Why do we gain weight or remain slim? Genes, microbes and now genes for microbes

You know that a tendency to put on pounds is partly the fault of genes. You’ve heard that gut microbes are involved in obesity too, although that’s a complicated and uncertain story. Now a twin study is showing that genes influence just which microbes are numerous in the gut—and that some of these microbes form a kind of network that seems to accompany being lean.

“Our results represent strong evidence that the abundances of specific members of the gut microbiota are influenced in part by the genetic makeup of the host,” the researchers say in a paper Cell published November 6. Furthermore, they report, this network of microbes was more common in people with low body mass index—lean people—compared with weightier folks.

Researchers based at Cornell examined feces from more than 400 twin pairs and showed that some microbe families are more “heritable” than others. This doesn’t mean that the microbes are inherited in the way genes are. It means that particular genes–so far it is not known just which genes—seem to be encouraging the growth of particular microbial populations. It’s the best evidence so far that the human gut microbiome—which is partly determined by diet—is also shaped by genes.

The most “heritable” microbes were identified because they were more often found in identical twins than in fraternal twins. Identical twins, you’ll recall, are made from the same fertilized egg and therefore have the same genomes. Fraternal twins are made from two fertilized eggs. They share no more genes than any other pair of siblings—just 50 percent on average.

Meet a new family of bacteria

The most “heritable” of the microbes were bacteria from a little-known family called Christensenellaceae. They were more common in the identical twin pairs than in fraternal twins, an indication that genes are important for building some gut microbe populations.

Christensenellaceae also lie at the hub of a microbe network that includes other heritable bacteria and certain members of the Archaea. (The Archaea are single-celled organisms that may look a bit like bacteria but have been recognized as a separate Kingdom of life since the 1970s. Archaea are often called extremophiles because they live in places like the super-hot vents deep in the oceans. But in fact they live everywhere. The Archaea found in this study were from a group called methanogens. Methanogens live in the guts of many animals, including us, and are the creatures that produce “gas”–belches and other embarrassing explosive releases from bodily orfices.)

Science writer Ed Yong says the Christensenellaceae bacteria might be a “keystone” species, “one that wields a disproportionate influence upon the world around it.” He quotes the paper’s senior author thus, “’I’d never heard of it before,’ says Ruth Ley, who led the study. ‘It illuminates this real problem in the field. We only talk about things that have names.’”

I hadn’t ever heard of the Christensenellaceae bacterial family either. Turns out it was only described in 2012. Microbiologists are calling it a bacterial family, but the fact is that to date only one member has been cultivated in the lab. It’s been named Christensenella minuta.

Slowing down weight gain in mice

And it was C. minuta that helped the researchers complete the final part of their experiment and made their findings even more persuasive. They devised a microbiome that included other microbes found in previous studies to be associated with human obesity. They augmented that microbiome with human C. minuta and put the new microbiome into lab mice who had no microbiomes of their own (these are called germ-free mice.) These mice gained weight, but more slowly than other germ-free mice that had been inoculated with an “obese” microbiome containing no C. minuta. The presence of this particular human bacterium apparently can slow down weight gain in mice.

Ley told Tracy Vence at The Scientist that they are now hunting for the specific gene variants that are associated with particular microbes “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.”

Needless to say, another plan is to try to discover whether Christensenellaceae can be developed as a probiotic that could be useful for treating—or maybe even preventing—obesity. Ley told Elizabeth Pennisi at Science that they need to investigate whether the utility of such a probiotic might depend on whether the human host possessed the right genes for making the microbe feel at home.

Tabitha M. Powledge is a long-time science journalist and a contributing columnist for the Genetic Literacy Project. She also writes On Science Blogs for the PLOS Blogs Network. Follow her @tamfecit.

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