If Probiotics in their Present Form Were a Truly Effective Intervention, We Would Already Know

There is an increasing focus in the research community on the role of the gut microbiome in aging. This is in large part driven by the ability to accurately, cost-effectively measure the composition of the gut microbiome from a stool sample, using 16S rRNA sequencing. The 16S rRNA gene is differs between bacterial species, without being subject to a high rate of mutation and change. Using low-cost modern techniques, researchers can thus read out the relative numbers of different species in the gut microbiome, a service now available to the public at large as well. This allows researchers to see exactly how the balance of populations changes with age and disease states.

The gut microbiome does change with age, and it changes in ways that promote harmful, inflammatory microbial populations at the expense of helpful microbial populations responsible for generating beneficial metabolites such as butyrate. Researchers have shown that transplanting a microbiome derived from stool samples from young animals into old animals can reset the aged microbiome to a more youthful balance of microbial populations. The result is improved health and extended life.

Unfortunately, when it comes to the application of this discovery to human medicine, all too often the focus stops at the application of probiotics to the problem of the aged metabolism. Yes, we know that probiotics are beneficial. Yes, they are cheap and readily available. If present probiotic formulations were a truly effective intervention, capable of restoring a youthful gut microbiome, we would certainly know that by now. Alas, they are not. Given the evidence to date from animal studies, the real focus should be on establishing the infrastructure for widespread us of fecal microbiota transplantation from young donors to old people.

Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time?

Aging is characterized by increased concentrations of many pro-inflammatory factors in the circulation. In addition, chronic low-grade inflammation has been identified as a key process involved in aging. Chronic low-grade inflammation is influenced by changes in different tissues (muscle, adipose tissue), organs (brain, liver), systems (immune system), and ecosystems (gut flora). It can indirectly trigger diseases in other organs (e.g., metabolic diseases, neuroinflammatory diseases, cardiovascular diseases, etc.). Chronic low-grade inflammation is one of the main contributing factors to various age-related diseases in the elderly.

Furthermore, chronic low-grade inflammation is closely related to the dysregulation of gut flora. Many immune cells and microbiota in the digestive tract interact with each other to maintain immune homeostasis. Intestinal microbiota plays a role in maintaining healthy levels of inflammation by integrating gastrointestinal, immune, and neurological information. Data obtained from animal models have demonstrated that age-related microbial ecological disorders can lead to intestinal permeability, systemic inflammation, and premature death. Altering the gut microbiota of older adults with wholesome bacteria exerts positive effects on the maintenance of optimal immune responses, which decline with age. Such effects include delaying the aging of T lymphocytes and increasing the number of immune cells that respond to acute antigen exposure.

Probiotics can effectively assist in maintaining the balance in the composition of gut microbial flora, thereby protecting the gut barrier and regulating gut immunity. Increasing scientific evidence has shown that probiotics exert a positive effect on chronic low-grade inflammation and play a key role in healthy aging and improving age-related diseases. Probiotics might be an important therapeutic strategy for the prevention, delay, or even reversal of low-grade inflammation in old age. However, robust controlled clinical trials are warranted to further validate this hypothesis.