The gut microbiome is made of thousands of microbial species in various proportions, some helpful, some harmful. The development of means to accurately measure the composition of the gut microbiome, by sequencing the 16S rRNA gene that exhibits characteristic species-level differences, has enabled the scientific community to connect changes in the gut microbiome to aging, health, and disease. This mapping of the gut microbiome as a contributing factor in aging and age-related diseases is still in the relatively early stages, but as the field progresses we should expect to see increased interest in the development of novel, improved means to alter the gut microbiome as form of therapy.
The composition of the gut microbiome is fairly resilient to short-term changes induced by diet, present probiotic and prebiotic supplements, mild antibiotic use, and the like. It will bounce back. Over decades of life, however, changes do occur in the balance of microbial populations, and they are not favorable. Inflammatory microbes grow in number at the expense of microbes that generate metabolites necessary for optimal tissue function. Some of this is a consequence of long-term shifts in diet in older individuals, some of it is the decline of the immune system in its role as gardener of the gut microbiome, some of it is other factors. The relative importance of each of these items has yet to be concretely determined.
Fortunately there are ways to permanently change the gut microbiome. Flagellin immunization will direct the immune system to more aggressively remove problem microbes, reshaping the whole microbiome into a more favorable configuration of populations. Fecal microbiota transplantation from a young donor to an old recipient will rejuvenate the balance of populations, and has been shown to produce health and longevity benefits in animal studies. The problem there is that it is unclear as to what exactly constitutes a beneficial microbe, and so it seems likely that fecal microbiota transplantation will be discarded in favor of culturing specific known mixes of microbes that can be delivered once via enteric capsules or similar to achieve a similar but more controlled outcome.
The gut microbiota and aging: interactions, implications, and interventions
Aging is associated with notable shifts in the composition and function of the gut microbiota. Research indicates a decrease in microbial diversity and changes in the abundance of specific bacterial groups in older individuals compared to younger counterparts. For instance, there tends to be an increase in Escherichia coli and other Proteobacteria and a decrease in beneficial bacteria like Bacteroides and Bifidobacterium, essential for gut health and overall wellbeing. Centenarians, a unique subset of elderly individuals, serve as a fascinating model for studying longevity and investigating gut microbiota alterations that could potentially facilitate healthier aging. Centenarians exhibit a noteworthy trend: an elevation in genera such as Akkermansia, which holds potential implications for longevity.
These alterations in the gut microbiota are influenced by several factors, including dietary changes, reduced physical activity, increased medication use, and physiological changes in the gastrointestinal tract such as decreased gut motility. The decline in beneficial bacteria and the proliferation of potentially pathogenic microbes contribute to an imbalanced gut environment, often referred to as dysbiosis. Dysbiosis in the elderly has been associated with various age-related conditions, like inflammaging, cognitive decline, neurodegeneration, insulin resistance, type 2 diabetes mellitus, cardiovascular disease, and cancer.
Given the critical role of the gut microbiota in aging and age-related diseases, there is a growing interest in microbiota-targeting interventions to promote healthy aging. In addition to dietary modifications, probiotics, non-viable probiotics (paraprobiotics), prebiotics, synbiotics, and microbial soluble factors (postbiotics) have garnered significant attention for their potential to modulate the gut microbiota and enhance the health of the elderly. Although still in the experimental stages for age-related conditions, fecal microbiota transplantation (FMT) has shown promise in restoring a healthy microbiota and improving metabolic and immune functions in older adults, based on animal studies.
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