Longevity Briefs: Resetting The Gut Microbiota With Vat-Grown Bacteria

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.

The problem:

With advancing age, there’s a shift in the composition of the gut microbiota – the community of microorganisms that live inside the intestines. This shift correlates with the occurrence of age-related disease and is known as gut dysbiosis. While not proven in humans, mouse studies appear to show that transplanting the gut microbiota from a young mouse into an older mouse protects the older mouse against age-related disease and deterioration.

Currently, the only way to restore the gut microbiota to a younger state in humans – at least in a lasting way – is with a faecal microbiota transplant (FMT), aka a stool transplant. FMT has already been clinically approved for the treatment of C.difficile infections, but its use for general health would pose a few problems. Firstly, everyone’s gut microbiota has a different composition, so not everyone receiving FMT would be receiving the same treatment. This complicates both the study and the regulation of the therapy. Additionally, even if FMT were to prove safe and effective for the prevention of age-related diseases, it would be difficult to scale up to meet the demand – we would need many, many stool donors. For these reasons, we will ultimately need to be able to grow ‘artificial’, standardised microbiota products at an industrial scale. In this study, researchers take the first step towards this goal, and compare the effectiveness of their product against that of regular FMT for the treatment of C.difficile.

The discovery:

Researchers developed their treatment, referred to as MTC01, by selecting 15 strains of bacteria present in donor stool samples. These bacteria were then cultured in an anaerobic chamber. By restricting the therapy to just 15 strains (as opposed to the thousands usually found within the human gut) researchers could ensure that the product would be consistent and reproducible.

The researchers then ran a phase I randomised trial. 18 patients with recurrent C.difficile infection were randomised to receive either low or high-dose FMT, or low or high-dose MTC01. Both treatments were delivered via colonoscopy, though an oral formulation of MTC01 has since been developed. The researchers found that the number of adverse events were identical between the FMT and MTC01 recipients – 5 adverse events for each. Furthermore, 8 weeks after treatment, C.difficile recurrence was prevented in 8 out of 9 patients who received FMT, vs 7 out of 9 patients who received MTC01. Given the limited number of participants, this essentially means that MTC01 was not discernibly different from FMT in terms of safety or efficacy.

The implications:

This research provides some early evidence that lab-grown human bacteria might be a successful substitute for donor stool, at least in the treatment of C.difficile, although larger trials will be needed to confirm that MTC01 is not less effective than FMT. Whether just 15 strains of bacteria would be sufficient for rejuvenation in humans is entirely speculative – we’re not even sure that FMT is beneficial in healthy humans, and we don’t have a good grasp on which bacterial strains are important for ageing. However, the ability to grow combinations of human bacteria will make testing these ideas easier, and we may eventually be able to grow more complex, diverse microbiota that are closer to that found in FMT.

Probiotics and prebiotics might help preserve a youthful gut microbiota to some extent, but there is ultimately no substitute for FMT. This is because probiotics (live bacteria) that you can buy or get from food are not native to the human gut, so they don’t survive there for long. Prebiotics (fibre that is consumed by gut bacteria) can only nourish bacteria that are already present in the gut, but cannot restore what has been lost during ageing.