Longevity Briefs: How Bacteria Could Make The Gut ‘Leaky’ In Old Age

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:

Exosomes are a topic of growing interest when it comes to the ageing process. These microscopic membrane packages are loaded with genetic material and signalling molecules and are released by cells into the blood. They are then carried throughout the body and absorbed by other cells, acting as a form of ‘long distance communication’. Some research suggests that exosomes may play an important role in the ageing process, as the composition of their cargo changes with age. Mouse studies show that blood from younger mice has rejuvenating effects in older mice, and exosomes seem to be at least partially responsible for this.

Exosomes are not just released by human cells – the bacteria in our gut also release exosomes, and some of these exosomes may be absorbed into the blood. We know that the composition of the gut microbiota (the entire population of microorganisms that live in the gut) changes with age, and that this has a negative influence on human health. In this study, researchers investigate how the contents of the exosomes present in the intestines changed with age in mice, and whether feeding mice exosomes from animals of different ages would have an effect on health.

The discovery:

Researchers harvested exosomes from the guts of ‘young’ 12 month-old and ‘old’ 24 month-old mice, which roughly correspond to humans in their 30s or 60s in terms of ageing, respectively. After collecting faecal samples and isolating the exosomes, researchers then delivered those exosomes to groups of 5-6 young mice via their food. They found that exosomes from old mice increased the permeability of the recipients’ intestinal walls, allowing more fluorescent dye to pass into their blood compared to those exposed to exosomes from young mice. Researchers also found that young mice that received exosomes from old mice had significantly higher blood sugar levels and did not respond as well to insulin, the blood sugar-lowering hormone.

Researchers also analysed and compared the contents of the intestinal exosomes from young and old mice using a ‘multi-omics’ approach. This essentially means that they analysed multiple different types of molecules simultaneously to gain a complete understanding of what the exosomes contained. They identified differences in levels of proteins and miRNA (short strands of RNA that can suppress genes) associated with immune regulation, metabolism, protein production and responses to cellular stress.

The implications:

This study suggests that exosomes produced by gut microorganisms may have a role to play in age-related changes in intestinal function and metabolism. As the composition of the gut microbiota shifts, there is also a shift in the cargo of the exosomes being produced, contributing to the age-related decline in insulin sensitivity and an increase in intestinal permeability, or so-called ‘leaky gut’.

The term ‘leaky gut’ has something of a bad reputation, as it has often been used to push pseudo-scientific treatments. Contrary to some claims, there is no such thing as a ‘leaky gut syndrome’ diagnosis, and ascribing gastrointestinal symptoms to ‘leaky gut syndrome’ can delay identification of diagnosible health conditions. However, there is evidence that gut permeability increases with age, potentially allowing some molecules to pass into the bloodstream and trigger chronic inflammation, which could increase the risk of age-related diseases. There is also evidence that lifestyle factors like diet and exercise can help preserve intestinal barrier function. The findings of this study raise the possibility that extracellular vesicles might also be harnessed to improve barrier function, provided that the specific extracellular vesicle cargo that is responsible can be identified.