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MICROBIOTA USAGE TO DIAGNOSE AND TREAT DEMENTIA WITH LEWY BODIES

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 On March 21st, 2023, a research team from the Nagoya University Graduate School of Medicine,in Japan, discovered three gut bacteria types that may lead to predicting and treating dementia with Lewy bodies, that is, Collinsela, Ruminococcus torques, and Bifidobacterium.




WHAT ARE LEWY BODIES?


Lewy body dementia (LBD) is a disease associated with abnormal deposits of a protein called alpha-synuclein in the brain. These deposits, called Lewy bodies, affect chemicals in the brain whose changes, in turn, can lead to problems with thinking, movement, behavior, and mood.

LBD affects more than 1 million individuals in the United States. People typically show symptoms at age 50 or older, although sometimes younger people have LBD. LBD appears to affect slightly more men than women.

A common form of dementia, DLB is characterized by significant cognitive decline, impaired movement, confusion, autonomic dysfunctions, and visual hallucinations. The disease is primarily attributed to the formation of Lewy bodies, which are abnormal clusters of alpha-synuclein protein fibrils that disrupt signal propagation between brain cells.  

Lewy bodies are associated with various neurodegenerative diseases, including Parkinson’s (PD) and idiopathic rapid eye movement sleep behavior disorder (iRBD).

Since DLB and PD dementia maintains similar cognitive profiles, pathologists must look for alternative means of distinguishing between them. Moreover, as many patients develop neurodegenerative diseases in tandem, physicians hope to predict which patients will establish neurological comorbidities and treat them proactively. 


DIAGNOSING AND TREATING NEURODEGENERATIVE DISEASES (SUCH AS DEMENTIA)


The team included iRBD in the study as more than 90% of these patients develop DLB, PD, or PDD within 10 or more years. The sample size was also compared to 147 control patient profiles showing no neurological dysfunction. 

Using a series of differential abundance, statistical, correlation, and permutational multivariate analyses, the team examined each group's taxonomic differences and overall gut microbiota composition across 18 genera and five families

Compared to one another, DLB displayed a significant increase in Ruminococcus torques, Bifidobacterium, and Collinsella over PD and a higher concentration of Collinsella over PDD. Ruminococcus torques and Collinsella increase gut permeability, giving pesticides and herbicides from the diet access to underlying gut neurons to cause inflammation, oxidative stress, and LB formation.  

When the team quantified the fecal bile acids for each diagnostic group, they discovered that the high Ruminococcus torques and Collinsella associated with DLB also increased ursodeoxycholic acid (UDCA), a microbe-produced secondary bile acid. UDCA decreases inflammation in the substantia nigra, a portion of the brain that controls movement. The team believes this may explain why BLD patients experience some symptoms later than those with PD, thereby providing another differentiating factor. 




PD AND DLB TREATMENT OPTIONS


If certain diseases demonstrate a substantial decrease in bacterial concentrations over others, the NUSM team proposed that administering microbes to restore equilibrium may be a therapeutic option. For example, PD patients show a decrease in Collinsella and Ruminococcus torques concentrations compared to other groups. Therefore, increasing those microbes back to a healthy baseline—as opposed to the abnormally high concentration seen in DLB—may be beneficial. “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,” said Ohno. 

The team also observed increased Bifidobacterium in PD patients but quickly determined that PD drugs—catechol-o-methyl-transferase (COMT) inhibitors—caused the increase. Interestingly, patients with PDD demonstrated significantly lower Bifidobacterium concentrations than PD patients, even when both parties were prescribed the same PD drugs. DLB patients also displayed a similar decrease in Bifidobacterium, indicating that this phenomenon may only occur in dementia cases. 

“Our findings can be used for both diagnosis and treatment,” added Ohno. “The presence of intestinal bacteria unique to DLB may explain why some patients develop Parkinson’s disease, and others develop DLB first. 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.” 

The team acknowledges that with just 28 patients, the sample size for DLB warrants more studies with a larger pool. They also aim to conduct a longitudinal study to determine if the associated microbes are causing DLB or if their changes in concentration are merely symptoms. Moving forward, the team seeks to hone their diagnostic skills and design a more exacting therapeutic strategy to predict and treat alpha-synucleinopathies based on an individual’s cognitive and mIcrobiotic profiles.





Comments

  1. Diwakar8 April 2023 at 09:09

    This comment has been removed by the author.

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  2. Diwakar8 April 2023 at 09:41

    Gut health is very essential for healthy functioning body. Very detailed blog.

    ReplyDelete

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