Up to two kilos of our body weight is made up of bacteria - which means they must be doing us some good - even as we indulge over the festive season, writes Dick Ahlstrom
CONSIDER, AS you prepare to tuck into your forthcoming Christmas feast, that your food would be doing very little for you were it not for your personal team of little helpers who allow you digest your food. The turkey and sprouts, pudding and mince pies would give you next to nothing were it not for these unsung heroes.
We are referring of course to the bacteria that occupy your gastrointestinal (GI) tract, all 100billion of them. Between 500 and 1,000 species occupy this space, and account for about 2kg of a typical adult's body weight. They help digest your food but now also offer a possible treasure-trove of new drugs, anti-viral and anti-microbial agents suited to new medical treatments.
Discovering this hidden potential is the research agenda set by Dr Cormac Gahan of University College Cork's department of microbiology. Substances produced by these organisms could be hugely important for human health, he suggests.
He joined colleagues from UCC's school of pharmacy and the alimentary pharmabiotic centre in a recent study that was published in the US Proceedings of the National Academy of Sciences. It included Prof Colin Hill and Julian Marchesi from the APC and Dr Máire Begley and Dr Brian Jones from Gahan's own labs. "It is all about the use of functional metagenomics to interrogate the community of organisms (in the gut) that might be difficult or impossible to culture in the lab," Gahan explains.
The traditional approach used in studying these organisms assumed that a whole bacterium was needed so it could be cultured in the lab and then its entire genome sequenced, Gahan says.
The team used a different approach known as "metagenomics" a relatively new approach that can look at genes from many organisms at once. Metagenomics is different in that it allows the researcher to recover bits and pieces of different bacterial genomes directly from a single complex environment such as the GI tract.
It is particularly valuable when trying to understand the function of specific genes and the proteins they produce, he says. His PNAS paper was about this very approach, trying to understand how the huge community of GI bacteria could survive in such a harsh environment.
It looked in particular at bacterial ability to survive in the "bile salts" that arise in the stomach. These help in the digestion of fats, but are very harsh and it is remarkable that bacteria have evolved that can live readily in this toxic environment.
Not one or two but all of the various bacteria in the GI tract are able to survive bile salts because they release a "hydrolase" that protects them, Gahan says. "We figured that a lot of these organisms will be expressing bile salt hydrolase. We figured if this was a widespread factor then it was important for survival. It was widespread in the microbial community."
Metagenomics is ideal for looking at a shared function or characteristic. It allows a mishmash of DNA to be recovered, typically in pieces of about 40,000 steps or "base pairs", each of which will carry about 40 genes, he explains.
If the bacteria have the genes to survive bile salts, these genes will be very similar if not identical, regardless of which species they come from. "It doesn't really matter what species it comes from, it was more to get at this function. Sequencing alone would pick the genes up but you wouldn't have what the function was," he says.
The DNA to produce bile salt hydrolase was readily visible using metagenomics, showing that this was a function common to the bacterial community and clearly a part of their ability to survive. But how did they all come to have this, given it isn't something that would readily arise until the bacteria evolved to live in the gut?
It comes down to sharing. "We believe there is a lot of lateral gene transfer in the gut," Gahan says. The bacteria have ways of transferring and sharing genes across species - and once the bile salt hydrolase gene is taken up, that species can survive that challenge. "One of the key things is to understand how gut micro-organisms might be different to organisms outside this environment," Gahan suggests as a reason for studying this. But it is also about what else this vast microbial community might offer.