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   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    
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   WIKIMEDIA COMMONS, TWINSUK    
   Previous 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 Chris   
   ensenellaceae--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.    
      
   Tags    
   twins, microbiome, human microbiome, gut microbiota and genetics & genomics    
      
      
      
      
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