Reference:
Wilmanski T, et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab. 2021 Feb;3(2):274-286. doi: 10.1038/s42255-021-00348-0. Epub 2021 Feb 18.
Summary
A recent article points out that the gut microbiome has important effects on human health, and its importance in human aging represents a promising field of research. Starting in mid-adulthood, it has been shown that the intestinal microbiome takes on an increasingly individual profile, continuing to differentiate over the years. The cohort study, which analyzed three independent cohorts comprising over 9,000 individuals, found that the uniqueness of the microbiome composition is strongly associated with amino acid derivatives produced by intestinal bacteria and circulating in the bloodstream. In old age, over 80 years, healthy individuals show a continuous microbial drift towards a unique compositional state, while this drift is absent in less healthy individuals. The characteristic microbiome pattern of healthy aging is characterized by a depletion of the main types of microbiomes found in most humans, especially Bacteroides. Maintaining a high predominance of Bacteroides in old age, or having a low level of gut microbiome uniqueness, predicts a decrease in survival in a 4-year follow-up. This analysis identifies the increasing uniqueness of the gut microbiome composition as a component of healthy aging, which is characterized by distinct metabolic microbial outputs into the blood.
Background
The human gastrointestinal tract hosts a complex and dynamic population of microorganisms, the gut microbiome, that exerts a marked influence on the host during homeostasis and disease. Multiple factors contribute to the formation of the human microbiome during childhood, and diet is considered one of the main factors. Gut bacteria play a crucial role in maintaining immune and metabolic homeostasis and in protecting against pathogens. Altered intestinal bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The collection of bacteria that colonize the gastrointestinal tract has evolved along with the host over thousands of years to form an intricate and mutually beneficial relationship. Calculating the number of microorganisms that populate the gastrointestinal tract is very difficult. Initially the number appeared to be over 1014, which is about 10 times higher than the number of human cells. However, a more recent estimate suggests that the ratio of human cells to bacteria may be closer to 1:1. In any case, given the large number of bacterial cells present, the microbiome is considered similar to an accessory organ.
Several studies conducted in centenarian populations provide potential insights into microbial variations associated with aging. For example, it has been shown that the intestinal microbiomes of centenarians and supercentenarians (over 104 years old) show a depletion of the most common bacterial species present at a young age (Bacteroides, Roseburia, and Faecalibacterium), offset by an increase in the prevalence of rarer species. Nowadays, similar results have been reported in other centennial populations around the world, such as in Sardinian, Chinese and Korean centenarians, compared to younger, healthy populations. This suggests that the gut microbiome continues to develop within its host, even in the last decades of human life.
The results achieved
The research reports the results obtained from the study of over 9,000 individuals and highlights that, as people age, the composition of this complex community of microbes tends to change and the greater the change, the better.
In healthy people, the types of microbes that dominate the gut in early adulthood make up an increasingly smaller proportion of the microbiome over the following decades, while the percentage of other less prevalent species increases. However, in people who are less healthy, the opposite happens. In fact, the composition of their microbiomes remains relatively static and subjects tend to die earlier.
This study finds that people whose gut microbiomes did not undergo major changes as they aged were in poor health. They had higher cholesterol and triglycerides as well as lower levels of vitamin D. They were less active and could not walk very fast, took more medications, and were almost twice as likely to die during the study period. Conversely, people who experienced the most changes in their microbial makeup tended to have better health and a longer lifespan. They had higher levels of vitamin D and lower levels of low-density lipoprotein, cholesterol, and triglycerides. They needed fewer medications and had better physical health, with faster walking speeds and greater mobility.
Researchers found that some gut bacteria that is harmless or perhaps even beneficial in early adulthood could become harmful in old age. For example, in healthy people who saw the most dramatic changes in their microbiome composition, the study found that there was a sharp decline in the prevalence of bacteria called Bacteroides. Bacteroides are more common in developed countries where people eat a lot of processed foods (rich in saturated fat, simple sugars, and salt) and less prevalent in developing countries, where people tend to eat a diet rich in whole grains and fiber. When fiber is not available, Bacteroides consume the mucus that forms the protective layer of the intestine. Since the intestine tends to produce less mucus as we age, at some point Bacteroides become harmful.
Outlook and practical implications
One way to stop Bacteroides from destroying the gut lining is to give them something else to feed on, such as fiber from whole foods including beans, nuts, seeds, fruits, vegetables, and whole grains.
It is very important to remain physically active, because exercise can have a beneficial effect on the intestinal microbiome, and it is essential to eat fewer highly processed foods.
Researchers have discovered the importance of several metabolites produced by intestinal microbes in the blood. Molecules belonging to the class of indoles, for example, have demonstrated an ability to reduce inflammation and maintain the integrity of the barrier that covers and protects the intestine. Indoles are widespread in the plant world, but particularly in white vegetables (cauliflower, celery, fennel, potatoes, beans, almonds, and champignon mushrooms). Another metabolite identified in the study is phenylacetylglutamine. It is not clear exactly what this compound does, but research has shown that centenarians in northern Italy tend to have very high levels of it, leading some experts to believe it promotes longevity.
Researchers are trying to identify other ways to reduce the abundance of Bacteroides. At the moment, the best weapon we have are our dietary habits. Always remember that when we feed ourselves, we are also feeding our gut microbes.
Edited by Claudio Molinari
