Araştırmacılar, Lewy cisimcikli demans ile ilişkili bağırsak bakterilerini tanımladılar. Kredi bilgileri: Reiko Matsushita
Lewy cisimcikli bunama (DLB), şu anda tedavisi olmayan yaygın bir bunama türüdür. Önceki araştırmalar, bağırsak mikrobiyomunun veya insan sindirim sisteminde bulunan mikroorganizmaların, nörodejeneratif bozukluk Parkinson hastalığında rol oynayabileceğini öne sürdü. Bununla birlikte, DLB’de yer alan spesifik bakteriler henüz tanımlanmamıştır.
Şimdi, Japonya’daki Nagoya Üniversitesi Tıp Fakültesi’ndeki araştırmacılar tarafından yönetilen bir grup, DLB’ye karışan üç bakteri tanımladı: Collinsella, Ruminococcus, Ve bifidobakteri. Bulguları, dergide bildirildi npj Parkinson Hastalığıteşhis ve tedavi için yeni yollar önerir.
DLB’nin başlangıcı, beyinde nöronlar arasında sinyallerin iletilmesinde rol oynayan bir protein olan anormal alfa-sinüklein birikintileri ile ilişkilidir. ‘Lewy cisimcikleri’ olarak bilinen bu birikintilerin varlığı beyindeki kimyasalları etkileyerek düşünme, akıl yürütme ve hafızada düşüşlere yol açar. Semptomlar kafa karışıklığı, hafıza kaybı, bozulmuş hareket ve görsel halüsinasyonları içerir.
Parkinson hastalığı da hareket problemleriyle başlar, ancak bazı hastalarda bir yıl içinde bilişsel gerileme gelişir. Bu bilişsel gerileme meydana geldiğinde bu hastalara DLB teşhisi konur. Doktorlar, Parkinson hastalığı olan hangi kişilerin bir yıl içinde bilişsel gerileme geliştireceğini ve DLB hastası olacağını tahmin etmekte zorlanıyor.
Doçent Masaaki Hirayama (Omics Medicine), Profesör Kinji Ohno (Nörogenetik) ve Yardımcı Doçent Hiroshi Nishiwaki (Nörogenetik) liderliğindeki bir araştırma grubu.[{” attribute=””>Nagoya University Graduate School of Medicine, in collaboration with Okayama Neurology Clinic, Iwate Medical University, and Fukuoka University, analyzed microorganisms in the gut and fecal bile acids of patients with DLB, Parkinson’s disease, and rapid eye movement behavior disorder.
They discovered that three intestinal bacteria, Collinsella, Ruminococcus, and Bifidobacterium, were associated with patients with DLB. This may suggest possible ways of diagnosing and treating this neurodegenerative disease.
The researchers also found similarities between the gut bacteria involved in Parkinson’s disease and DLB. In both diseases, the bacteria Akkermansia, which degrades the intestinal mucosa, increased. On the other hand, the bacteria that produce short-chain fatty acids (SCFA) in the gut decreased. “Decreases in SCFA-producing bacteria have been repeatedly reported in Parkinson’s disease, Alzheimer’s disease, and ALS,” explains Ohno. “This suggests that it is a common feature of neurodegenerative diseases.” SCFA are important because they produce regulatory T cells. These types of cells play a critical role in regulating the immune system by suppressing neuroinflammation.
On the other hand, in patients with DLB, the researchers found an increase in Ruminococcus torques, an increase in Collinsella, and a decrease in Bifidobacterium. This was different from Parkinson’s disease patients, whose levels did not change. In the future using these insights, doctors may be able to analyze the bacteria in a person’s digestive tract to distinguish DLB from Parkinson’s disease.
Importantly, the reduced levels of Bifidobacterium may also suggest possible ways to treat DLB. Bifidobacterium increases brain-derived neurotrophic factor, a key protein that supports the growth, development, and maintenance of neurons in the central and peripheral nervous systems. Therefore, its decrease in DLB is likely to be associated with cognitive decline.
Similarly, both Ruminococcus torques and Collinsella are intestinal bacteria that carry an enzyme, the product of which regulates inflammation in a region of the brain called the substantia nigra. The substantia nigra produces dopamine, a neurotransmitter that is involved in the regulation of movement and is deficient in Parkinson’s disease. Compared to Parkinson’s disease, the 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 findings can be used both for both diagnosis and treatment,” explains Ohno. “If a patient with Parkinson’s disease develops dementia in 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 to identify such patients.”
“In terms of treatment, the administration of Ruminococcus torques and Collinsella in patients with Parkinson’s is expected to 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 intestinal 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 findings may pave the way for the discovery of new and completely different therapeutics.”
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, 9 December 2022, npj Parkinson’s Disease.
DOI: 10.1038/s41531-022-00428-2