The role, impact, and function of bacteriophages in gut microbiota are being researched, with results showing a world of possibilities yet to uncover. In recent years, there has been an abundance of research focusing on the gut microbiome. However, the focus has mainly been towards the bacterial population, as it is the largest population constituting the gut microbiota. The virome or the viral population has only recently begun to be looked at, specifically the role of bacteriophages in gut microbiota.
Bacteriophages in gut microbiota and improved cognition
Research conducted by a team of researchers who are affiliated with numerous institutions in Spain found evidence that the presence of certain bacteriophages in gut microbiota, helps improve executive function and memory in fruit flies, mice, and humans. The connection between the gut and brain has been investigated by many from a bacterial perspective. The presence of certain bacteria is shown to either promote or create a lack of certain mental functioning. However, in this recent study, the research investigated if the same link was evident with bacteriophages.
“Almost all papers are focused on the main components of the gut microbiota: the bacteria. The possible role of viruses has not been investigated. This would be the first paper relating bacteriophages in gut microbiome to cognition in mammals and fruit flies”, study co-author and University of Girona nutrition and metabolism researcher José Manuel Fernández-Real.
The study was focused on the members that normally dominate to gut virome portion of the gut; Microviridae and Caudovirales, particularly the family Siphoviridae. The fecal samples of 114 volunteers, and then another 942 volunteers were measured for the levels of the chosen bacteriophages. Each volunteer was given several cognitive and memory tests. Such tests included drawing a line threading a series of number-and-letter-labeled circles in a correct order and reciting a list of numbers in reverse order.
The results showed a correlation between higher levels of Caudovirales found in samples, in those volunteers who also performed better in the tests, compared to those volunteers whose samples showed higher levels of Microviridae, who performed worse in the tests, specifically the ability to learn and retain new information.
In the next phase, the researchers transplanted the fecal samples from human volunteers into mice. A series of memory tasks were performed as well as sequenced RNA from each mouse’s prefrontal cortex in order to measure gene expression. The researchers also noticed that genes associated with memory formation, synaptic plasticity, and neuronal development were upgraded in the prefrontal cortices of the mice. It is important to note that apart from transplanting the bacteriophages, the fecal transplants also contained 1385 taxa from the human donor gut microbiota, of which 216 were not found in the control group. This made it hard to identify whether the better performance was solely linked to the higher presence of Caudovirales.
Following this, the researchers wanted to determine whether the bacteriophages may have a direct influence on physiology. To do this, they used fruit flies that were fed a diet rich in whey powder, that contains Siphoviridae bacteriophages. The fruit flies were then given a memory test which consisted of them learning to avoid bitter foods. Those flies that were fed with the whey powder, learned to avoid bitter foods, showing that they were able to retain memories of their aversion better than those fruit flies that were not fed the bacteriophage-rich diet. Transcription analysis revealed that the fruit flies, just like the mice, had upregulation of genes that are involved in memory formulation, plasticity, and neurodevelopment.
The researchers then investigated the path by which the two bacteriophages end up in our gut, by studying various types of food. For both bacteriophages, dairy products seemed to result as the most common route to the human gut.
Although the researchers do not claim that their work is solid proof on bacteriophages in gut microbiota having a direct impact on cognitive abilities, it can, however, suggest being a likely possibility. More work is certainly required for proof; however, it does certainly open a lot of potential too.
Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans