FMTs now implicated in reversal of brain ageing and cognitive decline
The APC Microbiome Ireland (APC) team writing in Nature Ageing found the transplant of a microbiota from young donors reversed ageing associated differences in peripheral and brain immunity,
The young donor-derived microbiota also decreased certain age-linked impairments in cognitive behaviour when transplanted into an older host.
"Previous research published by the APC and other groups internationally has shown that the gut microbiome plays a key role in ageing and the ageing process,” explains Prof John Cryan, Principal Investigator at APC Microbiome Ireland, based in in University College Cork (USS).
“This new research is a potential game changer , as we have established that the microbiome can be harnessed to reverse age-related brain deterioration.
“We also see evidence of improved learning ability and cognitive function. It is still early days and much more work is needed to see how these findings could be translated in humans."
Transplantation process
The research conducted FMTs from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months) as the control. To allow ageing-associated comparisons, naive young mice received the same FMT mixture.
Findings revealed a host of ageing-associated differences in microbiota, immunity, hippocampal neurogenesis, metabolomics, transcriptomics and behaviour.
According to the team, some, but not all of these observations were attenuated by microbiota transplantation from a young mouse into an aged host.
Further discussions of the potential mechanisms underpinning the changes intestinal microbiota has on the host centred on several gut–brain modules and predicted microbiome functions that were altered following FMT from young mice (yFMT) to both groups.
The team suggests certain aspects of gut-linked, circulating and hippocampal immunity were restored following yFMT into aged mice, which likely drove restorations in immune functions that underlie improvements in age-associated cognitive deficits.
In addition, the team uncovered restorative effects of yFMT on the ageing hippocampal metabolome and transcriptome, which coincided with the improvements in behaviour.
Influencing brain health
“We hypothesise that gut microbiota-derived metabolites may play a role in the alteration in hippocampal metabolomics through indirect or direct mechanisms, as several of the metabolites we uncovered are able to translocate across the blood–brain barrier,” the researchers conclude.
“While specific ageing-associated deficits in behaviour, immunity and neurogenesis were not restored by yFMT, this research provides fundamental evidence that the gut microbiota should be considered as a potential therapeutic target for treating aspects of ageing-associated decline in hippocampus-related function.”
APC Director Prof Paul Ross adds, "This research of Prof. Cryan and colleagues further demonstrates the importance of the gut microbiome in many aspects of health, and particularly across the brain/gut axis where brain functioning can be positively influenced.
“The study opens up possibilities in the future to modulate gut microbiota as a therapeutic target to influence brain health"
Source: Nature Ageing
Published online: DOI: 10.1038/s43587-021-00093-9
“Microbiota from young mice counteracts selective age-associated behavioral deficits.”
Authors: Marcus Boehme et al.
