Targeting the Gut Microbiome to Treat Aging

The distribution of microbial populations making up the gut microbiome changes with age in ways that are harmful to health, causing a reduction in production of beneficial metabolites and an increase in chronic inflammation. Animal studies make it clear that some approaches to restoring a more youthful gut microbiome, such as fecal microbiota transplantation from young donors, can produce a sustained rejuvenation of the gut microbiome and consequent improvement in later life health. Given the comparatively simplicity of this approach, and that the state of the gut microbiome can accurately measured via low-cost assays, this seems a cost-effective, near-term approach to the treatment of aging.

The link between human health and the gut microbiome is profound and has been speculated upon for thousands of years. In 400 B.C., it was suggested by Hippocrates that "bad digestion is the root of all evil" and "death sits in the bowels". It is now well-known that humans are inhabited by microorganisms, including bacteria, viruses and archaea, that live in harmony with them. Many aspects of human health are also influenced by the gut microbiota, as they may provide energy and nutrients to the host by aiding the digestion of nondigestible dietary components and can also contribute to inflammation, infection, gastrointestinal diseases, diabetes mellitus, and obesity. Interestingly, the composition of the human gut microbiota shifts with age, leading to influenced changes in the host's health. In this regard, the disturbance of the microbiome has been suggested as a new hallmark of ageing.

Diet can be used to modulate the composition of gut microbiota. An abundance of short-chain fatty acids, which are produced by gut microbes and have been shown to exhibit protective roles against a panoply of diseases, has been shown to correlate with diet. It was shown that as compared to an animal-based diet, vegan and vegetarian diets which comprise greater intake levels of fibre, resulted in higher levels of short-chain fatty acids. Interestingly, calorie restriction is known as the only experimental procedure that can, in various animal models, effectively lengthen lifespan. In a study that studied the shift in gut microbiota induced by a high-fat diet versus a low-fat diet in mice, it was demonstrated that mice with a 30% restriction of low-fat diet had a unique gut microbiota, indicating that modulation of the gut microbiota can be achieved by restricting the intake of diet.

Prebiotics - nondigestible food ingredients that are metabolized by selective intestinal microorganisms - can be used to modulate the gut microbiota to increase the abundance and activities of beneficial bacteria. Prebiotics resist digestion in the small intestine to reach the colon, where they are acted upon by gut microflora, leading to specific changes in composition and activity in the gut microbiota. Probiotic supplementation has been applied in the modulation of the gut microbiota to convey health benefits. Probiotics are defined as live microorganisms that confer to improve the health of the host when adequate amounts are administered in a safe and efficacious manner. Several studies have supported the use of probiotic supplementation for its therapeutic effects against a broad range of diseases, especially for metabolic and gastrointestinal disorders. In addition, the ability of probiotic supplementation to modulate the gut microbiota was reported in terms of faecal bacterial community structure being significantly different as compared to placebo.

Faecal microbiota transplantation is the administration, into a recipient's intestinal tract, of the whole microbiota from healthy donor faeces to modify or normalize intestinal microbiota composition. The ability of faecal microbiota transplantation to treat several diseases, including irritable bowel syndrome, metabolic diseases, autoimmune diseases, constipation, neuropsychiatric conditions, colon cancer, chronic fatigue syndrome, and allergic disorders, has been reported. The ability of faecal microbiota transplantation to treat Clostridioides difficile infection in the elderly (85 years old and above) was recently investigated, and the report indicated that severe infections in all cases were improved following one faecal microbiota transplantation, indicating that "frail older people" might benefit from faecal microbiota transplantation.

It is now clear that the age-related dysbiosis of the gut microbiota may lead to unhealthy ageing, contribute to the development of comorbidities and may even dictate the lifespan of individuals, as shown in the previous sections. Hence, by inducing changes in the gut microbiota, it might be possible to improve the health of the elderly and even prolong their lifespan.


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