Microbiome and Aging
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I recently came across an article in the NYTimes titled, A Changing Gut Microbiome May Predict How Well You Age. The article talks about the gut microbiome and its role in healthy aging. The author quotes a new study published in the February issue of the journal Nature Metabolism which found it may be possible to predict the likelihood of living a longer, healthier life by analyzing your gut microbiome.
“The gut microbiome goes through different developmental phases.”
It has been known for some time, that the gut microbiome goes through different developmental phases, starting with fairly dramatic changes during the first 1000 days of life, followed by a relatively stable period throughout adolescence and adulthood, and ultimately by a relative decline in certain health promoting microbes (such as Faecalibacterium, Roseburia, Eubacterium), as well as a decrease in microbial diversity in the elderly. These changes in the elderly have been associated with clinical measures of frailty and cognitive decline.
“The gut microbiome becomes increasingly unique to the individual with age.”
The authors studied gut microbiome parameters in 3 independent cohorts, comprising over 9,000 individuals ranging in age from 18-101 years. They demonstrated that the gut microbiome in healthy individuals changes as we get older, and this change is a sign of healthy aging. The researchers found that beginning in mid-to-late adulthood, the gut microbiome becomes increasingly unique to the individual with age, with a relative decrease in the abundance of certain bacterial taxa (mainly of the genus Bacterioides), and this uniqueness was positively associated with known microbial metabolic markers – primarily tryptophan and phenylalanine/tyrosine metabolites – previously implicated in immune regulation, inflammation, ageing and longevity.
“Retention of high relative Bacteroides abundance and a low gut microbiome uniqueness measure were both associated with significantly decreased survival.”
In the later decades of human lifespan, healthy individuals continued to show an increasingly unique gut microbial compositional state (associated with a decline in Bacterioides but not Prevotella taxa with age, whereas this pattern was absent in those in worse health. In individuals approaching extreme age (85+ years), retention of high relative Bacteroides abundance and a low gut microbiome uniqueness measure were both associated with significantly decreased survival in the course of a 4-year follow-up. Interestingly, the age-related gut microbial changes were not found to be related to differences in diet or medication use, both of which typically change with increasing age, and both of which have previously been associated with gut microbial changes.
“At age 80+ years, healthy subjects showed a continued trajectory towards increased gut microbial uniqueness.”
In older age (80+ years old), healthy subjects showed a continued trajectory towards increased gut microbial uniqueness whereas the opposite is the case in less healthy subjects. The term “gut microbial uniqueness” reflects how dissimilar an individual’s gut microbiota are from their nearest neighbour, given all other gut microbiome samples in the cohort: the higher the value, the more distinct the gut microbiome from everyone else’s in the studied population.
Even in the adult population, there is considerable uniqueness of microbial composition, starting with the interindividual variation of relative abundances of the dominant phyla Firmicutes and Bacterioidites. Part of the variation of adult gut microbial composition is related to dietary habits. For example, within the phylum Bacteriodites, there are two main genus: Bacteroides, which is a dominant taxa in those who eat plenty of protein and animal fats (like in the Standard American Diet), while for those who consume more complex carbohydrates (like in a largely plant based diet), the genus Prevotella dominate. People on average share about 30 percent of their gut bacterial species, a similarity that decreases further at the strain level, where only about 10% of microbes are similar between individuals. But why would the gut microbial uniqueness increase even further with advancing age, and why would such a change be beneficial for healthy aging?
“It is likely that the observed benefits on healthy aging in this study were a reflection of lifestyle factors.”
The gut microbial ecosystem is highly adapative to changes in diet, medications, physical activity, and to signals from the brain, in the form of poor sleep, mood, poor social interactions, or chronic stress. For many people, changes in these factors come along with increasing age, sometimes in dramatic form. While brain and mind related factors were not addressed in this study, dietary habits were recorded but surprisingly were not correlated with gut microbial changes. The authors admit that assessment of dietary habits by questionnaire is generally unreliable, and future studies will have to further explore the likely influence of diet. It is likely that the observed benefits on healthy aging in this study were a reflection of the above lifestyle factors rather than a primary change in gut microbial composition and function. However, it is equally plausible that the relative increase in the Prevotella/Bacterioides ratio, a finding reported in studies showing the beneficial effect of a largely plant based diet on frailty and cognitive decline, and a reduction of markers of systemic immune activation does play such a causal role.
“Healthy aging may ultimately be related to the observed changes in neuroactive metabolites.”
The reported increase in interindividual differences in relative abundances of gut microbial taxa and the association of these changes with healthy aging may ultimately be related to the observed changes in neuroactive metabolites previously associated with compromised brain health, such as p-cresol and 3-indoxylsulfate and with the prevention of leakiness of the gut and subsequent immune activation. The findings fit well into the growing awareness that low grade immune activation in the gut is the result of a leaky gut which develops in response to an unhealthy gut microbiome. This gut based immune activation can spread throughout the body, a mechanism which may play an almost universal role in our current non-infectious chronic disease epidemic affecting every organ of the body. In other words, systemic immune activation and related chronic disease plays a major role in determining healthy aging and longevity.
Until we know the details of all the interactions of this complex brain gut microbiome system and their role in preventing frailty and premature aging, the findings of the current study support the benefits of a largely plant based diet which promotes a healthy gut microbiome with a high ratio of Prevotella/Bacteroides taxa, and which is the best therapy to prevent the widespread impact of systemic immune activation on our health.
E. Dylan Mayer is a graduate from the University of Colorado at Boulder, with a major in Neuroscience and minor in Business. He is currently completing his master’s degree in Human Nutrition from Columbia University. Dylan is fascinated by the close interactions between nutrition, exercise and human health, especially with regard to the brain-gut-microbiome system – and regularly posts his content on his Instagram (@mayerwellness).