The gut microbiome is a significant regulator of the immune system and brain health. As we age, we typically experience a decrease in overall health, especially in our brain function and the immune system. Research has shown that our gut microbiome has been linked with both these factors. As a result, researchers have questioned whether we can reduce these changes by altering our microbiome?
The Impact of the Microbiome on Ageing
The microbiome has an important effect on human health. Our immune system has evolved to rely upon many of the beneficial bacteria found in our gut. The dramatic changes to the microbiome we see during the ageing process are often linked to the decline in immune function that we experience during ageing. This ultimately leads to poorer health among elderly populations. However, we are yet to fully understand how the microbiome affects brain health and neuroimmunity during ageing.
Transplanting Young Microbiota into Old Mice
A new study from the University College Cork, published in Nature Aging, investigated how faecal microbiota transplants (FMT) from young and old mice can alter the microbiome of aged mice. They also explored how these changes affect brain immunity, the hippocampal metabolome and the transcriptomes of mice.
The researchers transplanted faecal microbiota from both naïve young mice (3-4 months) and naïve old mice (19-20 months) into aged mice (19-20 months). This created two groups: young faecal microbiota transplantation (yFMT) and old faecal microbiota transplantation (oFMT). These groups were then used to compare the effects of the microbiome on the ageing process.
The team found age-associated differences in the microbiome, behaviour, neurogenesis and transcriptomics of the yFMT mice, but no changes in the oFMT mice.
Investigating Changes in the Immune System Following FMT
It has been suggested that changes in immunity that are linked to alterations in the microbiota as we age are also associated with changes in the brain that happen during ageing. As a result, researchers investigated if ageing-invoked immune alterations could be returned following the yFMT. Notably, CD8+ T-cells levels were restored, along with levels of F4/80+ macrophages. However, interferon–y and IL-5 levels remained the same.
Along with the recovery of some immune cell levels, five genes (Trem12, Dap12, C1qb, Gpr84, Fcgr2) that regulate the microglia were found restored to original levels in the yFMT mice. Notably, the expression of Gpr84, which is elevated in mouse models with multiple sclerosis and Alzheimer’s disease, was found to be reduced to its original levels.
How yFMT Shapes the Hippocampal Metabolome
The hippocampal metabolome changes significantly during the ageing process. In yFMT mice, researchers observed that 35 metabolites were restored towards the levels found in young mice. For example, retinol (Vitamin A) levels were observed to be significantly reduced in the ageing process but were restored in yFMT mice. This suggests that the decrease in retinol can be restored through the addition of vitamin A supplements. Furthermore, GABA and N- glycolylneuraminate levels were recovered in yFMT mice, both of which play a significant role in cognition and brain plasticity.
In this study, researchers demonstrated that transplantation of a young faecal microbiome into aged mice restored levels of gene expression, proteins and metabolites. This highlights the importance of retaining a healthy microbiome to combat the negative effects of getting older. These findings may enable researchers to discover the mechanisms through which the gut microbiome has specific effects in restoring levels of gene expression, metabolites and immune cells in an ageing brain.