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Recent research has shown that changes in the gut microbiota – the trillions of bacteria and other microbes that live in the intestines – can affect the brain and behavior. Now, a study by scientists at UCLA could shed light on how and why this phenomenon occurs.
In the experiment, which was conducted with mice, the researchers found that gut microbes can exacerbate the effects of cognitive impairment due to the way they affect the hippocampus, the region of the brain that is essential for memory. and learning. They found that the concentration of a group of bacteria called Bilophila increased dramatically in the gut microbiota of mice fed a ketogenic diet – high in fat and low in carbohydrates – and were intermittently starved of oxygen, creating a condition called hypoxia. .
Scientists also found that a ketogenic diet, hypoxia, and treatment with a species of Bilophila called Bilophila wadsworthia impair the hippocampus, leading to reduced cognitive abilities in mice.
The research is published in the peer-reviewed journal Cell Host & Microbe.
The researchers gave several mice a ketogenic diet and others a standard diet. Then all of the mice were given reduced oxygen levels for five consecutive days, then given four days to recover. Depriving animals of a little oxygen was a way for scientists to induce cognitive impairment, in order to mimic cognitive impairment in humans that can be caused by neurological diseases or aging.
Next, scientists observed their ability to navigate a maze. When trying to get out of a maze, mice on the ketogenic diet made an average of 30% more mistakes than mice on the standard diet. (The range of difference between the two groups was 25% to 75%.)
The researchers also assessed whether the different diets alone could cause a change in cognitive behavior in mice that were not deprived of oxygen. In this experiment, there was no appreciable difference in the ability of mice to exit the maze depending on whether they were on a ketogenic diet or a standard diet, indicating that the negative impact on cognitive abilities was not. is produced only in combination with oxygen deprivation.
“These findings highlight the ability of different environmental factors to interact together to impact cognitive behavior in mice,” said lead author Christine Olson, a UCLA graduate student.
Next, the researchers studied what would happen if they depleted the mice’s microbiota before giving them a ketogenic diet and exposing them to hypoxia. Interestingly, mice with depleted microbiota initially made significantly fewer mistakes in the maze than mice exposed to hypoxia and given a ketogenic diet, but did not initially undergo changes in the maze. their microbiota.
“This suggests that the microbes associated with the ketogenic diet and hypoxia may contribute to the detrimental effects on cognitive impairment,” Olson said.
The authors determined that Bilophila wadsworthia changes genes that are turned on or off in the hippocampus, and that the bacteria reduce normal cell signaling in the hippocampus.
“Bilophila wadsworthia disrupted hippocampal activity and cognitive behavior in the same way as hypoxia and the ketogenic diet together,” Olson said. She added that given the hippocampus’s important role in learning and memory, the changes offer clues as to how Bilophila influences cognitive behavior.
Scientists are just discovering microbial species that can affect behavioral changes in mice and other animals, Hsiao said. She added that it will be important to study more specifically how microbial species can affect the brain – for example, through cellular changes that occur in response to microbes.
Cognitive impairment affects millions of people over the age of 65 and is associated with a wide variety of chronic metabolic, immunological and neurodegenerative disorders, such as Alzheimer’s disease. Elaine Hsiao, De Logi professor of biological sciences at UCLA and associate professor of digestive diseases at UCLA’s David Geffen School of Medicine, said the new study could be an important step towards learning about the microbes that affect or impair cognitive abilities.
“Early identification of risk factors is essential to enable early detection and intervention for cognitive impairment,” said Hsiao, lead author of the article.
Hsiao added that more research is needed to determine whether other gut microbes besides bilophila might also affect cognitive abilities and whether the microbiota might influence cognitive decline in humans.
Reference: Olson CA, Iñiguez AJ, Yang GE, et al. Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia. Microbe host cell. 2021; 0 (0). doi: 10.1016 / j.chom.2021.07.004
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