Can certain fungi or bacteria in your gut influence your cellular ageing?
Certain gut bacteria produce substances that accelerate cellular ageing, while a diverse microbiome rich in fibre-fermenting bacteria is actually protective. You can already take this into account through a high-fibre diet, but direct interventions in humans have barely been studied.
Two specific substances produced by certain gut bacteria appear to actively accelerate cellular ageing. Phenylacetylglutamine (PAGln) damages the mitochondria and DNA of cells through a signalling chain involving adrenergic receptors and the energy-sensor protein AMPK. A bacterium from the Clostridium family produces a related substance, phenylacetic acid (PAA), which ages blood vessel cells and inhibits the formation of new blood vessels. These effects were measurable in mouse experiments, and both PAA and PAGln were elevated in older people. Whether blocking these pathways in humans actually changes anything is not yet known.
On the other hand, a healthy gut microbiome actively protects against cellular ageing. Gut bacteria that produce short-chain fatty acids, such as butyrate and acetate (acetic acid), suppress inflammatory signals secreted by senescent cells. As we age, acetate production in the gut declines, reducing this protection. Sodium acetate as a supplement restored this effect in mice, but there are no studies in humans. A systematic review of 27 human studies consistently found that the oldest and healthiest elderly individuals had more of these short-chain fatty acid-producing bacteria, supporting the protective side of the story.
Shorter telomeres, the protective caps at the ends of chromosomes, are associated in association studies with higher levels of disease-causing bacteria such as streptococci and certain E. coli strains in the stool. The relationship between gut microbiota and telomere length also works in both directions: the gut microbiome influences telomere maintenance, but a well-functioning telomere structure also protects the gut barrier. The precise mechanisms involved are still largely unresolved.
A disrupted gut microbiome (dysbiosis) amplifies chronic low-grade inflammation in the body, and this promotes cellular senescence that contributes to bone loss, muscle wasting and joint complaints. Conversely, senescent cells also shape the composition of the gut microbiome. The relationship is therefore reciprocal, which makes it difficult to separate cause from effect. Most studies on this topic are observational or based on review literature.
Regarding fungi in the gut: the studies provided deal exclusively with bacteria and their metabolites. Whether fungi in the gut microbiome also play a direct role in cellular ageing cannot be determined on the basis of this evidence.
Evidence from two non-indexed studies (cell and mouse models), a systematic review of 27 human studies, multiple reviews and an association study in chronically ill patients. No randomised trials in humans are available. Causal relationships in humans have not been established for most mechanisms.
Does my gut microbiome change as I get older, and does it matter?
Your gut microbiome certainly changes as you get older, but whether that is harmful depends strongly on which direction that change goes. What you eat has a major influence on this, so that is a concrete area to pay attention to.
Can your gut microbiome influence how long you live?
There are clear indications that the composition of your gut microbiome is associated with how long and how healthily you age, but whether modifying your microbiome extends your life has not yet been demonstrated in humans.
Can a disrupted gut microbiome weaken your immune system?
A disrupted gut microbiome demonstrably dysregulates your immune system and increases the risk of chronic inflammation. Eating fermented foods is the best-supported way to do something about it.
Can your gut microbiome influence inflammation in your body?
Your gut microbiome can influence inflammatory processes throughout your body via the gut wall. Eating more fibre and exercising regularly are the most well-supported ways to influence this favourably.
Can an unhealthy gut contribute to skin problems such as acne or eczema?
A disrupted gut microbiome is associated with acne and eczema, although that association has not yet been proven to be cause and effect. Eating more fibre and plant-based foods is a sensible first step; for targeted probiotics the evidence is still too mixed for a clear recommendation.
Can your gut microbiome affect your cholesterol?
Your gut microbiome influences your cholesterol through bile acid conversion and the fermentation of fibres. Eating more fibre is the most concrete and safe step to take; supplements such as berberine are not yet sufficiently substantiated for daily use.