Ageing is a natural process that leads to a decline in physiological functions. This decline increases the risk of diseases such as cancer, cardiovascular conditions, and neurodegenerative disorders. The gut microbiome plays a critical role in ageing by influencing digestion, metabolism, and immune responses. Over time, the diversity and composition of gut bacteria change, often leading to inflammation and metabolic imbalances that contribute to age-related diseases.
The gut microbiome is composed of trillions of microorganisms, including bacteria, fungi, and viruses, that interact with the host’s immune system and metabolism. In early life, gut microbiota diversity expands, reaching a peak in adulthood before gradually declining with age. This reduction in microbial diversity has been associated with increased frailty and susceptibility to infections. Understanding these microbial changes is crucial for developing interventions that promote healthy ageing.
Role of Fecal Microbiota Transplantation (FMT)
FMT involves transferring gut bacteria from a healthy donor to a recipient to restore microbial balance. Initially used to treat Clostridium difficile infections, FMT is now being explored for its potential benefits in ageing and age-related diseases. Researchers have found that microbiota from younger individuals may provide protective effects against inflammation, metabolic disorders, and cognitive decline.
Several studies in animal models have demonstrated that transplanting microbiota from young donors to older recipients results in improved gut integrity, enhanced immune responses, and increased lifespan. Conversely, transferring aged microbiota to young animals accelerates ageing symptoms, reinforcing the strong connection between gut bacteria and the ageing process. These findings have spurred interest in using FMT as a therapeutic intervention for age-related diseases.
How FMT Affects Longevity
FMT may influence longevity by modulating inflammation, metabolic health, and neurological function. Inflammation, often referred to as “inflammaging,” plays a central role in ageing and is driven by immune system activation in response to gut dysbiosis. By restoring a balanced microbiota, FMT can reduce inflammation and potentially slow down the ageing process.
Cognitive function also declines with age, partly due to changes in the gut-brain axis. FMT has shown promise in animal studies for improving memory and reducing neuroinflammation, which are key factors in conditions such as Alzheimer’s disease. Additionally, metabolic disorders like diabetes and obesity are linked to ageing and gut microbiota composition. Transplanting a healthier microbiome may enhance insulin sensitivity and regulate lipid metabolism, promoting overall health and longevity.
Preconditioning Donors for FMT
Enhancing the donor’s microbiome before transplantation may improve FMT outcomes. Some interventions that could optimise gut bacteria include:
- Caloric Restriction (CR): CR is one of the most studied anti-ageing interventions, known to extend lifespan in various species. CR alters the gut microbiota by increasing beneficial bacteria and reducing inflammation. FMT from CR-fed donors has shown the potential to improve metabolic health and delay age-related decline.
- Exercise: Regular physical activity has profound effects on gut microbiota composition. Exercise increases microbial diversity, enhances short-chain fatty acid production, and strengthens gut barrier function. FMT from exercised donors may contribute to better metabolic and immune health in recipients.
- Resveratrol Supplementation: This polyphenol, found in grapes and red wine, mimics caloric restriction benefits by activating longevity-related pathways. Resveratrol supplementation influences gut microbiota composition, increasing beneficial bacteria while reducing pro-inflammatory microbes.
- Metformin Treatment: Widely used for diabetes, metformin has demonstrated potential anti-ageing properties by modifying gut microbiota. Research suggests that FMT from metformin-treated donors could enhance glucose metabolism and reduce systemic inflammation in recipients.
- Spermidine Supplementation: Spermidine, a naturally occurring polyamine, has been associated with autophagy activation and longevity. Studies show that spermidine supplementation can remodel gut microbiota and improve metabolic health. FMT from spermidine-fed donors may help counteract age-related decline.
Challenges and Risks of FMT
Despite its promise, FMT carries certain risks, including infections and immune reactions. Donor selection is crucial, as an improper microbiota composition could negatively impact recipients. Regulatory guidelines vary across countries, complicating standardisation efforts. Advances in screening techniques and microbiome research are necessary to ensure the safe application of FMT for ageing-related interventions.
One of the main challenges is the complexity of microbiota-host interactions. The efficacy of FMT depends on factors such as the recipient’s baseline gut microbiota, immune system function, and lifestyle. Additionally, long-term effects of FMT on ageing remain unclear, necessitating further clinical research.
Another concern is the variability in donor microbiota composition. Some individuals may harbor particularly beneficial microbial communities, known as “super-donors.” Identifying these super-donors could improve the consistency and effectiveness of FMT outcomes. Researchers are also exploring the potential of “banking” young stool samples for future autologous FMT, allowing individuals to restore their own youthful microbiome later in life.
Future Perspectives
FMT could become a valuable tool in longevity research, but more studies are needed. Identifying optimal donors, refining transplant methods, and understanding long-term effects will be key to unlocking its full potential. Autologous FMT, where individuals store their own microbiota at a younger age for future use, is an emerging concept that could revolutionise personalised medicine.
Advancements in microbiome sequencing and artificial intelligence may also help in predicting the success of FMT for ageing-related applications. Personalised gut microbiota therapies, based on an individual’s microbial composition, could be developed to enhance precision medicine approaches for healthy ageing.
Conclusion
FMT offers exciting possibilities for extending healthspan by restoring a youthful gut microbiome. While challenges remain, continued research could lead to new therapies that harness the power of gut bacteria to promote healthy ageing. With further clinical validation, FMT may play a central role in future anti-ageing strategies, potentially transforming the way ageing is managed in medical science.
The study is published in the journal Ageing Research Reviews. It was led by Marta G. Novelle from Complutense University of Madrid (UCM).
