OHSU-led research in mice expands understanding of the critical role of microbes in the body
New research on mice was published today in the journal Scientific Reports It strengthens the growing scientific consensus regarding the role of the gut microbiome in neurodegenerative disorders including Alzheimer’s disease.
The study, led by researchers at the University of Oregon Health and Sciences, found an association between gut microbiome composition and the behavioral and cognitive performance of mice carrying genes associated with Alzheimer’s disease. Mice carried a human amyloid protein gene with dominant mutations of Alzheimer’s disease bred by scientists in Japan.
The study also indicates a relationship between microbes in the digestive system and the expression of genes that cause Alzheimer’s-like symptoms in mice.
Lead author Jacob Rapper, Ph.D., professor of behavioral neuroscience at OHSU Medical School, said: “You know the expression, ‘You are what you eat? “That could be part of that. While all mice were fed the same diet, the gut microbiome was affected in a genotype-dependent manner, which in turn could affect your brain.
The results are the first to demonstrate a direct link between the gut microbiome and cognitive and behavioral changes in an animal model of Alzheimer’s disease, and are consistent with a recently published observational study of people newly diagnosed with Alzheimer’s disease. In fact, a clinical trial is currently underway in the United States to treat mild to moderate Alzheimer’s disease, using a compound that targets microbes in the gut.
The research published today breaks new ground.
In addition to the measured cognitive and behavioral changes, the study is the first to demonstrate the relationship between changes in the gut microbiome and epigenetic changes in nerve tissue in the hippocampus, an area of the brain affected by Alzheimer’s disease. This type of research is not possible in people.
The microbiome is a complex collection of microorganisms such as bacteria that play an important role in a wide range of functions in the body. In this case, the researchers wanted to see if the gut microbiome affected cognitive and behavioral actions in specially bred mice at 6 months of age. So they compared wild-type mice to those genetically modified to carry the human amyloid gene with predominant Alzheimer’s mutations.
They found changes in the gut microbiome – measured in stool globules – that are consistent with the epigenetic regulation of the lipoprotein E and Tomm40 genes, both of which are associated with Alzheimer’s disease. They found a clear association, but were still unable to determine if one was causing the other.
“Microbes may influence behavioral and cognitive measures related to Alzheimer’s disease through epigenetic changes in the hippocampus,” said Rapper. Or, alternatively, the epigenetic changes in the hippocampus may affect changes in the gut microbiome.
The next stage of the research will determine whether it is possible to reduce Alzheimer’s-like symptoms in genetically predisposed mice by changing their diet.
“The exciting part of this is you can manipulate the gut microbiome,” said Rapper. “We can use probiotics and see the effect.”
Co-authors from Rapper’s Laboratory included postdoctoral fellow Bale Condo, Ph.D., former graduate student Ellen Roth S. Torres, PhD, and Sarah Holden. Rapper collaborated on the research with Thomas Sharpton, Ph.D., an Oregon State University scientist specializing in microbiome studies, and Lucia Carbon, Ph.D., an OHSU scientist who directs the Epigenetics Consortium at the Knight Heart and Vascular Institute, and members of Labs.
The Alzheimer’s disease mutant mice were produced by Takashi Saito, PhD, and Takumi Saido, PhD, from Nagoya City University and the Raken Center for Integrative Medical Sciences, respectively, in Japan.
This research was supported by the National Institutes of Health, awards R56AG057495-01, RF1AG059088, R01ES030226, R21AG065914, T32AG055378, and T32ES007060.
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