Thomas Sharpton, Ph.D.
Oregon State University
Epigenetic changes in the brain combined with alterations in the gut microbiome may contribute to Alzheimer’s disease (AD), reported NIEHS grantees. Epigenetic changes turn genes on or off without altering the underlying sequence of DNA. This is the one of the first papers to lay the groundwork for linking brain epigenetics and the gut microbiome.
Researchers explored how different genetic mutations interacted to affect behavior and cognitive function related to AD using two different mouse models of the disease and normal mice. The first model contained two mutations in the human amyloid precursor protein (hAPP), found in human populations, and the second added a third hAPP mutation. APP gene mutations generate protein fragments that accumulate in the brain, called amyloid plaques, and are characteristic of AD.
AD-relevant behaviors and cognitive performance were related to hAPP mutations, gender, and the diversity and composition of the gut microbiome. Microbes in the Lachnospiraceae and Ruminococcaceae families were the most commonly involved in interactions between hAPP mutations and behavior.
In a subset of female mice, the team observed different epigenetic changes related to hAPP mutations and gut microbial makeup. For example, female mice with increased epigenetic changes in a gene known to be involved in AD susceptibility also had greater number of gut microbes in the Lachnospiraceae family.
According to the authors, the microbiome may affect AD-related behaviors and cognitive performance via epigenetic changes in AD-susceptibility genes. However, they were unable to rule out that changes in the epigenome may alter conditions that affect the growth of certain taxa in the gut microbiome.
Citation: Kundu P, Torres ERS, Stagaman K, Kasschau K, Okhovat M, Holden S, Ward S, Nevonen KA, Davis BA, Saito T, Saido TC, Carbone L, Sharpton TJ, Raber J. 2021. Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice. Sci Rep 11(1):4678.