The gut microbiota, the ecosystem of bacteria that lives inside the human gastrointestinal tract, has been recently shown to release chemical signals that can make alterations to our genes. Research conducted at the Babraham Institute near Cambridge demonstrated that certain bacteria among the microbiota release molecules called short-chain fatty acids (SCFAs). These acids were able to modify gene activity by affecting crotonylations, the chemical markers attached to our genome.
The relationship between our bacteria and our body has been well-documented. This ecosystem, which contains more cells than the human body, can affect everything from our allergic responses to our mental health. Study of the microbiota has even begun to yield therapeutic uses for these bacteria, through faecal transplants, which may take up an important role in stratified medicine. The genetic effects of the microbiota are less well studied, but the relationship between our genes and our germs could be of great importance to modern medicine.
Hydra to Humans: Gut Bacteria at all Levels of Life
The microbiota forms soon after birth (although some studies suggest even earlier origins), and our environment is the most important factor is determining what species of bacteria grow inside us and in what number. Genetics, however, do have some influence. This effect can be seen at all levels of animal life. Research using simple animals such as Hydra, (a freshwater-dwelling organism that is most commonly studied for its apparent inability to die) has suggested that species similarity can trump even strictly enforced environmental factors in determining biota composition1.
In more complex animals, the influence of genetic factors can still be seen. A recent study by scientists at UCLA examined microbiota composition in mice, and found that the heritability (the proportion of variation related to genetics) of many of the strains found in the microbiota was variable, ranging between 26% and 65% heritability2.
Heritability studies in humans have proved divisive. Twin studies are an important tool for studying genetic influence in people. These compare monozygotic (identical) or dizygotic (non-identical) twin pairings to allow researchers to rule out environmental impacts on a given factor, such as microbiota, as much as possible, allowing purely genetic influence to be analysed. The results from these studies have often been lacking in the appropriate statistical power to tease out any meaningful gene-microbiota relationship3,4. A much larger study, led by Professor Ruth Ley, then at Cornell University, aimed to clarify the matter by using a high-powered study involving over 1000 faecal samples5. The resulting data identified the same variable heritability of individual bacterial species. The bacteria that had the highest heritability, Christensenella minuta, was examined in more detail. It was noticed that this family was enriched in individuals with low body mass.
The authors hypothesised that C. minuta could be influencing BMI through impact on its host’s metabolism. They took a microbiome of bacteria that was associated with obesity and added it to the guts of germ-free mice, who lack a natural microbiome. In some mice, this microbiome was then supplemented with C. minuta. These mice gained less weight in response to heavy eating than C. minuta-free mice, suggesting these bacteria could indeed have an effect on host metabolism. Interestingly, C. minuta also produces SCFAs, that same molecule which was shown to cause genetic modifications in the Babraham study. Does C. minuta impact BMI through SCFA modifications? Does this highly heritable bacterium have more widespread impacts that have yet to be uncovered? This all remains unclear. The fact remains that all this science is very new - C. minuta was only discovered in 2012, after all.
What is clear is that the relationship between the bacteria we host and the cells of our body is far closer and more reciprocal than previously thought. If future medical treatments want to create personalized medicine - custom treatments for each patient that consider genotype as well as phenotype - then the contribution from each individual’s microbiota should not be ignored.
1. Fraune, S., & Bosch, T. C. (2007). Long-term maintenance of species-specific bacterial microbiota in the basal metazoan Hydra. Proceedings of the National Academy of Sciences, 104(32), 13146-13151.
2. Org, E., Parks, B. W., Joo, J. W. J., Emert, B., Schwartzman, W., Kang, E. Y., ... & Drake, T. A. (2015). Genetic and environmental control of host-gut microbiota interactions. Genome research, 25(10), 1558-1569.
3. Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., ... & Egholm, M. (2009). A core gut microbiome in obese and lean twins. nature, 457(7228), 480-484
4. Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., ... & Heath, A. C. (2012). Human gut microbiome viewed across age and geography. Nature, 486(7402), 222-227.
5. Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Koren, O., Blekhman, R., ... & Spector, T. D. (2014). Human genetics shape the gut microbiome. Cell, 159(4), 789-799.