Fight Aging!

The balance of microbial populations making up the gut microbiome is now known to change with age in ways that promote chronic inflammation. There are more inflammatory microbes passing the intestinal barrier to enter tissue, and more microbes capable of generating harmful metabolites that aggravate cells. The aging of the microbiome is only loosely connected to the aging of the body, however. Animal studies make it clear that the gut microbiome of an old individual can be restored to a youthful balance of populations via fecal microbiota transplant from a young individual, benefits to health and longevity result, and that one intervention lasts for a long time.

It is in principle possible to achieve the same result as a fecal microbiota transplant using probiotics, given a large enough sustained dose. In practice, that cannot yet be accomplished, however. The right balance of species would have to be manufactured, and present probiotic manufacture is limited to a very small number of microbial species in comparison to what one finds in the gut microbiome.

Even given the point that one or two of the species known to lose abundance with age might be capable of delivering enough of a benefit to be worth it, even if only a fraction of that produced by fecal microbiota transplant, the actual result of present probiotic treatment, the products one can purchase in a store, appears to be at best a comparatively small, short-lived benefit. Still, given what is presently known of the impact of the gut microbiome on health, and how to rejuvenation an aged gut microbiome, it seems likely that probiotics will become a good deal better in the years ahead.

Can probiotics mitigate age-related neuroinflammation leading to improved cognitive outcomes?

Systemic inflammation, which leads to neuroinflammation, is likely a risk factor for the progression of neurodegenerative diseases. Although systemic inflammation can be the result of numerous processes and diseases, one key trigger during aging is changes in the gut, such as the increase in gut permeability and alterations in microbiota composition. During aging, the gut naturally becomes more permeable. The gastrointestinal tract is the second largest interface between the host and the outside world. Therefore, this reduction in its barrier function associated with aging has follow-on consequences, such as allowing unwanted components (antigens and opportunistic pathogenic bacteria) to enter the body, leading to the production of proinflammatory cytokines in the blood. These cytokines can then cross the blood brain barrier to cause neuroinflammation, which impacts brain function.

Whether age-associated increases in gut permeability are a cause or a consequence of other gut related changes is currently unknown. However, a recent study showed that the development of gut barrier dysfunction during aging is not consistent across all people. People with irritable bowel syndrome (IBS) are more susceptible to gut hyperpermeability in later life than healthy individuals. Interestingly, those with IBS are also more at risk at developing Alzheimer's disease (AD), supporting the idea that gut hyperpermeability is a risk factor for AD.

Recent studies have sought to define a microbiota profile associated with healthy aging, but this varies between the study populations. However, gut microbiota composition of people with AD has been shown to differ from that of healthy older adults in a number of studies. Recent studies have also shown there is a difference in the composition of the gut microbiota between people with mild cognitive impairment (MCI) and those without, and that these differences are similar to those seen in people with AD. This implies that microbiota dysbiosis proceeds AD development and, therefore, may be a driver in the disease progression.

It therefore follows that treatments that can maintain healthy gut function may reduce inflammation and protect against, or improve, symptoms of age-associated neurodegeneration. The aim of this mini-review was to evaluate whether probiotics could be used for this purpose. A search resulted in 187 papers describing primary research on probiotic intervention with older adults. A review of this research concluded that there is preliminary evidence to suggest that specific probiotics may improve cognitive function, particularly in those with MCI; however, this is not yet convincing and larger, multilocation, studies focus on the effects of probiotics alone are required. In addition, studies that combine assessment of cognition alongside analysis of inflammatory biomarkers and gut function are needed. Immense gains could be made to the quality of life of the aging population should the hypothesis be proven to be correct.