Reviewing the Links Between the Gut Microbiome and Frailty

Age-related frailty has a strong inflammatory component. The chronic inflammation of aging is disruptive of tissue function and over time contributes to the loss of muscle mass and strength characteristic of frailty. Some fraction of that chronic inflammation is the consequence of changes in the gut microbiome, the loss of helpful populations and the expansion of harmful, inflammatory populations of microbes. The relationship between age-related changes in the gut microbiome and the age-related decline of the immune system into a state of chronic inflammation is likely bidirectional, but it has been shown that fecal microbiota transplantation from young to old animals improves the situation. This approach should be tested in humans.

As the population ages, frailty syndrome will bring a huge medical burden to society. Previous studies have suggested that gut microbiota imbalance may be a cause of frailty. Animal models and a few human studies have demonstrated that individuals with frailty tend to have increased levels of inflammatory factors (e.g. IL-6, C-reactive protein, and TNF-α) and a chronic inflammatory status. Inflammatory factors have been demonstrated to directly or indirectly reduce key indicators of frailty, such as muscle mass and grip. In addition, gut microbiota imbalance has been demonstrated to be associated with higher expression of inflammatory factors.

Studies have suggested that gut microbiota imbalance leads to enhanced intestinal permeability. This in turn triggers the entry of pathogen-related antibodies like PAMP and DAMP to the circulatory system to subsequently trigger an inflammatory reaction. As a result, investigators believe that the chronic inflammatory status due to gut microbiota imbalance could directly or indirectly give rise to the typical symptoms of frailty (by causing cardiovascular diseases or damaging the musculoskeletal system). In addition, higher levels of inflammatory factors due to gut microbiota may further influence the nervous system of the host via the gut-brain axis to induce neuroinflammation leading to neurodegenerative diseases, i.e., dyskinesia and/or cognitive disorders in patients with frailty.

However, the above assumptions have not been validated in large cohort-based studies. The relationship of gut microbiota imbalance, chronic inflammation, and frailty is not unilateral but complicated and interrelated. Several studies have suggested that chronic inflammation due to gut microbiota imbalance may not be the only cause of frailty. It is worth noting that individuals with frailty are on long-term medication due to preexisting chronic diseases. It has been demonstrated that medications could alter gut microbiome composition. Hence, future studies are necessary to determine whether gut microbiota is a cause of frailty or a result of long-term medication in people with frailty. In addition, factors that may affect the gut microbiota, such as lifestyle, diet, and other health complications, need to be considered comprehensively.


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