The composition of the gut microbiome is influential on health, perhaps to a similar degree as diet and exercise. Unfortunately this composition, the relative numbers of different microbial species, changes with age in ways that promote chronic inflammation and reduce the generation of beneficial metabolites necessary to tissue function. Researchers have shown that it is possible to rejuvenate an aged gut microbiome, producing a lasting reset to a more youthful configuration with a single intervention. Approaches include flagellin immunization to guide the immune system into destroying harmful microbiomes, and fecal microbiota transplantation from a young donor. While in principle one could achieve similar outcomes using tailored high dose probiotics, at this time available forms of probiotic therapy produce only short-term alterations to the gut microbiome.
In today's open access paper, researchers discuss fecal microbiota transplantation as an approach to treat aging as a medical condition. Adjusting the aged gut microbiome to a youthful configuration is a form of rejuvenation therapy, repairing a type of damage in order to remove the downstream consequences of this damage. Fecal microbiota transplantation from young donors to old recipients works well in animal studies, improving health and extending life. There is some use in human medicine, but the inability to completely control outcomes resulting from fecal microbiota transplantation suggests that the field will probably ultimately favor efforts to develop forms of analogous high dose probiotic therapy.
Fecal microbiota transplantation, a tool to transfer healthy longevity
The gut microbiome has emerged as an important contributor influencing host aging. The gut microbiome comprises an extensive population of microorganisms, predominantly different phyla of bacteria and, to a lesser degree, also viruses, protozoa, and fungi. Among other physiological roles, the gut microbiome supports the digestion and absorption of food, generates vitamins and nutrients, exerts a positive effect on lipid metabolism, maintains intestinal integrity, and metabolizes fibers into bioactive short-chain fatty acids (SCFAs), which have immunomodulatory, anti-inflammatory, and anti-cancer capabilities.
Microbe-derived SCFAs also play an important role in gut-brain intercommunication, with gut microbiota imbalances promoting brain alterations and neurodegeneration. Since these microorganisms play significant roles in immunological, metabolic, and physiological functions of host health, increasing evidence demonstrate that shifts in host-microbiome balance have a clinical impact in the pathogenesis of several metabolic disorders, age-related diseases, and other major conditions. In this scenario, personalized gut microbiome remodeling is evolving as a promising new era of therapeutic interventions against age-associated chronic diseases.
Interestingly, exceptional longevity of centenarians and semi-supercentenarians, who are less susceptible to inflammation, infectious diseases, and many other aging-associated dysfunctions, is also associated to the maintenance of a higher gut microbiome diversity of core microbiota species and a higher prevalence of health-associated gut-microorganisms compared to younger individuals. For example, Akkermansia muciniphila is present at higher abundance in centenarians. Conversely, progeria patients and progeroid mouse models exhibit a significant loss of this particular strain.
Gut microbiome from centenarians also presents high capacity for central metabolism, including glycolysis, amino acid metabolism and fermentation to SCFAs. Likewise, microbiome-related gene pathways related to bile acid metabolism - including secondary bile acid with antimicrobial activity - are suggestive of reduced levels of infections among centenarians. Furthermore, administration of A. muciniphila by oral gavage is sufficient to enhance healthspan and to promote lifespan in progeroid mice models, partially by the restoration of correct secondary bile acid metabolism and other metabolites (arabinose, ribose, inosine) in the intestinal tract of these animals.
Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. Throughout this review, we examine the impact of gut microbiome on host aging, and we address the potential therapeutic advantages of modulating gut microbiome via FMT. Preclinical and clinical research, along with current gaps, including safety and risks associated to FMT, are thoroughly examined. By addressing these objectives, this manuscript enhances our understanding of FMT-based interventions aimed at promoting healthier longevity.
View the full article at FightAging
