminococcus Couples And Collinselle in patients with Parkinson’s disease should delay neuroinflammation in the substantia nigra,” Ohno added. “Therapeutic intervention to increase Bifidobacterium may delay the onset and progression of DLB and reduce cognitive dysfunction.
“The presence of gut bacteria unique to DLB may explain why some patients develop Parkinson’s disease and others develop DLB first,” Ohno said. “Normalizing the abnormal bacteria shared between DLB and Parkinson’s disease may delay the development of both diseases. Improving the gut microbiota is a stepping stone in the treatment of dementia. Our discoveries could pave the way for the discovery of new and completely different therapies.
Reference: “Gut microbiota in dementia with Lewy bodies” by Hiroshi Nishiwaki, Jun Ueyama, Kenichi Kashihara, Mikako Ito, Tomonari Hamaguchi, Tetsuya Maeda, Yoshio Tsuboi, Masahisa Katsuno, Masaaki Hirayama and Kinji Ohno, December 9, 2022, npj Parkinson’s disease.