More genes in the human microbiome than stars in the observable universe

Rich Haridy

A team of US scientists is embarking on an immense project to catalog all the genes in the collective human microbiome. In the team’s first published study an astounding 46 million genes have been chronicled from just 3,500 human microbiome samples. Half of those genes are unique to single human samples.

“Space is big. Really big. You just won’t believe how vastly hugely mindbogglingly big it is. I mean you may think it’s a long way down the road to the chemist’s, but that’s just peanuts to space.”

Douglas Adams, The Hitchhiker’s Guide to the Galaxy

Astronomers suggest there may be about one billion trillion stars in the observable universe. Trying to fathom a universe that mind-bendingly large is virtually impossible, and now a new study is suggesting the human microbiome is operating on similar levels of complexity, but on a vastly smaller scale. The research, from Harvard Medical School and the Joslin Diabetes Center, suggests the bacteria living inside us may collectively contain more novel genes than there are stars in the observable universe.

We know inside every human body lives trillions of bacteria. Many estimates have found there to be more bacterial cells than human cells in a body – up to 10 times more in fact. While the gut microbiome comprises the largest volume of microbial residents in a human body, there are a variety of other specific communities of bacteria to be found, including oral, skin and lung microbiomes.

Perhaps one of the most exciting areas of research in the 21st century is our growing understanding of the influence these microbes have on our overall health. We are discovering how deeply symbiotic the relationship is between our general health and these bacterial influencers, however, the majority of research to date has just focused on links between certain bacterial species and disease.

This, of course, is an important start, but Chirag Patel from Harvard Medical School’s Blavatnik Institute, suggests the vast genetic differences within single bacterial species could be fundamental in understanding how disease is related to microbial activities.

“Just like no two siblings are genetically identical, no two bacterial strains are genetically identical, either,” says Patel. “Two members of the same bacterial strain could have markedly different genetic makeup, so information about bacterial species alone could mask critical differences that arise from genetic variation.”

In 2003 scientists officially completed the epic project of mapping the entire human genome. While debate on the final tally is ongoing, there seems to be roughly between 20,000 and 25,000 protein-coding genes in the human genome.

The new study analyzed 3,500 human microbiome samples, primarily from the gut and mouth. The researchers described the genetic heterogeneity of the results as “staggering,” discovering nearly 46 million “non-redundant genes.” Even more striking was the finding that around 50 percent of all the genes identified were unique to a single sample. Called singletons, these highly specific genes seem to serve specialized functions.

“Some of these unique genes appear to be important in solving evolutionary challenges,” says Braden Tierney, first author on the new study. “If a microbe needs to become resistant to an antibiotic because of exposure to drugs or suddenly faces a new selective pressure, the singleton genes may be the wellspring of genetic diversity the microbe can pull from to adapt.”

This vast genetic diversity uncovered in the study was somewhat unexpected. The researchers hypothesize this incredible heterogeneity as related to the ability of bacteria to quickly evolve their DNA in response to environmental conditions. What this essentially means is that a single bacterial species may be quite genetically different from person to person, amplifying the complexity in developing simple therapeutic outcomes from microbiome research.

Co-author on the study, Alex Kostic, suggests this points to a future where precision treatments for individuals may have to account for the unique genetic make up of their microbiome.

“Such narrowly targeted therapies would be based on the unique microbial genetic make-up of a person rather than on bacterial type alone,” adds Kostic.

The researchers have created a searchable website to openly catalog their discoveries. Titled The Universe of Microbial Genes, this database is just the beginning in a dauntingly long process to track all the genes in the collective human microbiome. Early estimates as to exactly how many unique genes there may be range from a conservative 232 million, to numbers that quickly become so absurdly large they mirror calculations regarding the amount of stars in the observable universe.

If anything, this project affirms how astonishingly complex microbiome science is turning out to be. It is increasingly clear that bacteria play an incredibly important role in our bodies, from modulating our immune system, to helping us digest food. But finding ways to turn these understandings into therapeutic treatments may be vastly more complicated than many previously suspected.

“Ours is a gateway study, the first step on a what will likely be a long journey toward understanding how differences in gene content drive microbial behavior and modify disease risk,” says Tierney.

The new research was published in the journal Cell Host & Microbe.

Bron: Harvard Medical School

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