Optimal Health Medical Blog

The Blog of Dr. Henry Sobo

THE GUT MICROBIOME AND DEMENTIA

THE GUT MICROBIOME AND DEMENTIA
The term microbiome refers to our bodies’ natural biologic environment which includes  trillions of organisms, such as bacteria, viruses and fungi  which live inside of all of us. Our gastrointestinal tract has been the subject of extensive research seeking to understand how these organisms affect us, and how we may improve our health and prevent or delay disease with this knowledge. It is known that our gastrointestinal microbiome plays a vital role in maintaining overall health by helping to digest food and make nutrients. There is also an immune supporting role the microbiome plays as well as having a “gut-brain ” connection via the nervous system which affects our brain and neurological functions. An unhealthy state of imbalance of the organisms of the microbiome contributes to disease.
Research has uncovered that the brain and the gut microbiome are connected through a complex network of nervous system cells called neurons , and natural chemicals that relay messages throughout the body and to the brain.
Researchers are trying to further elucidate how this all works and to hopefully uncover  health practices and treatments that may delay brain pathologies like dementia and Alzheimer’s disease.
Our gut microbiome plays a role in brain inflammation

It is felt  that Chronic inflammation in the brain contributes to the development of Alzheimer’s. The mechanism that  Research has suggested is that in response to a variety of challenges, immune cells in the brain called microglia release cytokines which are inflammatory molecules, which draw other immune cells to do the same, causing more inflammation. This may lead to a chronic state of inflammation which then results in damage to other nervous system cells called neurons and death of brain cells.

It is felt that in an aging brain, the  microglia  become more activated and create a stronger immune response which persists over time and contributes to brain degenerative disease such asAlzheimer’s disease.

Research has suggested that mechanisms exist  that connects gut inflammation and brain inflammation. Studies have shown that high-fiber foods, including whole grains, fruits, and vegetables, may help to reduce inflammation in the gut. Some types of gut bacteria use the fiber from these foods to produce short-chain fatty acids (SCFAs), which have anti-inflammatory properties. These have been found to improve memory in animal studies.

Research has been done to study the effects of a diet high in fiber on the brains’ microglia immune cells. What was seen was that in aged mice, a high-fiber diet changed the balance of the different type bacteria in the gut microbiome. It results in increased production of the short chain fatty acids (SCFAs), and reduced  inflammation in the brain. Then in a follow-up study, it was seen that in old mice a high-fiber diet shifted the health of the microglial cells back to a less inflammatory , more normal, state that would be seen in younger adult mice.

These researchers are  Currently trying to determine the mechanism involved in creating the benefits of SCFAs and refine possible treatments that could be applied  Lead researcher R. Johnson, PhD. says ,  “We’re learning more about how diet might be used to change the gut microbiome and support brain health.”

Understanding Age Related Changes in the Gut Microbiome

As we age, the bacteria living in our gut changes. The population of bacteria in our gut becomes less diverse. with fewer different types of bacteria present . As this loss of diversity occurs potentially harmful bacteria are allowed to grow to excess, promoting illness.

Louise D. McCullough, M.D., Ph.D., is  a professor and neurologist at UTHealth Houstn. Her research attempts to see if age-related changes in the gut microbiome can be reversed to slow or prevent neurodegenerative disease. She explains that in her research, “hours after a stroke, the gut barrier becomes leaky. This allows very bad bacteria in the gut to circulate throughout the body and cause serious infections and even death, especially in older mice. Because infections are a common cause of death after stroke, and the risk is higher in older patients, our research may point toward new approaches to help with recovery.” Her research team transplanted a young gut microbiome into old mice and an aged microbiome into young mice. They then caused strokes experimentally and studied the effects on the mice. In the old mice with a newly transplanted young gut microbiome, survival after a stroke increased by more than 50%. And the opposite occurred when young mice had a transplant of an  aged gut microbiome . These mice developed cognitive problems, and more of them died after a stroke. This gives us more evidence that  the aged microbiome contributes to brain toxicity. Their research  also pointed to the beneficial effects of short chain fatty acids (SFCAs), with younger microbiomes producing more, and the aged microbiomes producing less SCFAs. They tested this hypothesis, giving mice a combination of SCFAs and the prebiotic inulin.It seemed to work and the treated mice showed signs that inflammation and neuron damage were mitigated. This lends hope to treatments that may lead to people to be treated similarly to reduce neurological diseases such as Alzheimer’s disease.

The microbiome, Cholesterol and metabolism

The gut microbiome plays a central role in regulating human metabolism. Different types of gut bacteria influence which substances are produced and released into the bloodstream and central nervous system.

Changes in the metabolic processes which involve the metabolism of cholesterol have been associated with Alzheimer’s disease. Rima Kaddurah-Daouk, Ph.D. of  the Duke University School of Medicine, leads the  Alzheimer’s Disease Metabolomics Consortium .His reseacrh attempts to find the  metabolic changes that correlate with the cognitive decline and are associated with Alzheimer’s. He says ,

“Metabolism is the end product of a partnership between a person and their gut bacteria. When that relationship is affected — by diet or age, for example — a person’s metabolism changes, and that can affect the brain.”

He studied cholesterol clearance in 1,474 older adults with cognitive function from normal to late-stage Alzheimer’s disease. He found that “Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific role for the gut-brain axis in neurodegeneration. Bile acids (BA), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer disease (AD).”

Normally the liver breaks down cholesterol into bile acids (BAs), and the gut bacteria convert  what are called the primary BAs to secondary BAs. He found that people with Alzheimer’s disease had lower amounts of liver-produced BAs but higher amounts of bacterially produced secondary BAs in their blood, and that the higher  levels of secondary BAs were  associated with cognitive decline.

Research continues to further elucidate what might be done to successfully alter the course of cognitive decline in the so many millions of sufferers of Alzheimer’s and related conditions

https://www.nia.nih.gov/news/beyond-brain-gut-microbiome-and-alzheimers-disease#inflammation