Longevity Briefs: Targeting Gut Bacteria To Slow Cognitive Ageing

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:

Some degree of cognitive decline is to be expected with advancing age, but cognitive decline can be significantly slowed or prevented through healthy lifestyle practices. While traditional approaches focus on brain health, a growing body of research points to an unexpected player: the gut. The microorganisms that live in the gut, collectively known as the gut microbiota, appear to have a significant impact on brain function owing to the release of certain key beneficial molecules by bacteria. These molecules can affect both brain health and the function of the immune system, with immune cells being heavily present in the intestines while also having a significant impact on brain health. Furthermore, the vagus nerve connects the gut and the brain directly. This allows the brain to control gut function, but it appears that bacteria can also have a direct effect on the brain by modulating the activity of the vagus nerve.

Despite our ever-growing understanding of how gut health can impact brain function, the idea of using interventions targeting the gut in order to enhance brain health is relatively unexplored. We know that loss of gut microbiota diversity in old age correlates with cognitive decline, but the only way to prove that changes in the microbiota cause cognitive decline is to try boosting gut health in a group of people and see if cognitive function is improved. In this study, researchers conduct a systematic review of pre-existing studies that followed cognitive function in people receiving microbiota-targeting interventions.

The discovery:

A systematic review involves gathering and analysing existing high quality scientific studies in order to draw a broader conclusion, in this case to determine whether interventions targeting the gut microbiota could mitigate cognitive decline in people who either had dementia or were at risk. They identifying 15 clinical trials that met their criteria, involving a total of 4275 participants who were mostly over the age of 60.

The interventions studied ranged from more direct interventions such as probiotics (consumption of beneficial live bacteria) and faecal microbiota transplantation (FMT, stool transplants) to less direct methods such as dietary interventions and supplements designed to support a healthy gut microbiota. The studies tracked cognitive performance, biomarkers related to inflammation and gut microbiota composition, with follow-up periods ranging from 8 weeks to over 6 years.

• Most indirect interventions were associated with a statistically significant improvement in microbiota composition and cognitive score compared to controls. These included Mediterranean, ketogenic diets and DHA omega-3 supplementation, while another omega-3 supplementation study resulted in a non-siginicant trend, and an omega-3 and polyunsaturated margarine had no significant impact on dementia progression. Improvements were generally seen in memory, executive function and global cognition.
• All but one study of probiotics, sometimes combined with fibre such as inulin, found a statistically significant improvement in cognitive function and beneficial changes in gut microbial diversity.
• Only one study of FMT was included, but reported significantly improved cognitive scores in participants with Alzheimer’s disease. These improvements were seen in memory, attention, language, and problem-solving. Changes in gut microbiota composition were greater and occurred rapidly compared to dietary interventions and probiotics.

The implications:

Though still limited in nature, existing evidence suggests that modulating the gut microbiota can improve specific cognitive aspects in people with or at risk of cognitive decline. The effects of these interventions were generally weaker in those who already had cognitive decline or dementia.

Note that while this was a review of multiple studies, it was not a meta-analysis, where data from multiple studies is combined and analysed using statistical techniques in order to determine whether findings are significant across those studies. Rather, this review shows that quality studies of microbiota-targeting interventions tend to report favourable effects on cognition. It also doesn’t prove that all studied interventions had their effects on cognition through altering the gut microbiota.

Though data remains limited, faecal microbiota transplantation appears to be particularly promising. Microbiota transplantation from a healthy donor is currently the most effective way of restoring microbiota health in a lasting way. While most probiotics are not native to the human gut and don’t survive there for long, a single faecal transplant is sufficient to alter microbiota composition long-term. Unfortunately, the long-term effects of FMT on health are still mostly unknown.