Human genetics and human gut microbiota

Obesity is taking America and many other Westernized countries by storm.  According to the Center for Disease Control (CDC), over one-third of Americans struggle with this disease today. Obesity is a complex disorder that can lead to many health problems, including heart disease, diabetes and certain cancers. In a new study released on November 6 of 2014, researchers provide new insight into what could cause obesity besides factors such as lifestyle and diet. Perhaps not surprisingly, this “new” factor is encoded in a person’s genetic makeup.

What is even more striking, however, is what our genes encode. Ruth Ley of Cornell University and her colleagues discovered that a large amount of bacteria in a person’s gut is “inherited” in relationship to their genotype, or genetic information. Furthermore, they discovered that a particular group of bacteria in the family Christensenellaceae is the most heritable, and happens to relate to a lean body mass index (BMI). This surprising finding may provide insights into why some people struggle with weight gain while others on a similar diet do not.

The relationship between BMI and overall health has been well known for some time. BMI calculates a number based on height and weight, directly correlating with body fat content as well. High BMI values associated with obesity clearly track with cardiovascular disease and other maladies, which are significant causes of mortality in the U.S. and other Western nations.

The simplest explanation for obesity is that when people eat more calories than they burn, they store excess energy as fat, thus increasing their BMI. This idea may be too simple, however, as there are many factors that may enhance or lead to obesity such as environment, food quality and genetics—or what’s living in your gut.

To test the idea that a person’s gut bacteria composition—or microbiome—is heritable, the Cornell researchers conducted a twin study. Twin studies take advantage of the fact that identical twins share 100 percent of their genes, whereas fraternal twins typically share only about 50 percent of their genes. (Other factors, though, are roughly equal for both types of twins if they are raised in the same environment.) As such, a greater similarity between identical twins than between fraternal twins implies that genetics play an important role in the process being studied.

After collecting more than 1,000 fecal samples from 416 identical and fraternal twin pairs, Ley and colleagues were able to determine that the bacteria present in their subjects’ guts showed significantly more similarity between identical twins than fraternal twins. The researchers established this finding using a method called “genetic barcoding,” in which small segments of DNA that vary between bacterial species are sequenced to reveal the type and abundance of microorganisms present in each sample. From this list of species, it was determined that several species of gut bacteria—Christensenellaceae being the most prominent—seem to be “inherited” in a genetic fashion.

Remarkably, the abundance of bacteria also correlated with BMI of the various twins. To demonstrate that this microbial difference actually influences BMI, the researchers injected human fecal samples from lean and obese individuals into the guts of germ-free mice. Mice injected with fecal samples from lean subjects with higher Christensenellaceae levels showed less weight gain compared to those injected with obese fecal samples. This result was reversible, as mice receiving the obese fecal sample could be induced to lose weight when given a sample rich in Christensenellaceae.

Together these findings suggest a strong link between genetics, gut microbiome and BMI, indicating that the old maxim “you are what you eat” may not be quite as true as was once suspected.