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.

Comments

Not really sure how much probiotics do for the middle age and elderly. My own experience seems to be they help keep Candida in check at least.

Posted by: Mike Best at June 26th, 2023 5:22 PM

For some time now I have been reading fa! through its posts' and its comments' RSS feeds with Thunderbird. It provides a ToC ( Table-of-Contents ) for the posts, and you can build a month / year [ / decade :) ] ToC tree. ( Is there a way to get the whole archive RSS ...'dump' [?], in order to populate my fa! account 'cache' on my computer ? Because for now I can only build this ToC as new RSS 'elements' arrive. The only other solution I have found for archive-months before I started collecting the RSS feed elements is google. com/search?q=headingsmap Firefox and Chrome extension. )

Getting back to functionality, you can star posts and comments of personal interest, and then use the sorting function on comments poster name to identify interesting commenters. You can then use search engines' domain restriction ( e.g. "site:" for Google ) to find all the comments from that commenter.

I am doing this because our 'fight' is highly 'disruptive', and some subjects can not be commented publicly ( like the subject of the present post ). I think it is paramount for each of us to find out other commenters who live nearby, and form IRL communities to discuss IRL the more disruptive aspects of our fight. So here is such a 'finding place' for my "closest [metro]politan area" :

facebook. com/groups/fightaging. org. fans. paris

( It is very important that these groups 'mitose' when they reach about ~50 members ).

Posted by: BenoƮt ( Paris, France ) at June 27th, 2023 4:22 AM

They for sure are proven to help of you have genuine care of dysbiosis (aka dysbacteriosis) , usually after taking antibiotics. And sometimes can help fight bad bacteria/fungi at check. I would guess that in cases of damaged intestine walls or weaker brain blood barrier that could add up to quite a difference in health outcome.

For now only senolytics and stem cell transplants can beat or at least need in synergy with good old calorie restriction

Posted by: Cuberat at June 27th, 2023 10:42 AM

These two sections above seem to directly contradict one another. The top part states, "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."

While the bottom section states: "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."

Can you help resolve this contradiction?

Posted by: Saurabh Gupta at July 1st, 2023 5:18 PM

Saurabh Gupta:

Only the author can explain what they meant but here is my interpretation. It appears to me that the author is suggesting that Probiotics cannot restore an aging microbiome to a more youthful state, The author is suggesting fecal transplants might be more successful in that endeavor.

The author appears to be stating that probiotics may have some benefits (balancing of flora, gut immunity). However, the author also appears to be implying that these benefits are not robust enough to be considered as bringing the microbiome back to a more youthful status.

Posted by: Brad at July 2nd, 2023 12:56 PM

Eating resistant starches probably provides more benefit to the gut microbiome than probiotics do. It is the path I have chosen.

Posted by: TB at July 7th, 2023 4:44 AM
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