Scientist have mapped the genes of 500 previously unknown gut bacteria and more than 800 bacteriophages. This means that all intestinal bacteria are now mapped.
The total amount of genes in the gut flora is more than 100 times that of our own genome and most of those bacteria play an important role for health.
Many of the bacteria are essential for our immune system. Furthermore, recent research has shown how gut flora can influence the development of diseases and disorders such as ADHD, diabetes, and obesity.
The gene map can be used to strengthen our understanding of a long list of disorders and in the search for new types of antibiotics, says Associate Professor Henrik Bjørn Nielsen, who helped conduct the study at the Centre for Systems Biology at the Technical University of Denmark.
“Gut bacteria has been one of the hottest scientific topics in the past four years. Prior to our study, only around 10 percent of these bacteria were known. We have mapped the remaining 90 percent. This could lead to major medical progress in the future,” says Nielsen.
Allan Flyvbjerg, Dean of Health at Aarhus University, did not participate in the new study but is very excited about the results.
"Gut bacteria is a thrilling area of research. We have between 1.5 and 2 kilos of bacteria in our guts and all indications point to the fact that these are directly linked to our health and illnesses. This study provides an accurate picture of the kind of bacteria which live in the gut,” he says.
The study was recently published in Nature Biotechnology.
The possibilities created by the newly mapped bacterial genomes are huge.
By using the genomes, scientists could find out which bacteria are either present or missing in the gut of people with diseases such as type 2 diabetes, chronic, inflammatory bowel diseases, autism, ADHD, and schizophrenia -- or people who are severely obese.
New therapeutic treatments could become possible where bacteria are either removed or added to the gut in order to change the total gut flora and thereby creating a more healthy system.
"It’s already proven that you can take gut bacteria from a fat mouse and transfer it to a thin mouse. And then the thin mouse becomes fat," says Nielsen.
Flyvbjerg agrees that the study could pave the way for treating a variety of diseases through manipulation of the gut flora.
“In order to manipulate the gut flora as a means of treatment we needed to dig a little deeper into the understanding of the bacteria that live there. This, I feel we have come closer to understanding now,” he says.
The discovery could also be used to better understand how drugs are absorbed through the gut. When medication is orally consumed the gut bacteria is the first to encounter and digest the medicine.
This means that medicine is digested very differently from person to person depending on the bacterial composition in their gut.
We can now start to explore solutions for this, explains Nielsen:
Treatment using bacteriophages is already used today, among other places in Russia and Georgia.
The method was was already developed in the 1920s but never caught on outside the Soviet Union. The main reason being that the rest of the world decided to focus on antibiotics instead, for example penicillin.
As more and more bacteria are becoming resistant to antibiotics, scientists are now considering phage therapy as a possible form of treatment.
"We can begin to understand the interaction between bacteria and us in a more nuanced way. Since each of us seem to have different bacterial combinations in the gut we can start to consider whether we should also have varying amounts and types of medication to achieve the same desired goals or to avoid certain side effects,” he says.
The study also points to a new way of understanding antibiotics.
In the study, the scientists not only mapped different bacterial genomes. They have also mapped bacteriophages’ (viruses that infect bacteria) genomes.
In the process they discovered 800 new bacteriophages.
The scientists looked at which and how bacteriophages attack and destroy particular bacteria.
The experiment involved observing bacteria and bacteriophages activity over time. Specific bacteria and specific bacteriophages were placed together in a sample and the scientists could then watch how the bacteria disappeared over time.
By doing so it was possible to conclude which bacteriophages finish off which bacteria.
This type of antibiotics, known as phage therapy, could very well have a central role within future treatment.
"By using bacteriophages we’re focusing treatment, aiming directly towards one type of bacteria rather than shooting around aimlessly as one does today with antibiotics,” says Nielsen. “It’s much healthier for the gut flora and therefore also the body. Also, we get a new type of antibiotic with a lot of potential -- since bacteriophages are constantly evolving alongside bacteria, the therapy can be updated continuously as the bacteria become resistant.”
In order to discover the 500 remaining genomes, it was necessary for the scientists to smash up the total amount of DNA mass within the gut flora into millions of bits. This created a gigantic hotchpotch of DNA fragments which the scientists then needed to sort out. It corresponds to having to assemble thousands of puzzles, each with tens of thousands of pieces that are all mixed together in one big pile.
In this imagery the number of puzzle pieces translate to the genes in the bacterial genomes. However, unlike a puzzle, the genes do not only fit one puzzle but also many other games.
The scientists hypothesized that genes which originate from the same bacterial species, should exist in the same amounts -- e.g. if there’s 1,000 copies of one gene and 1,000 of a second gene then the different parts may originate from the same kind of bacteria.
The scientists retrieved intestinal bacteria from 400 Europeans. This meant they could observe whether or not the ratio between different parts showed the same pattern no matter the individuals’ particular compositions of intestinal bacteria.
In this way the scientists pieced together the bacteria bit by bit until they had collected the genomes of 741 bacteria -- of which approximately 250 were already known.
"We did not use any prior knowledge about known bacteria and bacteriophages in our analysis. We have simply shown how much information there was in the data [from the DNA]. It's beautiful science -- even if it is a little geeky,” says Nielsen.