2022 Alzheimer's Association Research Fellowship (AARF)

Sex Dependent Effects of Gut Microbiota Manipulation in Alzheimer's disease

How do the gut microbiomes of males and females differentially contribute to Alzheimer’s risk?

Harpreet Kaur, Ph.D.
The Jackson Laboratory
Bar Harbor, ME - United States

Background

The gut microbiome is the community of microorganisms that live within the intestine and impact overall human health. Research suggests that imbalances in the microbiome may be associated with several diseases, including brain diseases. These imbalances could lead to inflammatory changes in the gut and the brain, and have been associated with brain changes in Alzheimer’s. Additionally, recent studies have suggested that males and females have different bacteria in their gut. These sex-specific differences in the gut microbiome may be a part of the larger puzzle to what may be sex differences in Alzheimer’s risk and biological underpinnings. More research is needed to understand connections between gut bacteria and brain function.

Research Plan

Dr. Harpreet Kaur and colleagues previously demonstrated feeding probiotics (live microorganisms that are beneficial to health) to genetically engineered Alzheimer’s-like mice improved memory and decreased brain changes associated with Alzheimer’s. However, this was only in young females and not in older females or males. Based on these findings, the researchers will study if and how the sex and age differences in response to probiotic treatment are impacted by sex hormones regulated by the gut microbiome.

To do this, Dr. Kaur and colleagues will transfer the microbiome of young, female mice treated with probiotics to older female mice and male mice using what’s known as a fecal microbiota transplant. Following the transplants, the researchers will measure changes in performance on tests of memory and anxiety and will measure biological markers of Alzheimer’s and immune response. Finally, the researchers will conduct biological analyses on mouse brain and intestinal tissue to determine how the gut bacteria changes in response to probiotic feeding and transplant.

Impact

The results of the study may provide further insight into the link between the brain and the gut microbiome, and how these biological underpinnings may contribute to Alzheimer’s.  The findings may also further advance our understanding of sex differences in Alzheimer’s.