Twin study shows genes influence gut micro biome
is known to be influenced by a person’s diet
and environment. Now, a study of twins
shows that genetics can also provide an edge
in the microbial battle. Researchers identi-
fied a microbe that appears to keep waist-
lines trim—and found that genes influence
its abundance. “It’s the first really strong evidence that human gut microbiology is
genetically controlled,” says geneticist Oluf
Pedersen of the University of Copenhagen,
who wasn’t involved in the study.
The work, published in the 6 November issue of Cell, raises hopes for microbial treat- ments for obesity. But microbial ecologist Ruth Ley of Cornell University and her col- leagues originally wanted to answer a more basic question: Do genes affect the makeup of the gut microbiome? Like many research- ers trying to distinguish environmental from inherited influences, they turned to twins. Working with colleagues running a large-scale project called TwinsUK, the team collected more than 1000 stool sam- ples from 171 identical and 245 fraternal pairs of twins, as well as 173 samples from unrelated individuals. Among these people,322 were overweight and 183 were obese. Previous twin studies had failed to identify a genetic connection to microbiome diver- sity and abundance, but those studies looked at the microbiome as a whole. The new study instead takes a species-by-species approach. By sequencing and analyzing DNA from the fecal samples, Cornell graduate student Julia Goodrich and her colleagues found more than 9600 genetically distinct micro- bial “species.” Most microbes varied accord- ing to environmental factors, but some were apparently influenced by genetics, because they were more similar in identical twins than in fraternal twins. The genetic makeup of these twins may affect gut physiology or biochemistry in a way that favors the growth of some microbes over others, the researchers suggest.
Gut microbes are soldiers in the battle
of the bulge, researchers have learned in the past few years, with some or- ganisms seeming to promote thin- ness and others triggering weight gain. The makeup of such microbes
of the bulge, researchers have learned in the past few years, with some or- ganisms seeming to promote thin- ness and others triggering weight gain. The makeup of such microbes
The work, published in the 6 November issue of Cell, raises hopes for microbial treat- ments for obesity. But microbial ecologist Ruth Ley of Cornell University and her col- leagues originally wanted to answer a more basic question: Do genes affect the makeup of the gut microbiome? Like many research- ers trying to distinguish environmental from inherited influences, they turned to twins. Working with colleagues running a large-scale project called TwinsUK, the team collected more than 1000 stool sam- ples from 171 identical and 245 fraternal pairs of twins, as well as 173 samples from unrelated individuals. Among these people,322 were overweight and 183 were obese. Previous twin studies had failed to identify a genetic connection to microbiome diver- sity and abundance, but those studies looked at the microbiome as a whole. The new study instead takes a species-by-species approach. By sequencing and analyzing DNA from the fecal samples, Cornell graduate student Julia Goodrich and her colleagues found more than 9600 genetically distinct micro- bial “species.” Most microbes varied accord- ing to environmental factors, but some were apparently influenced by genetics, because they were more similar in identical twins than in fraternal twins. The genetic makeup of these twins may affect gut physiology or biochemistry in a way that favors the growth of some microbes over others, the researchers suggest.
The microbes most strongly
affected by genes belong to a
recently discovered, rather
obscure family of bacteria
called Christensenellaceae. To
the researchers’ surprise, this
family was most abundant in
lean twins and rare in obese
ones. To see how the microbes
might influence weight, Ley
and her team transferred fecal
material from lean and obese
twins into germ-free mice.
The weight gain in the mice
mirrored that of the humans
donating the feces. And when Goodrich
supplemented feces from obese twins with
one of the microbes, Christensenella minuta,
and gave them to mice, the mice stayed lean.
The microbe “has some aspect of being able
to influence weight,” says Cornell geneticist and co-author Andrew Clark.
“We want to see if [the microbe] can be developed as a probiotic for helping people maintain their weight once they’ve lost it,” Ley says. But she and her colleagues first need to figure out how C. minuta exerts its effects and whether such a treatment would work only in people genetically dis- posed to supporting it. At this point, says Nita Salzman, a pathologist at the Medi- cal College of Wisconsin in Milwaukee, to think about a probiotic “is almost certainly an oversimplification.” ■
“We want to see if [the microbe] can be developed as a probiotic for helping people maintain their weight once they’ve lost it,” Ley says. But she and her colleagues first need to figure out how C. minuta exerts its effects and whether such a treatment would work only in people genetically dis- posed to supporting it. At this point, says Nita Salzman, a pathologist at the Medi- cal College of Wisconsin in Milwaukee, to think about a probiotic “is almost certainly an oversimplification.” ■
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