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A new method for multiplying bacterial viruses, or phages, in a bioreactor has been developed in a collaboration between researchers at Taltech and the University of Copenhagen. Viral preparations can be used to restore the gut microbiota. Positive effects of the propagated virome were demonstrated in animal studies on mice and three papers were published in the field’s top journals.
The complex gut microbiota, which includes bacteria and viruses, influences human health in a number of ways, from nutrient metabolism to interactions with the immune and nervous systems as well as hormonal processes. Dysbiosis of the gut microbiota would lead to several chronic health problems. Decreased overgrowth of potentially pathogenic taxa is often associated with a modern lifestyle characterised by low physical activity, refined and ultraprocessed foods, irregular eating and sleeping patterns, use of antibiotics, environmental pollution and stress.
Kaarel Adamberg, the lead author of the study and senior research scientist at the Taltech Department of Chemistry and Biotechnology, explains: “Preparates of bacterial viruses can be used to modulate the gut microbiota to control the growth of both beneficial and harmful bacteria. Phage therapy based on single phages has been studied for over a century and specific preparations have been developed. However, altering the whole community with individual phages is ineffective. Consequently, it has been suggested that a combination of viruses, or virome, could be used to modify the gut microbiota substantially or considerably or significantly.”
The effect of the virome preparation on a pathogenic bacterium Clostridioides difficile, which causes fatal diarrhoea, was studied. This bacterium is a serious problem during antibiotic treatment in hospitals since antibiotics administered against pathogensare not very selective. Thus, they also affect the so-called “beneficial” bacteria and disrupt the balance of the gut ecosystem. In some cases, the only effective treatment is the transfer of the healthy person’s (donor) faecal matter to the colon of the infected person, known as faecal microbiota transplantation (FMT). However, there are a number of risks associated with FMT, as even carefully controlled faecal material can contain pathogens and disease-causing viruses.
“We propagated faecal communities (bacteria and viruses) in a bioreactor in a gut-like and oxygen-free (anaerobic) environment to diminish the amounts of eukaryotic viruses. The resulting culture was filtered to separate all bacterial cells and concentrate only the bacterial viruses (phages). This type of filtrate is safer because it no longer contains bacteria nor eukaryotic viruses that can cause human diseases in their active form. The analyses confirmed that the bacterial virome produced in the bioreactor was highly diverse. Moreover, viromes with various compositions and large amounts can be produced by cultivation of gut microbiota in the bioreactor,” says Kaarel Adamberg, describing the method developed.
Viral preparations produced in Taltech’s laboratory were further tested in two animal studies at the University of Copenhagen. The effectiveness of the treatment of mice infected with Clostridioides difficile with the viral preparation and the survival rate of the mice were comparable to those of the control group. In another experiment, the viral preparation was shown to alleviate the metabolic syndrome in obese mice.
The studies were published in the journals iScience, Nature Communications and Microbiome.
Video introducing the article series: https://www.researchsquare.com/article/rs-4804568/v1
This article was written by Kaarel Adamberg, Senior Researcher, Department of Chemistry and Biotechnology TalTech.
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