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Longevity Briefs: Could We Use Gene Therapy On Our Gut Bacteria To Treat Disease?

Posted on 16 August 2022

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: We know that the gut microbiome can have a profound effect on long-term health, as the diversity and sizes of ‘good’ and ‘bad’ bacterial populations can influence the body’s metabolism, immune system and more. The size of these populations changes during ageing, and unfortunately these changes are always detrimental, with good bacteria becoming less diverse and declining in number. Probiotics can be beneficial, but generally don’t survive in the gut for very long. Faecal microbiota transplant – transplanting the stool from a person with a healthier microbiome – is currently the best way we have to improve the health of someone’s microbiome long-term. However, what if we could use genetic engineering to simply confer beneficial properties on someone’s native gut bacteria?

What did the researchers do: In this study, researchers isolated multiple strains of E.coli bacteria from young mice, then genetically modified these bacteria by introducing various beneficial genes. Examples of some of the genes introduced included the gene for interleukin 10 (IL-10), a molecule common to mammals that suppresses inflammation, and bile salt hydrolase (BHS), a molecule produced by some gut bacteria that indirectly affects the absorption of fats and the handling of sugar.

They then reintroduced these bacteria back into the guts of some of the mice when they were 12 weeks old, while other mice received a control treatment. They then monitored the mice to see how long the genetically altered bacteria survived, and whether they were able to confer any health benefits.

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes

Key takeaway(s) from this research: After only a single treatment, the altered bacteria persisted in the mice’s guts for the duration of their lives. Mice that received the modified bacteria didn’t eat any more or less than the control mice, but after 3 months, the treated mice had significantly lower blood sugar after feeding compared with the controls. When the researchers tried giving the same treatment to mice genetically predisposed to become obese and diabetic, they found that the treatment didn’t affect the mice’s weight, but it was associated with a significant improvement in blood sugar control.

Blood glucose (sugar) of mice following a meal 15 weeks after treatment with modified bacteria (orange line) or unmodified bacteria as a control (purple line).
Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes

Introducing new genes into bacteria native to the gut generally makes them less able to compete in the gut environment, but this study suggests that, at least in mice, certain modifications still allow native bacteria to survive throughout the animal’s entire lifespan. The researchers were also able to introduce similar genetic changes into human E.coli strains, though we don’t know how long these would persist if reintroduced into the human gut, nor do we know if they would have similar health benefits to what was observed in the mice.

Most probiotics don’t contain strains of bacteria that are native to the human gut, which is why they don’t tend to survive very long. ‘Domesticated’ strains are preferred over native strains because native strains are harder to culture and modify in the lab, though it is becoming easier with newer methods. This study suggests that using native bacteria to introduce beneficial genes may be worth exploring in humans, even if it is difficult.

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    Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes:

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