Brian Jones and Julian Marchesi, of University College Cork in Ireland, take a closer look at the genetic swap shops in our midst

When most people think about their gut, it usually means they are hungry, sated or feeling unwell. Very few of us would pause to consider what else may be going on in there and would only ever associate microbes with the gut in a negative sense, focusing on the pathogens that cause various gastro-intestinal (GI) upsets. However, for the majority of our lives, our guts are home to myriad micro-organisms that co-exist with us and even play crucial roles in our development and wellbeing. 

The human gastrointestinal tract is home to up to 1000 different species of bacteria and populations can reach 100 trillion cells in the large intestine. Collectively, these microbial passengers are referred to as the gut microbiota and form a highly complex ecosystem within the human GI tract. This community begins to develop shortly after birth and is involved in shaping our development from our earliest days. 

Over time, the gut microbiota has co-evolved with humans, resulting in a microbial community that performs many beneficial functions for the host. These include preventing our colonisation by pathogens, extracting nutrients from the food we eat, controlling cell division in the intestinal epithelium and developing our immune system. However, studies have also highlighted that gut microbiota contribute to diseases such as colorectal cancer and inflammatory bowel disease.

The microbial community's significance in human development and its impact on host health, means understanding the ecosystem's activities and capabilities should facilitate enhancements in human health and disease prevention, especially when coupled with data regarding the host genome. Unfortunately, analysing this activity is not easy. Of the plethora of bacterial species residing in our guts, we can grow relatively few in the laboratory. So, instead, we use powerful culture-independent approaches in which the individual genomes of the population are treated as one collective genome, broken into smaller pieces and transferred into bacteria that we can easily grow in the lab. This collective genome is referred to as the metagenome.

For most of our lives the composition of our microbiota is stable and so are the functions it performs. However, the composition can vary between individuals and so too could the relative outputs from these different communities. This difference makes the gut microbiota an important source of variation between individuals and potentially affects risk factors for numerous diseases. Ultimately, differences in our gut microbes may serve to increase the risk of certain diseases for some people while reducing it for others. 

Further variation can be introduced by bacteria being able to swap genes amongst themselves, allowing them to acquire new abilities. This process is called horizontal gene transfer (HGT) and is a major driving force in bacterial evolution and adaptation. HGT is mediated by mobile pieces of DNA, which are like hitchhikers that grab a ride with a bacterial host and use its cellular machinery to replicate. In return, these mobile genetic elements (MGE) often encode genes that are lacking in the host bacterium, but which provide it with a survival advantage such as antibiotic resistance.

MGE can also pick up genes from a host bacterium and then carry these with them when they move. This promiscuity promotes gene flow within bacterial populations, and allows genes to move into an established population from bacteria that are just passing through. In the human gut, HGT could introduce new functions to the bacterial community and is likely to be important in its adaptability to changes in the gut environment.

So, if human and bacterial co-evolution has selected for a microbiota adapted to life in the gut, and in an intimate symbiotic relationship with the human host, the pool of genes in the microbiota has likely been shaped to reflect this. By looking at the gene pool - the mobile metagenome - we are likely to identify important functions of the gut microbiota. It may also lead to strategies for manipulating these functions and, considering the link between the microbiota and human health, could have important implications for disease treatment.

Read Jones and Marchesi's highlight 'Accessing the mobile metagenome of the human gut microbiota' in issue 11 of Molecular BioSystems.