Gut Bacteria and Alzheimer’s Disease: Bad Bacteria Could Speed Up the Progression

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The gut microbiome influences the brain and immune system, possibly playing a role in the development and progression of Alzheimer’s disease.

 

 

The community of bacteria living in our gastrointestinal tracts  - the gut microbiome – plays a fundamental role in the development of our immune system and helps protect the body against invading pathogens. Consequently, these bacteria can influence a wide range of diseases, even in distant organs such as the brain. 

 

Recently, disturbances in the gut microbiome community have been linked to diseases including cancer, diabetes and Parkinson’s.

 

Now, in a study published in the Journal of Experimental Disease, scientists have begun to uncover how the gut microbiome affects the development and progression of Alzheimer’s disease.

 

Dementia affects 50 million people worldwide and Alzheimer’s disease is one of the most common forms of dementia; it is characterized by memory loss, confusion and additional cognitive symptoms that gradually progress into almost complete dependence and immobility.

 

Unfortunately, there is no cure. Drugs can relieve some of the symptoms but not stop the progression of the disease.

 

We don’t understand exactly how Alzheimer’s causes these neurological symptoms. The disease is partially characterized by a buildup of protein clumps in the brain, called amyloid-beta plaques, which appear alongside the cognitive decline. Although amyloid beta accumulation characterizes the disease, much remains unknown about where these plaques come from and how they wreak so much havoc in the brain.

 

The Gut Microbiome Could Speed Up the Progression of Alzheimer’s Disease

The microbes in the gastrointestinal tract influence the immune system and the brain, possibly playing a role in the development of Alzheimer’s

 

Dementia affects 50 million people worldwide. Alzheimer’s disease is one of the most common forms of dementia; it is characterized by memory loss, confusion and other cognitive symptoms that gradually progress into near-total dependence and immobility. About one-third of people that live until age 90 will develop a form of dementia. There is no cure. Drugs can ameliorate some symptoms but cannot stop the progression of the disease.

 

For unknown reasons, women are more likely to develop Alzheimer’s disease than men.

 

Although we don’t understand exactly how Alzheimer’s causes these symptoms, the disease is partially characterized by a buildup of protein clumps in the brain, called amyloid-beta plaques, which appear along with cognitive decline. Though amyloid beta accumulation characterizes the disease, much remains unknown about how these plaques wreak so much havoc in the brain.

 

Normally, the immune system removes amyloid-beta plaques, but scientists think the immune system may also accelerate Alzheimer’s progression. 

 

When the immune cells in the brain (called microglia) encounter amyloid-beta plaques, they become proinflammatory and release inflammatory chemicals that at high concentrations, may actually make Alzheimer’s worse.

 

Thus, Dodiya and colleagues sought to understand the role of the microbiome in the development of Alzheimer’s and why women are more likely to develop the disease than men.

 

The research team tested the effects of the gut microbiome on amyloid beta and microglia in the brain using a line of transgenic mice that produce extra amyloid precursor proteins.

 

First, the researchers treated the mice with antibiotics to alter their gut microbial communities. 

 

When they looked at brain tissue from the mice, they found that their microglia were behaving properly and the mice had fewer amyloid beta plaques than non-antibiotic-treated mice. 

 

To confirm that the change in microbial communities contributes to these effects, the researchers then reintroduced microbes by transplanting fecal matter from healthy mice back into another mice that had been treated with antibiotics. 

 

Reintroducing the microbes partially restored the amyloid beta plaques and increased the expression of markers for inflammation-causing microglia. 

 

Notably, although the researchers tested both male and female mice, they only found these changes in male mice.

 

This is not the first study comparing how the microbiome has different effects in different sexes, but it highlights the importance of considering sex when thinking about treatments for Alzheimer’s and other diseases.

 

The finding that antibiotics reduce Alzheimer’s symptoms in male mice can now be used to better understand the timing and influence of gut bacteria on Alzheimer’s disease.  Hopefully, further studies will help to extend these finding to humans.

 

Reference

Dodiya et al. (2019). Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes. JEM. DOI: 10.1084/jem.20182386