Our microbiota is home to billions of bacteria that help us digest food, but not only. So what exactly do microorganisms do inside the body? What enzymes do they produce and when? And how do bacteria metabolize healthy foods that help us prevent disease?
Hijack the CRISPR-Cas mechanism of bacteria: To begin to answer these questions, the Basel researchers have modified bacteria in such a way that they function as data loggers and can tell them about gene activity. To make these modifications, the scientists used the CRISPR-Cas mechanism, which occurs naturally and is present in many bacterial species. If bacteria are attacked by viruses, this mechanism allows them to incorporate viral DNA or RNA fragments into a section of their own genome. This allows the bacteria to “remember” the viruses they have come into contact with, allowing them to fight off a future viral attack more quickly.
To use this mechanism as a data logger, the researchers exploited this mechanism so that the bacteria incorporate extracts of their own messenger RNA (mRNA), these mRNA molecules being the template cells use to produce proteins. These mRNA extracts can thus reveal which genes are active in encoding proteins necessary for the execution of cellular functions. Specifically, the researchers introduced the “CRISPR” mechanism of the bacterial species Fusicatenibacter saccharivorans into a strain of the intestinal bacterium Escherichia coli, considered safe in humans and available as a probiotic. The transfer included the design of an enzyme called reverse transcriptase, which can transcribe RNA into DNA.
A live rehearsal: The researchers then administered these modified gut bacteria to mice, collected and analyzed fecal samples, isolated the bacterial DNA, and were able to reconstruct the genetic information from the mRNA extracts. This has allowed scientists to noninvasively determine how often gut bacteria produce a given mRNA molecule while in the body, and therefore, in practice, which genes are active.
Get information without disturbing the body: “the technology allows to obtain information directly from the intestine, without disturbing the intestinal functions”, sums up Andrew Macpherson, Professor of Gastroenterology at Bern University Hospital. With great advantages over endoscopies, which interrupt intestinal function, since the intestines must be empty for the examination.
The implications They are many :
- understand the effects of a change in diet: bacteria are very good at registering environmental conditions and adapting their metabolism to new circumstances, such as changes in diet. Thus, experiments in mice given different foods illustrate how bacteria adapt their metabolism to nutrient supply;
- measure the effects of supplementation;
- understand how a food or diet influences the intestinal ecosystem and how this affects health;
- clarify the nutritional status and diagnose malnutrition;
- ultimately recognizing inflammatory responses in the gut or even diagnosing IBD.