Missing link between dietary sugar and memory impairment may be in the gut

April 5, 2021

The link between too much sugar and mental changes is getting clearer. (Unsplash/Sharon McCutcheon)

After finding that a high-sugar diet early in life leads to both cognitive impairment and changes in the gut microbiome in adult rats, researchers were able to identify a single genus of gut bacteria as a causal connection between the latter two factors.

The study, published March 31 in Translational Psychiatry, adds to a growing body of evidence of a critical relationship between gut microbiota and neurocognitive development in mammals.

This relationship is a growing topic in biological research. Studies in mice have found that a Western diet, high in saturated fat and added sugar, changes the permeability of the gut and makes the brain more vulnerable to toxins produced by bacteria in the gut. Other studies have found that general depletion of the gut microbiome can cause anxious behaviors and change gene expression within the amygdala, the part of the brain involved in experiencing emotion.

However, unlike much of this other research, the authors of this study were able to connect this relationship to a specific bacterial population.

"Other researchers have been investigating microbiome brain relationships, so we're not the first to do that by any stretch, but what we did was look at the bacteria that changed in the sugar-fed animals," said senior author Scott Kanoski, an associate professor of biological sciences at the University of Southern California. "And then we looked at whether any of those changes were related or correlated with the memory impairment."

To identify a causative rather than a correlative relationship between gut bacteria and cognitive impairment, the researchers completed their research in several steps. The first was using a study model from their previous work to establish how sugary diets affect impairment.

"We give rats access to a sugar-sweetened beverage throughout the entire juvenile and adolescent period of their life. It's basically the same sugar concentration as a soda or sweetened iced tea," Kanoski said. "And then when they're young adults, that's when we start testing their memory function and various other metabolic outcomes."

They found that the rats who had been fed sugar performed worse in several object recognition tests, specifically those associated with the function of the hippocampus, a part of the brain associated with learning and memory described by Kanoski as a "canary in a coal mine of diet-induced memory impairment."

To connect this impairment to the gut, the team then looked at how the gut microbiome changed in the rats that were fed sugar. Though there were many changes, only a certain population of bacteria from the genus Parabacteroides seemed to be correlated with the cognitive impairment.

To test this correlation, the team transplanted large amounts of this bacteria into rats that had not been fed sugar. They found that not only did the same hippocampal memory impairments occur in these rats, the animals also suffered impairments in memory processes related to the perirhinal-cortex, suggesting a dose-dependent relationship between Parabacterioides and brain impairment.

"It could be that the more of this bacteria is present, the more neural substrates are being negatively affected that are involved with neurocognition," Kanoski said.

The final step of the research involved performing a genetic analysis to see what groups of genes were changed by sugar and by these bacteria. Kanoski emphasizes that these analyses are broad, making them more useful for future researchers to build upon than for making any specific mechanistic claims now.

However, they did find changes in genes affecting the dopamine synaptic signaling pathway, which is connected to sensations of pleasure. This may prove significant in future research, as sugar is already known to disrupt dopamine levels.

While the researchers emphasize that there are many more factors at play here than just one genus of bacteria, these results do suggest a causal relationship between the sugar, the bacteria and the cognitive impairment. With this relationship established, the team is next interested in investigating the extent to which these effects may be reversible, either by diet or exercise.

But for now, this work forms an important causal link between factors that until now have been studied primarily as a correlation, paving the way for future research to further clarify these relationships.

"One thing that I would encourage future researchers to do is move beyond the correlation and try to do manipulations of the bacteria," Kanoski said. "For procedural reasons, it's not so easy to do that, but I do think the field would benefit from advanced ways to target specific bacteria. I would love to see that happen but we're not quite there yet."

The study, "Gut microbial taxa elevated by dietary sugar disrupt memory function," published March 31 in Translational Psychiatry, was authored by Emily E. Noble, Ruth Schade and Claire de La Serre, University of Georgia; Christine A. Olson, Yen-Wei Chen, Xia Yang and Elaine Y. Hsiao, University of California, Los Angeles; and Elizabeth Davis, Linda Tsan, Clarissa Liu, Andrea Suarez, Roshonda B. Jones and Scott E. Kanoski, University of Southern California. 

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