Interventions Targeting the Aging of the Gut Microbiome

Age-related changes to the microbial populations of the gut, the gut microbiome, appear important in the progression of aging. The effects on long-term health and risk of age-related conditions might be on a par with those of physical activity, and certainly overlap with those of diet. With ageing, beneficial microbes that produce metabolites (such as butyrate) that lead to better tissue function diminish in number, while harmful microbes that spur chronic inflammation grow in number. This may be due to loss of immune system competency, as the immune system gardens the gut microbiome, or it may be due to diminished intestinal barrier efficiency. Changes in diet characteristic of age may also play a role, but it is an open question as to the relative size of these and other potential contributing effects.

The research and medical community may not require a complete understanding prior to taking action, as it is quite clear from animal models that fecal microbiota transplantation from young to old reverses changes in the microbiome, improves health, and extends life span. Fecal microbiota transplantation is already practiced in human medicine, for conditions in which pathological bacteria overtake the intestine - conditions more commonly found in older people. Thus there is a comparatively short path to its use as a way to reverse ordinary, harmful age-related changes in the gut microbiome, given the will and funding to forge ahead.

Gut microbiota and old age: Modulating factors and interventions for healthy longevity

From a healthcare perspective, a longer life does not necessarily mean more health life-years. Unfortunately, aging often manifests itself negatively through frailty. Recent research has suggested that aging may be also associated with a different gut microbiota composition (i.e. a rearrangement) and with the increased presence of certain pathobionts, as compared to younger adults. This may be related to the heightened disease progression (and exposure to medication) and the decrease in immunocompetence in the older population. Most degenerative diseases are affected by our long-term dietary habits and lifestyle. Diet is also one of the most influential factors affecting our gut microbiota composition, diversity and function. Therefore, age-related dietary alterations could negatively impact the gut microbiota health in the older adults, and, consequently, their healthy longevity.

How aging affects the gut microbiota, the effects of the age-related changes on the health status of the host, and possible therapeutic approaches to counteract the negative aspects of dysbiosis have recently received considerable research interest. Although this research area has been expanding tremendously over the past years, there are still major gaps in our understanding of the functional interactions between the complex microbial community and the human host, especially at an advanced age. For example, which are the main factors which negatively influence our gut microbiota diversity and functions? Are they different in the older population as compared to younger adults? Are there specific microbiome signatures for longevity or are they rather reflective of health status? Are short-term effects (e.g. antibiotic exposure) as important as the long-term ones (e.g. food preferences), and which ones are more difficult to counterbalance? Are therapeutic interventions targeting the gut microbiota less effective or less safe in the older adults? Are these interventions suitable for entire populations, or should they be targeted individually (i.e. personalized modulation of the microbiota)?

Over the past two decades, numerous randomized clinical trials have been conducted in various target populations, including the older adults, to investigate the effectiveness of several therapeutic approaches impacting out gut microbiota and improving our health. Among these, supplementation of the human diet with beneficial microorganisms (probiotics), substrates to promote the proliferation of these beneficial microbes (prebiotics), or a combination of both (synbiotics) represent the most investigated health interventions.

Based on the results of several randomized clinical trials showing fecal microbiota transplantation (FMT) as a viable alternative treatment approach against C. difficile infection, current clinical guidelines recommend FMT for "patients with multiple recurrences of C. difficile infection who have failed appropriate antibiotic treatments (strong recommendation, moderate quality of evidence)". C. difficile infection is known to affect the older population disproportionately, mainly due to immunosenescence, increased exposure to healthcare settings, and frequent use of antibiotics and proton-pump inhibitors. FMT proved to be a safe and effective treatment option for C. difficile infection in older adults.

Following the success in C. difficile infection treatment, the potential of FMT has also been investigated against Crohn's disease, irritable bowel syndrome, cirrhosis, and even neurological and behavioral conditions. The results are promising, but still modest. One important aspect in the success of FMT is the diversity and the composition of the stool donor, which plays an essential role in restoring metabolic deficits in recipients.

Our gut microbiota is a dynamic ecosystem, which adapts continuously to changes in lifestyle, nutrition, hygiene, and exposure to medication. Establishing and maintaining positive interactions between us and our gut microbiota are essential for our health. The longer the exposure to certain stressors, the more significant the changes, which may explain why recent research has found that older populations have a less diverse microbiota than younger individuals, and more pathobionts. With advanced age, the prevalence of certain diseases increases as well, which can also contribute to an increased risk of frailty leading to microbiota dysfunctionalities, and therefore, to progression of other metabolic diseases.

Regarding older adults, and especially the residents of long-term care facilities, microbiota-targeted interventions should be made early and often, to attenuate the occurrence of critical conditions such as frailty. Any long-term medication exposure, and especially antibiotic treatments, should be followed by a microbiota restoration therapy, to prevent the occurrence of dangerous infections such as C. difficile and the proliferation of other opportunistic strains.

Comments

Unfortunately almost all research on this is being done outside the US and Europe. I suspect big Pharma is actively waging a campaign to smear FMT.

Posted by: JohnD at October 19th, 2020 7:56 PM

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