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Study Finds Distinct, Diverse Gut Viromes in Centenarians

NEW YORK – A Broad Institute- and University of Copenhagen-led team has uncovered distinct gut virus community features in individuals who have reached at least 100 years old in Japan or Sardinia, including an uptick in viral diversity and altered bacterial interactions prompting metabolic shifts.

"We found that the human gut virome in centenarians represents a rich and diverse community with unique viral populations that interact with enriched bacterial taxa identified in centenarians," co-senior and -corresponding authors Damian Plichta and Ramnik Xavier, infectious disease and microbiome researchers at the Broad, and Simon Rasmussen, with the University of Copenhagen and the Broad, and their colleagues wrote in Nature Microbiology on Monday.

For their analyses, the researchers started with published metagenomic sequences representing 195 fecal samples from 172 centenarians in Japan and Sardinia, using a virus and prophage sequence detection pipeline to characterize gut virome patterns in the centenarians. Those gut virus community patterns were then compared with gut virome features found in metagenomic sequences for 61 young adults between the ages of 18 and 55 years old, and for 133 non-centenarian individuals over 60.

"As centenarians represent a surprisingly robust population with a decreased susceptibility to age-related diseases and infection compared with people decades younger," the authors explained, "the key to their longevity remains a topic of interest."

Overall, the team's analyses revealed enhanced gut virome diversity in the centenarians relative to the non-centenarian adults, while highlighting Clostridia bacteria-associated viral genera and other viral operational taxonomic units not reported in the past.

When they delved deeper into viral interactions with bacteria in the centenarian gut, the investigators saw a shift away from so-called lysogenic interactions toward interactions that increase bacterial lysis, together with a boost in auxiliary metabolic genes from bacterial pathways involved in sulfate metabolism and other microbial metabolic changes.

"[W]e found that the centenarian virome contributes to key steps in sulfur metabolic pathways mediated by gut bacteria, especially the conversion of methionine to homocysteine," the authors reported. "This in turn revealed that centenarians harbor a microbiome configuration with greater potential for converting methionine to homocysteine, sulfate to sulfide, and taurine to sulfide."

The centenarian microbiome data also pointed to a lytic virus-bacteria interaction-related rise in the virus-to-bacteria ratio in the gut compared to that found in elderly, non-centenarian individuals, the researchers noted — dynamics that were explored further in the current study with the help of metagenomic data for hundreds of samples collected from infants and adults for efforts in Finland and Tanzania, respectively.

"Altogether, our analysis confirmed that temperate viruses expand over time in the infant gut and manifest into a stable lysogenic community throughout adulthood," the authors wrote. "We further identified a return to an increased lytic community in very old individuals."

They noted that most viral proteomes — an estimated three-quarters — are yet to be characterized, and argued that "sequencing efforts of both bulk and viral particle-specific enrichment samples combined with long-read sequencing technology will be of immense value for continuing the delineation of viral populations that may benefit human longevity."