Juvenon Health Journal volume 9 number 7 july 2010
By Benjamin V. Treadwell, Ph.D.
Trillions of foreign microorganisms inhabit our body, both externally (skin, mouth, hair, ears, eyes) and internally (digestive system). Scary thought? Well, before you grab the disinfectant and head to the shower, read on.
For the most part, these organisms are harmless. They were actually instrumental in the evolution of the animal kingdom and have been with humankind since the beginning. Without them, we, as a species, might have withered away for lack of proper nutrition. So, we need to be aware of the benefits of treating these “foreigners” as welcomed guests.
The Essential Microbiome
In our digestive system, alone, there are several trillion bacteria (about 800 strains), which act on the foods we eat. Our bodies cannot absorb some foods (non-digestible plant fiber) until our gut bacteria, the microbiome, have digested them.
Some of these bacteria cross-feed. In other words, different strains are equipped with unique digestive machinery. Products of one strain can be further acted on by another to produce additional metabolites. The bacteria benefit us by producing many of the known vitamins (and probably some yet to be discovered) required for our health and survival.
So, the microbiome is really an accessory organ (like the pancreas and the liver) of the digestive system. And the relationship between the two is symbiotic; we need the bacteria and they need us. Naturally, how well this relationship functions is dependent on what we consume.
Recent research has confirmed the importance of including certain food types in our diets to maintain a healthy digestive system. This same research may have answered an even more basic question: how does the immune system allow bacteria to inhabit our digestive system in the first place?
Immune System Suppression
Scientists have speculated on this apparent contradiction for some time. The immune system establishes itself in virtually every tissue in the body, and for good reason. It protects us from pathogenic substances (toxins, viruses, some bacteria) and the diseases they can generate. So what protects the microbiome from the immune system?
Over the past several years, a number of reports have suggested that bacterial products, produced from fiber fermentation (acetate, propionate, butyrate), are probably the active agents in suppressing immune response in the digestive system. In other words, these bacterial-produced compounds function as signals that essentially say, “Hey, we’re your friends. Please don’t attack.”
However, the exact mechanism has been a mystery until now. A research team, from Medical College of Georgia and the Max-Planck Institute and University of Heidelberg in Germany, recently discovered that two of the bacterial products, propionate and butyrate, along with the immune system’s pre-dendritic cells are the keys.
Recognizing the Friendlies
The pre-dendritic cells are the sentinels of the digestive system, posted throughout the gut. Some of the bacteria we encounter in our environment are pathogenic and can cause many of those symptoms we have all encountered like diarrhea, fever, etc. This kind of foreign, dangerous intruder to the digestive system activates the sentinel cells and they begin developing into mature dendritic cells.
After reaching maturity, the dendritic cells start secreting potent inflammatory substances (cytokines, etc.), eventually leading to a full-blown immune system attack on the pathogen. Although this will kill the pathogen, in the process, it also causes collateral damage to the surrounding tissue, like swelling and production of excess amounts of fluid.
How do the beneficial bacteria avoid being attacked? The American and German researchers confirmed that they do produce specific substances from the foods they digest, which send the we-are-your-friends signal to the immune system, preventing the pre-dendritic cells from converting to the gung-ho fighters, the dendritic cells.
Furthermore, the research proved the theory that the bacterial substances were produced by fiber fermentation and identified the mechanism involved. Briefly, the good bacteria digest specific fiber and convert it to a number of compounds, two of which (propionate and butyrate) are transported into the pre-dendritic cells. Once there, they home-in on a specific gene-activating enzyme, histone deacetylase, and block its activity. This, in turn, prevents the pre-dendritic cell from converting to the inflammatory dendritic cell.
So, all is well. An immune system battle and associated unpleasant symptoms (swelling, diarrhea, etc.) are avoided and the friendly bacteria continue living a symbiotic relationship in our digestive systems. Unfortunately, this is not true for everybody, particularly those with fiber-deficient diets.
Genes and environmental factors both determine the health of our digestive system. Environmental factors, like too much sugar or alcohol or too many carbohydrates in our diet, can interfere with the proper activity of the system’s accessory organs, including the microbiome.
An unhealthy microbiome eventually leads to inflammation of the digestive system. Repeated bouts of inflammation compromise the integrity of the tissue, which can result in diarrhea, gastric discomfort and more serious health concerns.
Furthermore, the loss of integrity of the tissue may produce what is known as a “leaky gut,” allowing bacteria and their membrane constituents, lipopolysaccharides, to enter the blood stream, causing inflammation throughout the body. This may contribute to additional health concerns, such as atherosclerosis.
We were born with our genes and, for the time being, have little influence over them. But we can control the environmental factors – the foods we eat. Fiber has been shown to help prevent inflammation and its consequences. So diets that include high-fiber vegetables, fruits, legumes, nuts and whole grains, with minimal sugars and moderate amounts of alcohol, will be beneficial to our digestive systems.
Investigators, from the Medical College of Georgia and the Max-Planck Institute and University of Heidelberg in Germany, collaborated on an experimental protocol to examine the mechanism involved in preventing the production and activation of inflammatory cells in the colon. The team recently published their findings in “Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases” in The Journal of Biological Chemistry.
The researchers were aware of the enigma associated with the lack of an immune system response to the numerous bacteria harbored by the mammalian colon. Under normal conditions, the immune system recognizes bacteria as foreign and immediately activates a number of biochemical pathways, resulting in the production of a barrage of neutralizing and/or destructive responses (toxins, antibodies, scavenger cells). However, the bacteria residing in the digestive system are, for reasons now better understood, allowed to survive.
The investigators noted, from previous studies, that certain metabolites produced by these bacteria are beneficial to the health of the digestive system. Their experiments demonstrated that two of these metabolites, propionate and butyrate, were key to preventing the activation of the immune system and associated inflammation.
These metabolites enter the precursor dendritic cells, located in the colon tissue, and prevent the cells from developing into active dendritic cells. Because the active cells initiate the immune response, inhibiting their development allows the bacteria to continue their host-beneficial existence in the colon. In other words, the bacteria seem to be protecting themselves.
Perhaps another finding may be as important as defining the role played by propionate and butyrate in suppressing immune function and protecting beneficial bacteria. The researchers also demonstrated that these compounds are produced when the bacteria ferments (digests) particular fiber from the mammal’s diet. Treatment of disorders of the digestive system (ileitis and inflammatory bowel disease among others) that have been associated with fiber-deficient diets may benefit.
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.
Dr.Treadwell answers your questions.
question:Is this product (Juvenon) safe for people with type II diabetes? Will it raise or lower the blood sugars? Thank you. – L
answer:Acetyl-L-carnitine and alpha lipoic acid, the nutrients in Juvenon’s cellular health formula, help support overall good health and well-being. Since we have not initiated clinical trials, we cannot comment on whether taking the supplement will positively affect blood sugar levels. However, there is no reason to believe that individuals who may have diabetes cannot safely take Juvenon.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.