Gut Microbiome Heritability

Analyzing data from a large twin study, researchers have homed in on how host genetics can shape the gut microbiome.

By Tracy Vence | November 6, 2014

WIKIMEDIA COMMONS, TWINSUKPrevious research suggested host genetic variation can influence microbial phenotype, but an analysis of data from a large twin study published in Cell today (November 6) solidifies the connection between human genotype and the composition of the gut microbiome. Studying more than 1,000 fecal samples from 416 monozygotic and dizygotic twin pairs, Cornell University’s Ruth Ley and her colleagues have homed in on one bacterial taxon, the family Christensenellaceae, as the most highly heritable group of microbes in the human gut. The researchers also found that Christensenellaceae—which was first described just two years ago—is central to a network of co-occurring heritable microbes that is associated with lean body mass index (BMI). They determined that introducing at least one member this bacterial family was associated with reduced weight gain in mice.

“To me, the most interesting and exciting part was their demonstration of heritability of the microbiome,” said Martin Blaser, the director of the Human Microbiome Program at New York University Langone Medical Center who was not involved in the work. “I’ve been postulating this for some time, so it’s very nice to find evidence for this.”

“Our primary goal was to establish, once and for all, whether there was an effect of host genotype on the composition of the gut microbiome,” Ley, an associate professor of microbiology, told The Scientist. “We thought perhaps there would be a few taxa here and there that might be heritable, but [a] list popped up, and it started getting more and more interesting.”

Of particular interest was the family Christensenellaceae, which was the most heritable taxon among those identified in the team’s analysis of fecal samples obtained from the TwinsUK study population.

While microbiologists had previously detected 16S rRNA sequences belonging to Christensenellaceae in the human microbiome, the family wasn’t named until 2012. “People hadn’t looked into it, partly because it didn’t have a name . . . it sort of flew under the radar,” said Ley.

Ley and her colleagues discovered that Christensenellaceae appears to be the hub in a network of co-occurring heritable taxa, which—among TwinsUK participants—was associated with low BMI. The researchers also found that Christensenellaceae had been found at greater abundance in low-BMI twins in older studies.

To interrogate the effects of Christensenellaceae on host metabolic phenotype, the Ley’s team introduced lean and obese human fecal samples into germ-free mice. They found animals that received lean fecal samples containing more Christensenellaceae showed reduced weight gain compared with their counterparts. And treatment of mice that had obesity-associated microbiomes with one member of the Christensenellaceae family, Christensenella minuta, led to reduced weight gain.

Although interesting, the team’s experimental results in mice are still preliminary, according to Blaser. Patrice Cani, a leader of the Metabolism and Nutrition Research Group at Université catholique de Louvain in Belgium, agreed. “The genetic association is clear,” said Cani. “The impact of these bacteria on body weight is less clear.”

Cani said that by tapping into the TwinsUK study population, the researchers were able to find associations that had previously gone undetected. “We’ve known for almost 10 years that genetic background may have an impact of the gut microbiota,” he told The Scientist. “Here, they have a very high number of subjects [and have] finally come to a conclusion.”

Ley and her colleagues are now focusing on the host alleles underlying the heritability of the gut microbiome. “We’re running a genome-wide association analysis to try to find genes—particular variants of genes—that might associate with higher levels of these highly heritable microbiota.  . . . Hopefully that will point us to possible reasons they’re heritable,” she said. “The genes will guide us toward understanding how these relationships are maintained between host genotype and microbiome composition.”

J.K. Goodrich et al., “Human genetics shape the gut microbiome,” Cell, doi:10.1016/j.cell.2014.09.053, 2014.

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Avatar of: Brent Beach

Brent Beach

Posts: 9

November 7, 2014

The article lost some text here - "hub in a network of co-The researchers"

After co-

Avatar of: Bob Grant

Bob Grant

Posts: 1031

Replied to a comment from Brent Beach made on November 7, 2014

November 7, 2014

Thanks for reading and spotting the glitch, Brent.

The missing text has been added back to the article.

The Scientist

Avatar of: Mounthell


Posts: 53

November 7, 2014

Strictly speaking, describing this dynamic as "Gut Microbiome Heritability" is gross misinterpretation. No microbes are inherited, only the auspicious conditions mentioned by Darwin, the environment including substrate.

There is a wealth of literature on the staged colonization of bacter on/in metazoans: luminescent vibrio fischeri in the Bobtail squid, the staged microbial colonization of human neonate gut and so on.

This story, including the entirety of such phenomena, is not about genetic process. This is basic, unadorned (primary) ECOLOGICAL SUCCESSION into prepared substrate. It's grotesquely past time for biology to have left the mind-sucking centralized paradigm of mid-20th century with its eternal sunshine of the idiot's delight, the "gene," and wriggle ashore to the 21st.

Avatar of: Alexandru


Posts: 97

November 8, 2014

The only real problem for The Scientist is to understand the maternal and paternal soul feedback and I say that the "Microbiome Heritability" means the all life data transfer from ancestors to the successors trough mitochondria inheritance. That means the genetically information modulated with the transgression effects memorized on maternal aura (living soul) and the paternal string (life giving spirit - Paul Hebrew 4.12 and 1 Corinthians, 15.45-47).

Based on Adam mtDNA inheritance, observed only at the puberty only in "born boy's" seminal liquid (not in vitro made), I have developed a new bio-communication theory, Mitochondrial Adam DNA data transmission theory - ISBN 978-606-92107-1-0, as complement of Eve mtDNA theory.




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