Gut bacteriophages associated with improved cognitive function and memory in both animals and humans

A growing body of evidence has implicated gut bacteria in regulating neurological processes such as neurodegeneration and cognition. Now, a study from Spanish researchers shows that viruses present in the gut microbiota can also improve mental functions in flies, mice, and humans.

Credit: CDC.

They easily assimilate into their human hosts — 8% of our DNA consists of ancient viruses, with another 40% of our DNA containing genetic code thought to be viral in origin. As it stands, the gut virome (the combined genome of all viruses housed within the intestines) is a crucial but commonly overlooked component of the gut microbiome.

But we’re not entirely sure what it does.

This viral community is comprised chiefly of bacteriophages, viruses that infect bacteria and can transfer genetic code to their bacterial hosts. Remarkably, the integration of bacteriophages or phages into their hosts is so stable that over 80% of all bacterial genomes on earth now contain prophages, permanent phage DNA as part of their own — including the bacteria inside us humans. Now, researchers are inching closer to understanding the effects of this phenomenon.

Gut and brain

In their whitepaper published in the journal Cell Host and Microbe, a multi-institutional team of scientists describes the impact of phages on executive function, a set of cognitive processes and skills that help an individual plan, monitor, and successfully execute their goals. These fundamental skills include adaptable thinking, planning, self-monitoring, self-control, working memory, time management, and organization, the regulation of which is thought, in part, to be controlled by the gut microbiota.

The study focuses on the Caudovirales and Microviridae family of bacteriophages that dominate the human gut virome, containing over 2,800 species of phages between them.

“The complex bacteriophage communities represent one of the biggest gaps in our understanding of the human microbiome. In fact, most studies have focused on the dysbiotic process only in bacterial populations,” write the authors of the new study.

Specifically, the scientists showed that volunteers with increased Caudovirales levels in the gut microbiome performed better in executive processes and verbal memory. In comparison, the data showed that increased Microviridae levels impaired executive abilities. Simply put, there seems to be an association between this type of gut biome and higher cognitive functions.

These two prevalent bacteriophages run parallel to human host cognition, the researchers write, and they may do this by hijacking the bacterial host metabolism.

To reach this conclusion, the researchers first tested fecal samples from 114 volunteers and then validated the results in another 942 participants, measuring levels of both types of bacteriophage. They also gave each volunteer memory and cognitive tests to identify a possible correlation between the levels of each species present in the gut virome and skill levels.

The researchers then studied which foods may transport these two kinds of phage into the human gut -results indicated that the most common route appeared to be through dairy products.

They then transplanted fecal samples from the human volunteers into the guts of fruit flies and mice – after which they compared the animal’s executive function with control groups. As with the human participants, animals transplanted with high levels of Caudovirales tended to do better on the tests – leading to increased scores in object recognition in mice and up-regulated memory-promoting genes in the prefrontal cortex. Improved memory scores and upregulation of memory-involved genes were also observed in fruit flies harboring higher levels of these phages.

Conversely, higher Microviridae levels (correlated with increased fat levels in humans) downregulated these memory-promoting genes in all animals, stunting their performance in the cognition tests. Therefore, the group surmised that bacteriophages warrant consideration as a novel dietary intervention in the microbiome-brain axis.

Regarding this intervention, Arthur C. Ouwehand, Technical Fellow, Health and Nutrition Sciences, DuPont, who was not involved in the study, told Metafact.io:

“Most dietary fibres are one way or another fermentable and provide an energy source for the intestinal microbiota.” Leading “to the formation of beneficial metabolites such as acetic, propionic and butyric acid.”

He goes on to add that “These so-called short-chain fatty acids may also lower the pH of the colonic content, which may contribute to an increased absorption of certain minerals such as calcium and magnesium from the colon. The fibre fermenting members of the colonic microbiota are in general considered beneficial while the protein fermenting members are considered potentially detrimental.”

It would certainly be interesting to identify which foods are acting on bacteriophages contained within our gut bacteria to influence cognition.

Despite this, the researchers acknowledge that their work does not conclusively prove that phages in the gut can impact cognition and explain that the test scores could have resulted from different bacteria levels in the stomach but suggest it does seem likely. They close by stating more work is required to prove the case.

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