G(ut)enetics: The Genetic Influence of Our Internal Symbionts

by Austin Valido

The human body is crowded. From the surface of our skin to the depths of our intestines, we are inundated with microscopic bacterium that aid with everything from defense to digestion. Large-scale scientific endeavors, headlined by the Human Microbiome project, have catalogued millions of species of bacteria and are just beginning to uncover the full impact of our most intimate neighbors. Within the human body is a diverse biological industry containing ten microbes for each human cell and 100 microbial genes for each unique human gene.1 The study of the microbiome has exploded in recent years and has started to cross disciplinary lines, creating a field of research that combines aspects of ecology, epidemiology, cellular biology, chemistry, and recently, human genetics. These interdisciplinary collaborations are working to answer the numerous exciting questions about the microbiome that remain unanswered. Recently, research has used population genomics to explore human genetics and the microbiome, searching for the answer to the central question of what, if anything, really controls our internal menagerie?

WHO CONTROLS WHOM: EMERGING RESEARCH ON MICROBIOME HERITABILITY

Researchers have now found a connection from the human genome to the gut microbiome: the Ley Lab at Cornell University recently conducted a twin heritability study which found a strong correlation between the presence of a single bacteria, C. minutia, and a genetic heritability for a low BMI score.2 The variability of the microbiome, from diet to a changing household environment, makes it difficult to differentiate between these various influences and prove causality for a genetic relationship. However, using the largest adult twin registry in the United Kingdom as a test population, the researchers were able to collect an enormous amount of data to analyze—78,938,079 quality filtered DNA sequences that mapped to certain species of bacteria.2 Incorporating the effects of both shared and unique environments in the analysis, the study illustrated that there was a correlation between host genetics and the content of the microbiome. Ley concludes, “Our results represent strong evidence that the abundances of specific members of the gut microbiota are influenced in part by the genetic makeup of the host.”2 The evidence was in the excrement—human genetics shape the gut microbiome.

This study develops a pathway in which phenotype is modified not through genetics but the symbioses within our gastrointestinal tract. Ley and her colleagues have uncovered a detour in the central dogma of biology. It seems our genome has evolved a way to influence phenotype—in this case metabolism—through the recruitment of a third party.

Further research has pushed this past the gut microbiome to a full body analysis. Mining data from the Human Microbiome Project, Ran Blekhman and colleagues have traced an association between genetic variation and 10 microbiome sites on the human body.3 Immunity-related pathways, including the hormone leptin, which modulates immune cells and is implicated in appetite and weight gain, seem to play an important role in microbiome control across the body.3 This research has exciting potential for translational effects, providing a possible new route to treat metabolic disorders through the analysis of the microbiome.

AN UNEXPECTED GIFT: TRANSMISSION OF MICROBIOTA

Past the important role of translational research, this developing understanding of our genetic control of the microbiome is remarkable when placed in the context of research being done on the human fetal microbiome. Important questions remain on how exactly the microbiome develops. The classic idea of a sterile birth seems to be under attack— collective observations raise the possibility that the infant may be first seeded in utero by a source such as the placenta.4 The early microbiome may begin long before an infant is introduced into the environment. Research into the relationship between genetics and the microbiome may be the first step in creating a fuller understanding of the development of the microbiome, such as deciding which bacteria are left to colonize from the mother/environment and which are purged by our immune system.

Together these studies are working to paint an image of the processes that coalesce to select, nurture, and utilize our internal bacterial symbionts. As we learn more about the biological and chemical controls our body implements to cull favorable symbiotic populations, it is important to think about the impact on medicine and human health. Can interventions be created that involve these genetic and maternal pathways to alleviate the burden of diseases such as diabetes and metabolic disorders? Only time can tell in a field boldly exploring the uncharted territory of human biology.

Austin Valido ’18 is a sophomore in Eliot House.

Works Cited

  1. Smillie, C. S., et al. Nature, 2011, 480.7376: 241-244.
  2. Ley, R. E. et al., Cell, 2014, 159.4: 789 – 799.
  3. Blekhman et al. Genome Biology, 2015, 16:191.
  4. Aagaard K. et al., 2014, Sci Transl Med 6.237: 1-10.

 

 

Categories: Fall 2015

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