INTESTINAL HEALTH: Bacteria equipped to track data?

INTESTINAL HEALTH: Bacteria equipped to track data?

Our microbiota hosts 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 ward off 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 fragments of viral DNA or RNA 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 bacteria incorporate extracts of their own messenger RNA (mRNA), with these mRNA molecules being the template cells use to make proteins. These mRNA extracts can thus reveal which genes are active in coding for 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 intestinal bacteria Escherichia coli, considered safe in humans and available as a probiotic. The transfer included the blueprint for an enzyme called reverse transcriptase, which can transcribe RNA into DNA.

An in vivo test: 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 determine by non-invasive means how often gut bacteria make a given mRNA molecule while in the body, and therefore in practice which genes are active.

Obtain information without disturbing the body: “the technology makes it possible to obtain information directly from the intestine, without disturbing the intestinal functions”, sums up Andrew Macpherson, Professor of Gastroenterology at the University Hospital of Bern. With major advantages over endoscopies, which disrupt bowel function, since the bowels must be empty for the examination.

The implications 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 dietary changes. Thus, experiments on 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 dietary status and diagnose malnutrition;
  • finally, recognizing inflammatory responses in the gut, or even diagnosing IBD.

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