This topic was discussed at this year’s IPA World Congress + Probiota, with Dr. Sean Gibbons, associate professor at the Institute for Systems Biology, discussing the latest research that has investigated the drivers of healthy gut aging signatures and the potential metabolic consequences.
To conduct their research, Dr. Gibbons and his team looked at data from two cohorts. The first, referred to as the Arivale cohort, consisted of around 3,600 people between the ages of 18 and 90, while the second—MrOS— included 1,000 men between the ages of 80 and 100.
“We looked at a lot of different features in the microbiome to try to see what was most associated with aging across these various cohorts,” Dr. Gibbon said. “Of all the things that we could measure, this thing called ‘uniqueness’ ended up showing the strongest association with age in these populations.”
The data showed that people’s gut microbiomes began to ‘drift’ in their 40s or 50s, with these changes accelerating towards the later years of life. This has been replicated in other independent cohorts which show similar associations.
Overall, this ‘uniqueness’ was associated with a decline in gram-negative anaerobes like Bacteroides and Prevotella, and a rise in subdominant taxa, mostly from clostridia (gram-positive anaerobes).
Is a unique gut microbiome associated with health and longevity?
To assess whether this shift was associated with overall health, the researchers analyzed the participants’ health status using various metrics.
In the MrOS cohort, the participants who were healthy had a stronger significant association of uniqueness and age. This association was not seen in those who were less healthy.
In other words, healthy older people had more distinct gut microbiomes compared to less healthy older adults, who tended to maintain core microbes that were dominant in their younger years.
In addition, Dr. Gibbons’ team found that participants in the highest tertile of Bacteroides abundance or the lowest tertile of uniqueness were significantly more likely to die over a four-year follow-up period.
“So the signature, whether it is ‘healthy’ or not, is predictive of survival in the latest decades of life,” he said.
Gut uniqueness was also reflected in microbe-derived metabolites in the blood. These findings were “paradoxical”, Dr. Gibbons said, as it appears people with high uniqueness often had a build-up of uremic toxins in the blood.
“There’s some nutritional data on diets across the lifespan,” Dr. Gibbons explained. “This data suggests that if you eat a high protein diet as a younger person, this is bad for your metabolism and can promote diabetes. But in older people, having a higher protein diet is actually protective against frailty it seems.
“Uremic toxins build up in the blood when you’re eating more protein. So maybe having a higher protein diet as you age overrides the negative effect of these toxins. It’s hard to say—we don’t quite know the answer yet.”
Could gut microbiome composition influence drug responses?
Dr. Gibbons’ team also looked at how gut microbiome composition may influence responses to drugs designed to minimize disease risk in older patients.
Statins are one of the most dominant life-span promoting drugs on the market, yet data suggests that there is huge variation in response rates, with around half the population classified as ‘non-responders’.
Looking at their cohort data, Dr. Gibbons’ team found that heterogeneous responses to statins may be explained by variations in the gut microbiome, with gut microbiome diversity inversely associated with statin efficacy.
Overall, the data suggests that maintaining high Bacteroides dominance and lower levels of butyrate-producing clostridia and Akkermansia muciniphila is associated with poorer metabolic health in statin users. These results were replicated in an independent European cohort, suggesting translational potential.
Dr. Gibbons said probiotics, particularly those containing Akkermansia muciniphila and butyrate-producing species like Faecalibacterium prausnitzii, could therefore help mitigate the metabolic side-effects of statins and improve overall metabolic health as people age.
Clinical implications
As fecal microbiota transplantation (FMT) becomes an increasingly popular treatment option for gut-related disorders, Dr. Gibbons says this research has important implications.
“If you’re 80, you probably don’t want a 20-year-old microbiome—this might not be good for you," he explained. “You probably want a microbiome that’s adapted to the physiology of your 80-year-old body.”
This is because many physiological changes happen as we age—the gut produces less mucus, the mucin layer thins, and transit time slows down.
“There are all these global effects happening in the ecosystem, so it stands to reason that the ecological composition of the microbiome for an older person could be quite different compared to a younger person,” Dr. Gibbons said. “So maybe we shouldn’t turn back the clock. I would suggest that people do not give FMTs from 20-year-olds to 80-year-olds [...] It’s too early and there’s not enough evidence for that.”
