Viruses in the guts of centenarians may help them resist pathogens

New research suggests that centenarians — people who live to be at least 100 — have a diverse collection of viruses in their gut that could help protect them from infectious diseases. The findings, published today in Nature Microbiology, shed light on some of the biological pathways that may help centenarians live long, healthy lives. 

In the study, a team of researchers led by Joachim Johansen, Ramnik Xavier, Simon Rasmussen, and Damian Plichta at the Broad Institute of MIT and Harvard analyzed the gut viromes — communities of viruses within the gut — from 195 individuals from Japan and Sardinia. They found that centenarians had a greater diversity of bacteria and viruses in their guts. 

They also found that viruses found in centenarians increased the ability of the healthy gut bacteria to break down sulfate, which could help preserve the gut’s ability to fight bacterial infections.

The study adds to a growing body of evidence showing that the interactions between bacteria, viruses, and fungi in the gut play an important role in preventing age-related conditions. 

“This snapshot of how the virome interacts with gut microbiomes could tell us about how microbial and viral ecology evolves over the lifetime of a person,” said Ramnik Xavier, a core institute member, director of the Immunology Program, and co-director of the Infectious Disease and Microbiome Program (IDMP) at the Broad. “This offers an important starting point for uncovering the mechanisms behind how the gut ecosystem maintains health.” 

Xavier is also a professor of medicine at Harvard Medical School and Massachusetts General Hospital. He is a co-senior author on the study along with Rasmussen, a visiting scientist at the Novo Nordisk Foundation Center and an associate professor at the University of Copenhagen; and Plichta, a group leader in the IDMP at Broad.

A closer look

Previously, Xavier’s team found that intestinal bacteria in centenarians produced unique bile acids that could help keep infections at bay. Other researchers have found that bacteriophages — or viruses that infect bacteria — had an effect on cognition and memory in mice. But the role that the viruses play in the gut and aging in humans remains unknown, in part because viral DNA can be difficult to extract from complex samples.

In this study, the Broad team collaborated with researchers from Japan, including Kenya Honda, a professor of microbiology and immunology at the Keio University School of Medicine in Tokyo. They also teamed up with researchers from the University of Copenhagen to apply a deep-learning based framework to pull out viral information from metagenomes, or the DNA present in complex samples such as stool.

By homing in on viral genomes, the researchers compared the viromes of young adults over 18, older adults over 60, and centenarians aged 100 and over. The data came from previously published datasets in Japan and Sardinia, two regions with an unusually high proportion of centenarians. In centenarians, the team found not only more diverse bacteria and viruses, but also more viruses in the lytic life cycle, during which viruses are active and burst and kill the bacteria they infect — a phase that is more common in infants than adults. At least a quarter of the viruses found in centenarians encoded genes that support key stages of sulfate metabolism. The researchers think this could help sustain the integrity of the mucosal barrier, a highly selective collection of tightly-bound cells that allows the body to absorb nutrients in the gut while keeping bacteria and toxins at bay.

“It’s extremely exciting to work on the microbiome, including viruses, because there's so much diversity and so many unknown species,” Plichta said. “There's always something to discover, whether that’s new organisms or previously uncharacterized enzymes.”