Long-lived viruses caused gut bacteria to produce more hydrogen sulfide
New viral genera were found in the intestines of Japanese long-livers: most of them turned out to be phages associated with clostridia. As reported in the journal Nature Microbiology, phage-borne genes influenced the metabolism of sulfur and increased the conversion of methionine to homocysteine and sulfates and taurine to sulfides, including hydrogen sulfide. The gas probably helps long-livers maintain resistance to pathogens.
It is known that the gut microbiome of long-livers significantly differs from that of young and middle-aged people by its composition and metabolic level (for example, there is an increase in synthesis of secondary bile acids). These changes are thought to regulate gut function, protecting it from infection. However, it remains unknown what role gut viral communities, or virome, play in age-related changes in the microbiome. Bacterial viruses - bacteriophages - are of particular interest in this matter, since they are used for horizontal gene transfer - transduction.
However, some bacteriophages have lytic activity, that is, they can destroy the bacterial cell. Pro-inflammatory cytokines are known to trigger phage lytic cycles, which can maintain inflammation and lead to tissue aging. To find out how virome lytic activity changes with age, Damian Plichta of the Broad Institute studied the viral and bacterial gut communities of Japanese long-livers, older adults (over age 60) and young adults (over age 18).
The scientists first characterized the viral gut communities of long-livers-their virome. Using metagenomic binning and searching for proviruses in bacterial metagenomes, they analyzed the virome of 172 long-livers (one hundred years and older), 133 older adults and 61 young adults. Overall, of the 4,422 viral genera found, for 1,746, scientists were unable to find existing references in viral genome databases. Several statistical models showed a significant difference in virome compositions between long-livers and control groups.
Most of the new taxa were assigned to clostridium-specific phages, more specifically to the genus Ruminococcus. 483 taxa turned out to be specific for long-livers (they were found in 94% of long-livers). In particular, phage taxa associated with Clostridium scindens, Akkermansia muciniphila, Enterocloster bolteae and Parabacteroides distasonis dominated in virome in long-livers compared to control groups. At the same time, they had fewer viruses specific to Bacteroides and Faecalibacterium.
By counting the ratio between phages and bacteria, the scientists found that the virome in long-livers shifts toward increased lytic activity compared to younger people. However, a marker of inflammation, C-reactive protein, was not elevated in the blood of long-livers, which means that the lytic activity of the viruses did not lead to inflammation in the gut. The researchers suggested that the ratio of viruses to bacteria in the microbiome may be increased by lysis of specific bacteria.
In addition, the scientists found that due to transduction, the genes responsible for turning methionine into homocysteine and sulfate and taurine into sulfide predominate in the bacterial pangenome of long-livers. That is, in long-livers, the microbiome had great potential to produce homocysteine and hydrogen sulfide, which has protective properties: it reduces the risk of mucosal colonization by aerobic pathogenic bacteria.
This study brings new insights into the complex viral-bacterial relationships in the intestinal microbiomes of long-livers, which may help in the search for mechanisms of healthy aging. In addition, this knowledge may help develop methods to correct impaired gut microbiome homeostasis.
The gut microbiome can tell not only how old a person is, but also what he or she is suffering from. For example, scientists found that schizophrenia and depression patients have very similar bacterial communities.