This research is a representative example of ongoing efforts to better understand changes in the gut microbiome with age, identifying how and why specific microbial species are either protective or harmful to health. The gut microbiome is responsible for generating a range of helpful metabolites, but can also interact with tissues and the immune system to provoke chronic inflammation. It has been noted that some known beneficial populations decline while some known harmful populations grow in number with advancing age - though there is a great deal of work remaining to produce a full map of the effects of microbial species on health and aging. Fortunately, some short-cut approaches have been shown to favorably adjust an aged gut microbiome, such as fecal microbiota transplantation and flagellin immunization. Widespread clinical use still lies in the future, even through such approaches are quite accessible to self-experimenters.
Bifidobacterium species are pioneer colonizers of the gut and have been associated with various health-promoting effects, although the precise modes of action remain largely unknown. The abundances of various Bifidobacterium species in the gut vary widely among individuals according to dietary habits, age, and physiological status. One exception is Bifidobacterium longum (B. longum subsp. longum), which belongs to the human core microbiome. This species accounts for a higher proportion of Bifidobacterium species in the gut regardless of host age, is distributed broadly across the human lifespan, and is among a small subset of gut commensals that can colonize the gut for years.
Using a conceptual framework based on evolution and the pathogen transmission theory, we showed that B. longum had formed at least three geographically related populations and established the active transmission of B. longum strains across different types of hosts and according to geography and proximity. Interestingly, we identified a strong and statistically significant association between host age and genetic variations in B. longum genomes.
Our data also provide a molecular basis for host-microbe coevolution, and this knowledge could feasibly be used to promote host health. The causal link between the gut microbiota and host aging has been investigated extensively, and microbiome-based therapies such as dietary interventions, probiotics, and fecal microbiota transplantation have been shown to efficiently alleviate host aging. Some bacteria have been associated with a long human lifespan by analyzing the gut microbiota of centenarians. No chronological threshold or age is associated with an abrupt change in the microbiota composition; rather, these changes proceed gradually over time.
We identified a strong negative association of the genus Bifidobacterium with host age, consistent with previous observations of reduced bifidobacterial counts in the elderly compared with the gut microbiota of two or three other age groups. We further investigated the bifidobacterial species-level composition and identified B. longum as the most dominant of the core bifidobacterial species in the studied cohort. We further determined that the relative abundance of B. longum was also significantly correlated with host age. Interestingly, efforts to associate the genotype of this aging-related species with host age revealed a robustly significant association with the bacterial arginine biosynthesis pathway.
Previous studies have demonstrated many molecular mechanisms by which microbiota may favorably affect host health and aging, based on principles designed to seek possible solutions to those changes experienced during the aging process, including (1) decreased immune system functioning (i.e., immunosenescence) and low-grade chronic inflammation (i.e., inflammaging); (2) inappropriate oxidative stress; (3) impaired gut barrier function; (4) decreased energy supply for colon epithelial cells; and (5) perturbed gut metabolism (e.g., lipid metabolism, glucose homeostasis, vitamin B and conjugated linoleic acid production). Here, we propose another potent mechanistic route that key players (B. longum) in the gut microbiota are capable of generating age-related genomic adaptations in the arginine metabolism pathway, enhancing the bacterial arginine-enriching ability, further modifying arginine flux and the overall metabolome in the gut microbiota, and ultimately achieving protection against host aging.