Although researchers now know that the gut microbiome changes as humans age and that age-related diseases may also affect the gut microbiome, how targeting the gut microbiome may lead to healthier aging or reduce the risk of age-related diseases it is still unknown. Besides genetics, diet and other lifestyle factors such as medication use and social interactions, the gut microbiome may therefore be a key factor in healthy aging.
A comprehensive review by O’Toole and colleagues, in Nature Reviews Gastroenterology & Hepatology, discusses new research about what we know so far on the involvement of the gut microbiota in aging and gut microbiota-related interventions studied for improving some age-related changes.
Various aspects of aging affect the gut microbiome, including decreased appetite, stomach acid, digestive enzymes, mucosal immunity and intestinal barrier function, increased social isolation and use of medications such as antibiotics. On the other hand, the gut microbiome can also accelerate or slow down some body changes that occur with aging.
In general, as humans age, the amount of protective bacteria decreases while potentially harmful bacteria increase in abundance in the gut, along with inflammation and fragility.
Studies from various countries such as France, Japan, Italy, Russia, China and India have also revealed that centenarians, or “extreme aging”, is associated with a boost in several health-associated bacteria such as Akkermansia spp. However, it is important to note that extreme aging is not necessarily associated with healthy aging, which, in turn, is linked to more physical activity, a balanced diet and low cognitive decline. In line with that, unhealthy aging can occur at any age.
The authors of the review divided the current studies into two types: those that focus on changes that occur in the gut microbiome due to natural aging, and those that analyze how age-related diseases affect the gut microbiome. From the studies, the researchers identified three main patterns of bacteria (taxa) that alter during aging or age-related diseases. They identified three specific groups of bacteria that were either increased or decreased and either associated with healthy or unhealthy aging.
Healthy aging Group 1 consisted of bacteria, such as Bifidobacterium, that decreased with age and were associated with healthy aging. Group 2 was associated with unhealthy aging and included bacteria that potentially cause disease such as Streptococcus, Actinomyces and Eggerthella, along with an increase in genes involved in breaking down drugs and chemicals. Healthy aging Group 3 included bacteria such as Akkermansia, which increased with age but were seen to be reduced in cases of unhealthy aging. In other words, Groups 1 and 3 were associated with healthy aging, whereas Group 2 was associated with unhealthy aging, which can include increased frailty, inflammation, cardiovascular and metabolic disorders and cognitive decline.
Those changes in gut microbiota composition could be linked to important changes in the physiology of the elderly population. Importantly, in addition to bacteria, the authors also linked each group with microbial metabolites and associated disorders. For example, unhealthy aging Group 2 was associated with DNA-damaging compounds that could lead to colorectal cancer, as well as the metabolite trimethylamine, which has been associated with cardiovascular disease and inflammation. Conversely, Groups 1 and 3 were associated with the beneficial short chain fatty acid butyrate, which may be protective against certain diseases such as cognitive disorders and obesity.
The review also discusses the importance of creating more comprehensive long-term studies in the elderly population that analyze how certain interventions that target the gut microbiome, such as probiotics and diet, may affect aging. Despite the lack of well-designed studies in that population, the first multinational, comprehensive, long-term study performed in older people showed that following a strictly traditional Mediterranean diet for a year led to a healthy, stable shift in the gut microbiome and an increase in healthy bacteria that resulted in higher health metrics such as reduced frailty and inflammation and increased cognition compared to individuals who maintained their normal diet.
Other studies have also shown that consuming probiotics, prebiotics, and polyphenols found in many plant foods such as blueberries can increase beneficial butyrate-producing bacteria such as Faecalibacterium and Coprococcus, which have also been found to maintain a healthy intestinal barrier.
Conclusion and takeaway
Despite intervention studies that have analyzed the effects diet, prebiotics and probiotics may have on the gut microbiome and overall health, information about their long-term impacts remains limited. The authors conclude that many questions are yet to be investigated in the elderly population. They include: can missing bacteria be replaced, or what specific dietary requirements are needed to restore the gut microbiome to a healthy state?
Predictive models using machine learning and more sensitive gut microbiome analyses are likely needed to determine which personalized dietary interventions are necessary to restore and maintain a gut microbiome that promotes healthy aging. Moreover, policy makers need to focus on better messaging around how to maintain a healthy diet and how to make healthy food more affordable and available to everyone regardless of socioeconomic status.
Reference: Ghosh, T.S., Shanahan, F. & O’Toole, P.W. The gut microbiome as a modulator of healthy ageing. Nat Rev Gastroenterol Hepatol (2022). https://doi.org/10.1038/s41575-022-00605-x