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Can changes in how microorganisms develop in the gut during childhood promote one’s risk for late-life Alzheimer’s?
Ziad Al Nabhani, Ph.D.
University of Bern
Bern, Switzerland
Background
The gut microbiome is the community of microorganisms that live within the intestine and impact overall human health. Research suggests that the presence of specific, harmful microbes present in the gut microbiome (microbiota) may be associated with several diseases, including brain disorders. These harmful microbes could lead to inflammatory changes in the gut and the brain, and they have been associated with brain changes in Alzheimer’s.
In recent studies with Alzheimer’s-like mice, Dr. Ziad Al Nabhani and colleagues examined how the presence of certain microbes beginning in childhood, at the stage when infants transition from milk to solid food (a stage also known as “weaning”) can affect overall health as the mice age. Weaning leads to an increase in the total amount of gut microbes, and the researchers found that this increase also promotes the development of immune cells called regulatory T cells (or Tregs). Tregs are important in maintaining brain health over an individual’s lifetime. However, weaning that produces an increase in certain harmful microbes may also promote dysfunctional Tregs. This may in turn lead to brain inflammation and Alzheimer’s later in life. Dr. Al Nabhani’s findings suggest important links between the composition of the gut microbiota in childhood and later-life brain disease.
Research Plan
Dr. Al Nabhani and team will now conduct a larger study to clarify these links. First, they will examine Alzheimer’s-like mice that have been engineered to lack various types of gut microbes. During the animals’ weaning period, the mice will be treated with compounds that either promote or inhibit microbiome expression (or the making of microbiome proteins from genes). They will then assess how differences in microbe composition lead to brain changes linked with Alzheimer’s, including losses in memory and nerve cell communication, as well as the formation of beta-amyloid protein plaques (a hallmark brain change in Alzheimer’s). Next, the investigators will look for specific microbiota that are linked to Alzheimer’s progression in the mice, and they will determine how these microbes may impact the development of microglia (the primary immune cells of the brain). Lastly, they will study how weaning-related changes in specific microbes impact Treg levels in the mice, and how abnormal Treg levels may impact brain inflammation and Alzheimer’s.
Impact
Results from this study could shed new light on the role of the gut in brain health. They could also lead to novel therapies for preventing dementia that begin decades before disease symptoms become evident.
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