New research associates the presence of Caudovirales in gut microbiota to an improvement in cognitive functions and memory in humans, mice and flies. The results show that bacteriophages present in the gut microbiota influence the relationship between the microbiome and the brain. The article, published in the journal Cell Host & Microbe, was led by Dr. Jordi Mayneris-Perxachs and Dr. José Manuel Fernández-Real, from the Nutrition, Eumetabolism and Health group at the Josep Trueta Biomedical Research Institute of Girona (IDIBGI) and CIBEROBN.
The work has been carried out in collaboration with the Neuropharmacology research group led by Dr. Rafael Maldonado at Pompeu Fabra University and attached to the Hospital del Mar Medical Research Institute (IMIM); the Human Microbiome group of Drs. Andrés Moya and Vicente Pérez-Brocal, from the FISABIO Foundation, the Institute of Integrative Systems Biology (I2SysBio) of the University of Valencia and the Spanish National Research Council (CSIC), and CIBERESP; and the University of Alicante (UA).
Bacteriophages, a type of virus that replicates within bacteria, represent one of the largest gaps in the knowledge of the human microbiome. This research has focused on the study of two types of bacteriophages that are prevalent in our gut microbiota: Caudovirales and Microviridae.
In a sample of 114 people, which was later expanded to 942 subjects (participants in the IDIBGI’s Ageing Imagenoma Project), the researchers found that “individuals with more Caudovirales performed better at executive processes and verbal memory, while the presence of higher levels of Microviridae, on the other hand, was associated with a greater deterioration in the brain’s executive abilities”, states Dr. Fernández-Real, head of the Nutrition, Eumetabolism and Health group of the IDIBGI and CIBEROBN, who is also Head of the Endocrinology Section at Hospital Dr. Josep Trueta in Girona and director of the Department of Medical Sciences at the University of Girona.
Dairy products, a possible means of acquiring Caudovirales
To find out how people can access these viruses, the researchers conducted food surveys on the participants to find out about their diet. Interestingly, individuals who had more Caudovirales in their gut microbiota consumed more dairy products on a regular basis. This finding is supported by the scientific literature in this area: some previous research indicated that people who ate more dairy produce had better cognitive functions.
In order to further reinforce the result, an experiment was performed in mice, using the microbiota present in the different samples of human faeces, transplanting it into the intestine of the rodents. “Mice that received a microbiota rich in Caudovirales performed better cognitively than other mice, with significant improvements in spatial memory and emotional memory”, asserts Dr. Rafael Maldonado (UPF-IMIM).
A second confirmatory experiment was conducted in fruit flies (Drosophila melanogaster) as an animal model. First, one group of flies was fed whey powder, and it was seen to have greater memory capacity than the other group of Drosophila that ingested sterilized, therefore virus-free, whey powder. The experiment was repeated, but in this case the feeding of the flies was supplemented with isolated bacteriophages. The results were replicated again. Observing a group of genes in the fly’s brain, the authors found that the presence of Caudovirales upregulated the genes associated with memory.
The results of this study reinforce the consideration of bacteriophage viruses as influential actors in the relationship between the human microbiome and the brain. In addition, the work opens the way to new lines of research, such as the study of possible dietary supplements with this virus in isolation to improve people's cognitive abilities.
Reference article: https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(22)00049-X
