Reviewing What is Known of the Aging of the Gut Microbiome – Fight Aging!

Evidence obtained from animal and human studies in recent years suggests that the composition of the gut microbiome influences long-term health to a similar degree as choices relating to exercise and dietary choices. Certainly, the balance of populations making up the gut microbiome changes with age. Pro-inflammatory microbes grow in number at the expense of microbial populations responsible for the generation of beneficial metabolites, such as butyrate, which is known to upregulate neurogenesis. This process of gut microbiome aging begins quite early in adult life, perhaps as early as the 30s. These shifts may or may not be connected to shifts in the immune system and its ability to clear problematic microbes.

Fortunately several approaches to therapy have been demonstrated to produce a lasting rejuvenation of the gut microbiome, at least in animal models. Arguably the best of these is fecal microbiota transplantation using stool samples from a young donor. In animal studies, this approach as been shown to produce a lasting change in the balance of populations of the gut microbiome, improve health, and extend life span. This approach is used as a therapy in the treatment of C. difficile infection, but is not otherwise well developed. For those intent on trying this for themselves, it is possible to purchase screened stool samples from groups like Human Microbes. That screening for potentially problematic microbes in the donor sample is increasingly important as recipient age increases, as older people can be vulnerable to microbes that a younger person can tolerate.

The human gut microbiome and aging

The gastrointestinal microbiome is the collection of bacterial cells that reside within the human gastrointestinal tract representing more cells that are contained within the human body, and a metagenome (combined genome of these commensal organisms) that is far larger than the human genome. This community of organisms has been observed to change over the lifespan. Machine-learning-based analysis of published gut microbiome datasets could predict a subject’s chronologic age within 5.9 years, although this study was conducted largely independent of any health information. A cross-sectional study across the lifespan (age 1 to over 100) in a Japanese population showed a characteristic microbiome within infants and young children prior to weaning, then a transition to a more diverse microbiome associated with introduction of solid foods. This diverse and dynamic microbiome develops until early adulthood and then becomes relatively stable when it begins to show a decline in diversity after peaking late in life (around 65) and becoming more pronounced in individuals older than 80 years.

Researchers have observed microbiome signatures that became more unique to the individual at extremes of age which may reflect the microbiome becoming tailored to the individual’s diet and living environment that perhaps varies less at extremes of age. Intriguingly, very long-lived individuals (over 100 years old) have shown a distinct gut microbiome profile with greater diversity a high abundance of health-associated taxa such as Christensenellaceae and Akkermansia. Although the gut microbiome changes across the lifespan, there are features that have been associated with diseases that develop at different phases of life and contribute to the development of age-related disease later in life. Of particular interest are the microbiomes of “super-agers” who reach extremes of age in relatively good health and have the potential to offer insights into how the microbiome can affect longevity and resistance to age-related diseases.

Although age itself likely contributes to changes in the gastrointestinal microbiome, it is also greatly impacted by the environment in which an individual lives and ages. An exploration of data from metagenomic sequencing of microbiome samples across Europe, Africa, North and South America showed that there were distinct features of each geographic area throughout the lifespan. Much of the literature notes changes in taxa with age that tends to be conserved across different areas of the world. There are, however, notable differences depending on the region in which the study was undertaken. Studies of cohorts in Italy and Ireland have shown decreased abundances of Roseburia with aging, while studies cohorts in Korea and China have reported increases in this genus. Bacteroidetes are generally described as increasing with age, but the converse was observed among healthy older Indonesians. A study of healthy centenarians from India and comparing them with studies previously mentioned from Italy, China, and Japan found unique features in the Indian population such as lower Bacteroidetes, higher Enterobacteriaceae among the Indian cohort. Akkermansia, usually associated with healthy aging, was associated with frailty in a cohort of Chinese older adults.

These discrepancies highlight the extremely complex relationship between the gut microbiome and aging, which is affected not only by the myriad interactions between the host-specific organisms in the microbiome, but also the diet and environment in which the individual ages.