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Tracking COVID-19 at UCLA

UCLA researchers investigate relationship between gut microorganisms, brain

Mice that ate diets low in carbohydrates and were subjected to reduced oxygen levels had an altered gut bacteria makeup, which may have contributed to lower scores on cognitive tests, according to a new UCLA study. (Sakshi Joglekar/Assistant Photo editor)

By Elyssa Smith

Aug. 28, 2021 2:36 p.m.

UCLA researchers found an association between cognitive impairment and an altered gut microbiome in mice, furthering scientific understanding of the brain-gut connection.

The study published Aug. 5 looked at how environmental factors, such as diet, can increase risk for impaired cognition. Its findings added to a growing body of research investigating the role of the microbiome in overall health.

The researchers altered the mice’s microbiome, consisting of microbes and bacteria that are in and on the body, by using a diet low in carbohydrates and reducing their levels of oxygen. These conditions led to increased levels of a bacteria called Bilophila wadsworthia, which affected the learning and memory center of the brain and was associated with worse performance by mice on memory tasks, according to the study.

B. wadsworthia increased the number of cells in the body that are responsible for helping facilitate the body’s immune response, and eliminating these cells led to improved performance on memory tasks, according to the study.

Geoff Pronovost, a doctoral student in molecular biology and a co-author of the study, said the gut microbiome consists of different bacteria that reside within the gut and can nearly be thought of as its own living organ.

These bacteria thrive off of the nutrients consumed, so diet is critical for regulating the composition of the microbiota, Pronovost added.

Pronovost said the research team chose to study the low-carbohydrate, high-fat ketogenic diet because of its known association with changes in an organism’s brain and behavior. For example, the ketogenic diet has been used to treat seizures for those who are not responsive to anti-seizure medication, he added.

To test cognition in mice, researchers used a circular maze filled with holes and one designated target hole for the mice to recall, said Grace Yang, a fourth-year human biology and society student and a co-author of the study.

Yang said the mice were trained to go through the target hole before being subjected to the stressors, reduced oxygen levels and a ketogenic diet. Researchers measured how well mice with varying microbiomes were able to perform on the maze task.

Christine Olson, the lead author of the study and a doctoral student in molecular, cellular and integrative physiology, said in an emailed statement that mice exposed to dietary changes and lowered oxygen levels took longer to find the target hole and made more mistakes than mice not subjected to these conditions.

Olson said they knew a relationship between the microbiome and the brain existed because previous research found that animals missing gut microbiota experienced changes in cognitive behavior. One 2019 study found that germ-free mice were worse at adapting to feelings of fear.

[Related: UCLA researchers find link between early-life adversity and stress in adulthood]

Olson said reduced oxygen levels were previously known to mimic aging and impair learning and memory.

Research has increasingly linked gut microbiota with cognitive and behavioral outcomes on the host, which may help scientists’ understanding of cognitive disorders like Alzheimer’s disease and other forms of dementia, Yang said.

These disorders are not solely explained by biology because there are environmental factors – like diet – that can also contribute to disease risk and manifestation, Yang added.

Yang said they also wanted to test relationships between the gut microbiome and environmental risk factors to see how they relate to these cognitive diseases, but the specifics remained unclear.

Ping Fang, a postdoctoral scholar in integrative biology and physiology and a co-author of the study, said their study looked at mice whose cognitive impairment was induced artificially in a lab. For other diseases, however, the impairment happens spontaneously, she said.

As diseases like dementia become more common, Yang said there is a critical need to continue research on brain-gut interactions because much is unknown about the causes of cognitive impairment.

“We are in dire need of cures,” she said.

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