Saturday, November 8, 2014

Firmicutes for a slimmer waist?

Obesity is a complex metabolic disorder. Both genetic and environmental factors play a role. More recently, third component, gut microbiota was implicated as well.

Several seminal studies from Jeffrey Gordon's lab suggested that abundance of bacterial family of Firmicutes in the human gut flora contributed to obesity due to their efficacy in harvesting energy from the food source.   

However, new study in journal Cell, surprisingly points to opposite direction. This study led by Ruth Ley (US), in collaboration with Timothy Spector (UK), has examined a stability of human gut microbial community across genetically related (twins) or unrelated human population. 

Twins are ideal to study Nature (Darwinian genetics) versus Nurture (Lamarckian epigenetics) effects. Initial studies on twins indicated that environment (food, habits, etc), rather than genes played more fundamental role in altering gut flora composition. However, it seems those prior studies have used smaller sample size. In this study, however, the authors have used larger pool size of twins (416 twins) for comparison and for validation of their observation.

First, the authors found that gut flora was less variable between monozygotic twins, as compared to dizygotic twins or unrelated individuals. This suggests that genes play a more dominant role in influencing gut microbiota.

Interestingly, gene effect was significant for bacterial family of Firmicutes

However, surprisingly, no significant difference were found for bacterial family of bacteroidaceae between twins or unrelated individuals.

Second, the authors found that between monozygotic twins, the most heritable bacterial family was Christensenellaceae. This is a newly described bacterial family.

Christensenellaceae belong to Firmicutes family.

Interestingly, the authors made observation that abundance of Christensenellaceae in the gut flora correlated with low BMI (<25). Indeed, fecal transfer experiment in germ-free mice showed that weight gain was inversely correlated with the level of Christensenellaceae in donor stool. The authors also made an observation, that for some unknown reason, Christensenellaceae effect on BMI was most prominent when Christensenellaceae was associated with metanogenic bacteria.   

Finally, to validate their observation, the authors added live Christensenella minuta to fecal transplant from obese individual with no detectable level of Christensenellaceae and transferred into germ-free mice. At day 21 post transfer, mice with live Christensenella minuta gained less weight and had less adipose tissue.

In summary, the results from study indicate that genetic factors may play a dominant factor in determining the presence of some but not all bacterial communities in the gut. In addition, the data indicate that few bacteria species play disproportionately large role in influencing low BMI. The most intriguing observation of this study is the fact that presence of bacteria from Firmicutes family correlated with low BMI.

David Usharauli    


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