For today, a topic I haven’t had a chance to write about in months: the virome. Published last week in Cell Host & Microbe is an article that shows that a specific bacteriophage has been found to improve executive function and memory in both animals and in humans.[i] Apparently, previous research has shown that the virome, like the bacterial microbiome, changes with age: from the family Cuadovirales, Microviridae goes up and Siphoviridae goes down. (What is kind of extraordinary is that in animals, this also happens when they are fed high fat diets!)
As you know from previous posts on this topic (see here for just one example), bacteriophages (phages for short) are viruses that infect bacteria. If you remember, they are being studied as a means of manipulating the gut bacteria as well as being used in lieu of antibiotics. In this case, the scientists were surprised to find a strong negative association between specific Cuadovirales and multiple aspects of folate metabolism, including the use of vitamins B2 and B6 in the folate cycle, as well as DNA repair mechanisms; however, some bacterial pathways associated with folate metabolism were increased. For example, a gene was upregulated tha,t in humans, is known to affect neuroplasticity, neurological development and memory retention.[ii]
The researchers tested this all in a cohort of 115 humans. They found that those with increased levels of specific Cuadovirale and Siphoviridae in their gut microbiomes had better performance in executive processes and verbal memory. Those with increased levels of Microviridae, which as noted above, are known to increase with age, had greater impairment in executive abilities. Some differences in responses were noted between men and woman. The scientists repeated the study using a cohort of almost 1000 people (942). The results were even more pronounced in men, interestingly: Cuadovirales were noticeably associated with improvements in executive functioning, short-term and long-term memory and information processing speeds.
Transplanting microbiota from human donor with higher levels of specific Caudovirales led to improved memory test scores in mice. They also tested this in flies (they use aversive tastes) and believe it or not, and found the same type of results.
The paper points out that in multiple cohorts, they found a positive association between Cuadovirales and various species of probiotic bacteria, including various strains of Lactobacillus and streptococcus. Both are associated with fermented dairy products (i.e. yogurt, etc.) as well as with human milk. The paper states that, “Consistently, we found positive associations between specific Caudovirales levels and dairy product consumption and medium-chain fatty acids which are naturally occurring in dairy fat, as well as between specific Caudovirales-linked lactic acid bacteria and dairy products. On the contrary, the Microviridae family had negative associations with medium-chain fatty acids. Interestingly, supplementation with medium-chain fatty acids has shown to improve synaptic plasticity and cognitive function in mice and humans.”
The upshot is that in the not-very-distant future, direct supplementation of certain phages may well be used to improve our health, and to treat diseases of aging: “All these findings may have implications in the design of dietary interventions targeted at improving cognitive and memory dysfunction.”
[i] Mayneris-Perxachs, J, et. al. Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans. Cell Host & Microbe. 2022. https://doi.org/10.1016/j.chom.2022.01.013.