Gut bacteria are crucial to human health, but researchers have long struggled to cultivate many of these microbes in the laboratory to study and understand them better. A novel method is being used to address this challenge.
Some bacteria promote health and others harm health. The overall interaction of these bacteria can affect the risk of developing cardiovascular disease, diabetes or Alzheimer’s disease and of having overweight.
Researchers have long strived to understand the role of each type of bacteria, but many are difficult to study because cultivating them in the laboratory is not easy.
This problem has now been solved using a new method that enables researchers to grow relevant bacteria in a stool sample and study their effects in detail.
“The challenge is that many gut bacteria are difficult to cultivate because they cannot grow on traditional growth media, and this creates difficulty in identifying new bacteria to be included in probiotics. We need a method to selectively grow specific bacteria, and we developed this,” explains a researcher involved in developing the method, Morten Otto Alexander Sommer, Professor, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.
The method has been published in Nature Communications.
Whole-metagenome sequencing of stool samples
Researchers identifying gut bacteria typically perform whole-metagenome sequencing on the total DNA present in a stool sample. This provides insight into the genes within the intestines and, consequently, which bacteria are present.
For example, certain gut bacteria can produce dopamine. To determine whether these bacteria are present in an individual’s gut, researchers can search for the genes that cause dopamine production in a stool sample.
Now, imagine that the genes are detected, but only one in a million bacteria in the sample produces dopamine. This makes isolating the specific bacterium for detailed study incredibly challenging.
“If only a few bacteria of a specific type are present in the gut, identifying the ones of interest requires screening a vast number. This problem would not arise if one in 100 or one in 10 bacteria were relevant,” says Morten Otto Alexander Sommer.
Preferential cultivation of bacteria
The method the researchers developed enables specific bacteria to be cultivated from stool samples.
The challenge is that different bacteria require distinct conditions to grow. For instance, some thrive in an acidic environment, whereas others thrive in an alkaline one. Certain bacteria require additional amounts of specific types of sugar, whereas others use different types of nutrients.
The method cultivates the target bacteria by exposing the stool sample to various conditions that favour their growth.
This involves initially investigating how specific types of sugar, lactic acid, protein or even substances such as drugs or caffeine influence the concentration of the desired bacteria.
Researchers can then analyse this by resequencing the total DNA present in the sample and determining the proportion that contains genes specific to the bacteria of interest.
For example, if mucin and caffeine are each found to increase the proportion of a specific type of bacteria in a stool sample, combining the two substances can further promote its growth.
The effects of adjusting the levels of substances that provide optimal growth conditions for the desired bacteria can also be explored.
“This method enables us to isolate the bacteria we want to study. We can potentially increase their presence from one in a million to one in 100. This makes it 10,000 times easier to isolate the bacteria – and perhaps one million times easier than growing them in a standard medium,” explains Morten Otto Alexander Sommer.
Identifying next-generation probiotics
Morten Otto Alexander Sommer explains that the method is primarily intended for research and for studying individual bacteria that have been challenging to analyse.
He also envisions potentially using it in better identifying and cultivating bacteria of interest for probiotics: promoting health through bacteria.
In addition, the discoveries could extend to bacteria researchers aim to eliminate, aiding in developing targeted medicines.
“This method enables us to explore gut bacteria and uncover the effects of those we previously could not cultivate meaningfully. There is now significant interest in the approach we have developed,” concludes Morten Otto Alexander Sommer.
