The Second Genome

 

 

Our bodies are alive – not just with muscles and nerves but with populations of bacteria and other single-celled organisms that are along for the ride. An estimated 10¹⁶ single-celled organisms – ten to a hundred times more than our own body’s cells – reside in each and every one of us. In recent years, we have been coming to understand the significance of these microorganisms – both for the healthy functioning of our bodies as well as for the role they play in such diseases as diabetes, obesity and cancer. If researchers once saw these organisms as “stowaways” that had a limited effect, mainly on the digestive system, today they are understood to be an integral part of who we are. Some even relate to the multicellular host and its population of single-celled organisms as a “super organism” with two genomes, the “second genome” being the combined genetic material of the microorganism population, which is a hundred to a thousand times larger than the “first genome.”

Dr. Eran Elinav, a medical doctor and researcher who recently joined the Institute’s Immunology Department, researches the complicated relationship between the host’s body and the population of microorganisms that call it home. In a series of papers published during his postdoctoral research, Elinav discovered a means of communication for passing messages between different cell types, in the process revealing clues as to how the single-celled population contributes to some of the most common diseases in the Western world: diabetes, cancer, arteriosclerosis and inflammatory bowel disease (IBD).
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The intimate relationship between microorganisms and their host transpires in a number of places, including the skin and such mucus membranes as the mouth and airways. The most dramatic encounters take place in the digestive system; the population density in the gut is one of the highest on the planet. And yet only the single layer of cells lining the gut – the epithelial cells – keeps the inner parts of our body free from this immense microbial population. In a study that appeared in Cell, Elinav found that this layer, which serves as the gut’s first line of defense against unwanted invaders, contains a sort of “snooping device” that helps the immune system keep tabs on the nearby bacteria. The sensor he discovered, called an inflammasome, is one of a group of factors identified in recent years that enable host and bacterial cells to communicate. (Related sensing systems – toll-like receptors – discovered in 1996, were the subject of the 2011 Nobel Prize in Medicine.) When Elinav disrupted the function of this inflammasome in mice, they developed inflammatory bowel disease, thus demonstrating the importance of this factor in keeping the gut healthy.

In further research, Elinav found that this inflammasome may also be involved in metabolic disease and cancer. In one study, which appeared in Nature, he created mice lacking the inflammasome in order to investigate a question about the progression of fatty liver disease: Why does this disorder, which affects up to 30% of the human population in the developed world, cause severe problems in only a minority of them? Most people with the disease do not suffer any serious problems, but around 20-30% progress to complications that include chronic liver inflammation, cirrhosis, tumors and even death. Elinav showed that a change in the composition of single-celled organisms in the gut can act as a “switch” that turns on the complications, and that such changes in the bacterial population may also be implicated in diabetes and obesity. Amazingly, in these instances, metabolic disease and obesity may be transferrable between individuals just by a transfer of these microbes between them. In additional research, he revealed a connection between these microbial changes and the propensity to develop cancer.