Researchers from ETH Zurich, the University Hospital of Bern and the University of Bern have equipped intestinal bacteria with data logger functionality as a way to monitor which genes are active in the bacteria. These microorganisms could one day offer a non-invasive tool for diagnosing disease or assessing the health effects of diet.
The intestines are home to countless bacteria that help us digest food. But what exactly do microorganisms do in the body? Which enzymes do they produce and when? And how do bacteria metabolize health-promoting foods that help us avoid disease?
To get answers to such questions, researchers from the Department of Biosystem Sciences and Engineering at ETH Zurich in Basel have modified the bacteria to act as data loggers for information on genetic activity. Together with scientists from the University Hospital of Bern and the University of Bern, they have already tested these bacteria in mice. This is an important step towards the use of sensory bacteria in medicine in the future for applications such as diagnosing malnutrition and understanding which diets are good for the individual.
The immune system becomes a data logger
The data logging function has been developed over the last few years by researchers led by Randall Platt, Professor of Biological Engineering at ETH Zurich. To do this, they used the CRISPR-Cas mechanism, which is a species immune system present naturally in many types of bacteria. If bacteria are attacked by viruses, they may include fragments of viral DNA or RNA in a part of their own genome called the CRISPR array. This allows bacteria to “remember” the viruses they have come in contact with, allowing them to fight a future virus attack at a faster rate.
To use this mechanism as a data logger, the researchers did not focus on DNA fragments of viral intruders, but focused on something else: the mechanism could be used to allow bacteria to incorporate fragments of their own information RNA (mRNA) into the array. CRISPR. MRNA molecules are the scheme that cells use to produce proteins. As such, mRNA fragments can reveal which genes are used to build proteins to perform cellular functions.
To make the method effective, scientists have introduced the CRISPR array of bacterial species Fusicatenibacter saccharivorans in a strain of the intestinal bacterium Escherichia coli, which is considered safe in humans and is available as a probiotic. The transfer involved a scheme of an enzyme called reverse transcriptase, which is able to transcribe RNA into DNA. This enzyme also transcribes information into mRNA in the form of DNA, which together with the accompanying CRISPR-linked proteins is required for inclusion of the DNA fragment in the CRISPR array.
Receive information without disturbing the body
Researchers at the University Hospital of Bern and the University of Bern, led by Andrew McPherson, then applied these modified intestinal bacteria to mice in the laboratory. They collected faecal samples from the animals and isolated the bacterial DNA, which they then analyzed using high-throughput DNA sequencing. With subsequent bioinformatics evaluation performed and evaluated in collaboration, they were able to work on the mass of data and reconstruct the genetic information of mRNA fragments. This has allowed scientists to determine with non-invasive means how often intestinal bacteria produce a mRNA molecule during their time in the body and thus which genes are active.
“This new method allows us to receive information directly from the gut without having to disrupt intestinal function,” said Andrew McPherson, professor and director of gastroenterology at the University Hospital in Bern. As such, the method has great advantages over endoscopy, which can be unpleasant for patients and is always associated with impaired intestinal function, as the examination requires that the bowels be empty.
Determination of nutritional status
“Bacteria are very good at registering environmental conditions and adapting their metabolism to new circumstances, such as changes in diet, “says McPherson. In experiments with mice given different foods, the researchers were able to show how bacteria adapted their metabolism to the corresponding supply of nutrients. was published in the latest issue of the magazine science.
Researchers would like to further develop the method so that one day they can examine human patients to see how diet affects the intestinal ecosystem and how it affects health. In the future, they hope to use the method to determine the nutritional status of children or adults. Armed with this information, doctors will be able to diagnose malnutrition or decide if a patient needs nutritional supplements.
In addition, the researchers were able to identify inflammatory reactions in the gut. The researchers applied the sensory bacteria to mice with intestinal inflammation, as well as to healthy mice. In this way, they could identify the specific mRNA profile of intestinal bacteria which go into inflammation.
Distinguish between different bacteria
The current study, published in the journal science includes research that allows researchers to distinguish two strains of bacteria from each other based on individual genetic “barcodes”. In the future, this will make it possible to study the function of gene mutations in bacteria in laboratory animals. This will allow scientists to compare the mRNA profile of different bacteria, such as normal versus mutant bacteria. Thanks to the molecular data logger, it is possible to determine this profile for the first time, as they pass through the gut not only when bacteria reach the feces, so the information shows what happened when the bacteria were still living in the gut.
Another possible way would be the further development of the system for distinguishing the RNA profiles of bacteria in the small and large intestines. In addition, the data logging feature can be included in other types of bacteria. This would open the door for applications in environmental monitoring. Analysis of soil bacteria from the seed field, for example, would determine whether herbicides have been used.
Possible safe application
Researchers have applied for a patent for the method itself and for the characteristic RNA profiles that are signatures of certain food molecules and indicators of intestinal health.
Before sensory bacteria can be used outside the laboratory – including in humans – scientists still need to clarify various safety and legal issues because the bacteria are genetically modified. “There are generally ways to use live genetically modified microorganisms as diagnostic or therapeutic agents in medicine, provided certain conditions are met,” explains Platt. It is possible, for example, to modify sensory bacteria so that they need certain nutrients and therefore survive only in the patient’s intestines. As soon as these specific bacteria leave the intestines, they will die. The integration of appropriate safety mechanisms is the next step towards the application of the method in medicine.
Florian Schmidt et al, Non-invasive assessment of intestinal function using sentinel transcriptional recording cells, science (2022). DOI: 10.1126 / science.abm6038. www.science.org/doi/10.1126/science.abm6038
Quote: Bacteria with a recording function capture intestinal health (2022, 12 May), extracted on 13 May 2022 from https://phys.org/news/2022-05-bacteria-function-capture-gut- health.html
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