Longevity Briefs: How Good Gut Microbes Could Improve Eyesight And Protect Against Brain Ageing

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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 composition of the gut microbiome – the diverse populations of microorganisms living in the gut – can have a profound effect on many aspects of health. The health of the immune system, the central nervous system and even the eyes is associated with the health of the gut microbiome. We also know that the diversity of the gut microbiome decreases during ageing, and populations of harmful bacteria can grow while beneficial bacteria dwindle.

When it comes to ageing and the microbiome, disentangling cause and effect can be tricky: do changes to the gut microbiome promote ageing, or does ageing have a negative effect on the gut microbiome? Animal studies lend credence to the former, as transferring gut bacteria from younger to older organisms has been found to extend the lifespans of the recipients. How does this work, and what specific effects does receiving a ‘young’ microbiome have on the organs of an older animal?

What did the researchers do: In this study, researchers took 87 mice that were either 3, 18 or 24 months old. As a proportion of lifespan lived, this is roughly equivalent to 11, 63 or 84 year-old humans respectively. Some mice received faecal microbiome transplants from donor mice that were older or younger than them, while other mice received transplants from donor mice that were the same age. Some mice instead received a control treatment. This made for groups of around 7 mice each.

Researchers then studied the effects of these treatments on the mice’s behaviour and on the health of the gut, brain and retina.

Key takeaway(s) from this research: Microbiome transplants had a powerful effect on inflammation in the brain and eyes, which is thought to be one of the hallmarks of ageing. When young mice received microbes from older mice, immune cells in their brains called microglia became more inflammatory (this is thought to play a key role in brain ageing and dementia) while the reverse occurred in old mice transplanted with ‘young’ microbiomes. However, this didn’t have a significant effect on the mice’s performance in any of the cognitive tests the researchers used. This could be because the study didn’t last long enough for the effects of reduced inflammation on the brain to manifest. It’s also possible that damage to the brain caused by inflammation is not reversible, but that treatment would still have prevented further cognitive decline if the study had lasted longer.

Similar effects of microbiome transplants were found in the retina of the eye: ‘young’ microbiomes reduced inflammation in the retinas of older mice, and also restored levels of a key retinal pigment called RPE65, which is essential for normal vision.

In the gut itself, receiving an ‘old’ microbiome weakened the barrier between the intestine and the blood, allowing more bacterial products to enter the circulation and increasing the production of harmful inflammatory molecules. As before, receiving a ‘young’ microbiome had the reverse effect.

How changes to the gut microbiome work their way up to affect the central nervous system. **Left:** In mice with a young microbiome (either because they were young to begin with, or received bacteria from an younger mouse), bacterial products are contained within the gut. **Right:** In mice with an old microbiome, the gut becomes more permeable and bacterial products leak out. This leads to increased inflammatory molecules in the blood, which activates microglia in the brain and damages the retina in the eye.
*Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain*

Finally, they identified some of the changes in microbiome composition that were associated with the above effects. Animals receiving ‘old’ microbiomes had more Prevotella, Lacnospiraceae, and Facecalibaculum species, while those receiving ‘young’ donor bacteria had more Bifidobacteria, Eubacteria, and Akkermansia species.

Overall, the study paints a picture of how changes in gut bacteria populations can impact the gut wall, leading to increased inflammation throughout the body and promoting changes associated with ageing in the central nervous system. Fortunately, the potential to reverse these changes by transplanting healthier microbiomes exists, but future studies will need to look at whether the effects of this are long-lasting and whether they translate to improved cognitive/visual function.