Healthy centenarians display a more diverse and rich virome compared with young and older individuals
a, A phylogenomic tree of vOTUs based on 1,415 (out of 2,388) de novo assembled and 29,057 MGV (out of 37,946) vOTUs, created with IQtree and visualized using iToL v5 (https://itol.embl.de/). Predicted host-taxonomic phylum is indicated for each vOTU as either Firmicutes (green), Actinobacteria (orange), Bacteroidetes (yellow), Proteobacteria (blue), Verrucomicrobia (pink) and Desulfobacteriota (purple). Host color indications can be seen in the second ring around the tree. vOTUs not clustered with an MGV genome at species level are labeled undescribed vOTU (red leaf), otherwise as MGV (black leaf) shown in the third ring. Viral genera of interest (G7, G78 and G2) are indicated in the first ring. The prevalence (0–1) of each vOTU in the microbiome of centenarian, older and young individuals is indicated as orange, blue and gray bars (from the fourth ring outwards). Finally, vOTU enrichment (Wilcoxon rank sum test, one-sided, FDR corrected) on median TPM is indicated as a black rectangle between centenarian vs young, centenarian vs older and older vs young.
b, PCoA-based vOTU Bray-Curtis dissimilarity shows separation of centenarian samples from older and young individuals.
c,d, Boxplots of viral richness (the number of detected vOTUs in sample) (c) and Shannon diversity
(d) show significantly increased richness and diversity in centenarians (t-test, two-sided, *P < 0.05).
e, Abundance proportion summed for undescribed vOTUs and vOTUs similar to an MGV genome indicates that a larger proportion of read-mapping signal originates from vOTUs in centenarians (t-test, two-sided, *P < 0.05).
f, Abundance proportion summed by core virus (prevalence >10% across age groups) and individual viruses (prevalence <10% across age groups). To generate the plots in c–e, we included centenarian (n = 176 (153 individuals)), older individual (n = 110) and young (n = 44) metagenomic samples.
Credit: Nature Microbiology (2023). DOI: 10.1038/s41564-023-01370-6
We are pursuing the dream of eternal life. We fast to stay healthy. And each year, we spend billions of dollars on treatment to make sure we stay alive. But some people turn 100 years old all by themselves. Why is that?
Researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have set out to find the answer.
Studying 176 healthy Japanese centenarians, the researchers learned that the combination of intestinal bacteria and bacterial viruses of these people is quite unique.
"We are always eager to find out why some people live extremely long lives. Previous research has shown that the intestinal bacteria of old Japanese citizens produce brand new molecules that make them resistant to pathogenic—that is, disease-promoting—microorganisms. And if their intestines are better protected against infection, well, then that is probably one of the things that cause them to live longer than others," says Postdoc Joachim Johansen, who is first author of the new study.
Among other things, the new study shows that specific viruses in the intestines can have a beneficial effect on the intestinal flora and thus on our health.
"Our intestines contain billions of viruses living of and inside bacteria, and they could not care less about human cells; instead, they infect the bacterial cells. And seeing as there are hundreds of different types of bacteria in our intestines, there are also lots of bacterial viruses," says Associate Professor Simon Rasmussen, last author of the new study.
Joachim Johansen adds that aside from the important, new, protective bacterial viruses, the researchers also found that the intestinal flora of the Japanese centenarians is extremely interesting.
"We found great biological diversity in both bacteria and bacterial viruses in the centenarians. High microbial diversity is usually associated with a healthy gut microbiome. And we expect people with a healthy gut microbiome to be better protected against aging related diseases," says Joachim Johansen.
Once we know what the intestinal flora of centenarians looks like, we can get closer to understanding how we can increase the life expectancy of other people. Using an algorithm designed by the researchers, they managed to map the intestinal bacteria and bacterial viruses of the centenarians.
"We want to understand the dynamics of the intestinal flora. How do the different kinds of bacteria and viruses interact? How can we engineer a microbiome that can help us live healthy, long lives? Are some bacteria better than others? Using the algorithm, we are able to describe the balance between viruses and bacteria," says Simon Rasmussen.
And if the researchers are able to understand the connection between viruses and bacteria in the Japanese centenarians, they may be able to tell what the optimal balance of viruses and bacteria looks like.
Optimizing intestinal bacteria
More specifically, the new knowledge on intestinal bacteria may help us understand how we should optimize the bacteria found in the human body to protect it against disease.
"We have learned that if a virus pays a bacterium a visit, it may actually strengthen the bacterium. The viruses we found in the healthy Japanese centenarians contained extra genes that could boost the bacteria. We learned that they were able to boost the transformation of specific molecules in the intestines, which might serve to stabilize the intestinal flora and counteract inflammation," says Joachim Johansen.
Simon Rasmussen adds, "If you discover bacteria and viruses that have a positive effect on the human intestinal flora, the obvious next step is to find out whether only some or all of us have them. If we are able to get these bacteria and their viruses to move in with the people who do not have them, more people could benefit from them."
Even though this requires more research, the new insight is significant, because we are able to modify the intestinal flora.
"Intestinal bacteria are a natural part of the human body and of our natural environment. And the crazy thing is that we can actually change the composition of intestinal bacteria. We cannot change the genes—at least not for a long time to come. If we know why viruses and intestinal bacteria are a good match, it will be a lot easier for us to change something that actually affects our health," says Simon Rasmussen.
The study, "Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan," has been published in Nature Microbiology.
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