Manipulation of GI bacteria for our health using the essential sugar, fucose

Hi everyone,

In postings to the Calorie Restriction Society I have mentioned the anti-cancer effect of butyrate. Prior postings have shown it to suppress appetite also. Butyrate is produced by GI bacteria digesting (fermenting) resistant starches. Of these bacteria, Roseburia sp., are some of the most productive of butyrate.

For example, (1) points out that Roseburia inulinivorans is up-regulated by the essential sugar, fucose. What is fucose? It is a very interesting sugar which appears little appreciated in human health (2).

Read the end of (2) to see the role that Bacteroides thetaiotaomicron (BT) plays with fucose. Not only is fucose in food but it is actively produced by our intestinal linings on request by BT. Without this bacteria we will not actively produce fucose. BT is one of the most abundant bacteria in our colon so unless you've been on antibiotic therapy recently you should have plenty of this bacteria.

Fucose is in the supplement Fucoidan and is from brown seaweed. There are several hundred published articles on the health and longevity enhancement effects of fucose/Fucoidan. See (3, 4) for more.

If you're in an experimental mood consider (5). BT requires ammonia to grow well. Our bodies produce ammonia from protein metabolism and then we excrete it via our urine with most of it in the form of urea. I wonder what might happen if we were to give BT some ammonia directly? For example, (6) tells how to make ammonia cookies. Will this really increase the amount of fucose we produce? I have no idea. It simply seems something fun to try. I've never had ammonia cookies.

1. J Bacteriol. 2006 Jun;188(12):4340-9
Whole-genome transcription profiling reveals genes up-regulated by growth on fucose in the human gut bacterium "Roseburia inulinivorans".
Scott KP, Martin JC, Campbell G, Mayer CD, Flint HJ.
Gut Health Division, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, United Kingdom. K.Scott@rowett.ac.uk
"Roseburia inulinivorans" is an anaerobic polysaccharide-utilizing firmicute bacterium from the human colon that was identified as a producer of butyric acid during growth on glucose, starch, or inulin. R. inulinivorans A2-194 is also able to grow on the host-derived sugar fucose, following a lag period, producing propionate and propanol as additional fermentation products. A shotgun genomic microarray was constructed and used to investigate the switch in gene expression that is involved in changing from glucose to fucose utilization. This revealed a set of genes coding for fucose utilization, propanediol utilization, and the formation of propionate and propanol that are up-regulated during growth on fucose. These include homologues of genes that are implicated in polyhedral body formation in Salmonella enterica. Dehydration of the intermediate 1,2-propanediol involves an enzyme belonging to the new B12-independent glycerol dehydratase family, in contrast to S. enterica, which relies on a B12-dependent enzyme. A typical gram-positive agr-type quorum-sensing system was also up-regulated in R. inulinivorans during growth on fucose. Despite the lack of genome sequence information for this commensal bacterium, microarray analysis has provided a powerful tool for obtaining new information on its metabolic capabilities.
PMID: 16740940

2. http://www.innvista.com/HEALTH/nutrition/essensug/fucose.htm
Functions
It is now known that Fucose glycoconjugates (glycoproteins and glycolipids) are an essential part of eliminating or reversing such disease processes as cancer, inflammation, and immunity.
Fucose concentrations are found in such areas as:
a) at the junctions between nerves, implying that a deficiency could affect synaptic transmissions;
b) in the proximal tubules of the human kidney, indicating the vital need for this saccharide for proper kidney function;
c) in the testes, suggesting that it plays an important role in reproduction;
d) in the outer layer of skin, where it may be involved in maintaining skin hydration.
Fucose is profoundly important for efficient neuron transmission in the brain. According to studies, Fucose is known to influence brain development and may also help improve the brain’s ability to create long-term memories. Several studies have shown that, by inhibiting the Fucose-containing protein, amnesia developed. Research is ongoing but showing good promise.
Fucose is a powerful immune modulator. It is distributed in macrophages, which are critically important to immune function. There have been numerous well-documented benefits for its necessity in immune function ,especially that of an overactive immune system, the cause of autoimmune disorders. Fucose is showing promise in its ability to normalize immune function.
Fucose is particularly active in inflammatory diseases and has the ability to suppress such allergic skin reactions as contact dermatitis.
Fucose and another essential sugar, Mannose, have the ability to kill bacteria and to help fortify resistance to infection. This is particularly true of respiratory cells. New studies reveal that, because bacteria have lectins on their surfaces that stick to the host’s saccharide receptors, supplying the body with these essential sugars can help deflect host-binding so that an infection can either be foiled or lessened.
Researchers who injected Fucose into lab animals found a possible treatment for breast cancer. U-fucoidan, a complex polysaccharide found in brown seaweed, was able to kill cancer cells in vitro within 72 hours. Interestingly, the destruction was self-induced (apoptosis), suggesting that the sugars were able to break down the DNA within each cancer cell through enzyme action.
Fucose can be found in blood cell antigens, which are involved in determining blood type.

Cancer
Fucose studies are also showing that it plays a significant role in many diseases, including cancer and its spread. Research is still ongoing but showing promise in the areas of inhibiting and reversing leukemia and breast cancer, including the suppression of tumor growth. Some studies have concluded that Fucose and Mannose appeared to be the most effective of the essential sugars when it came to slowing the growth of cancer cells.

Rheumatoid Arthritis
Levels of Fucose are low in those with rheumatoid arthritis, and supplementation is showing promise as a harmless but surprisingly effective treatment. What is particularly interesting is the lower a person’s level of Fucose (as well as Galactose, another essential sugar), the more advanced the disease.

Other Diseases
Fucose metabolism appears to be altered in various diseases. Several studies have concluded that Fucose metabolism is abnormal in those with cystic fibrosis, diabetes, and during episodes of shingles, which is caused by a herpes virus. These studies go on to suggest that the sugar is active against other herpes viruses. In addition, the saccharide guards against respiratory tract infections and inhibits allergic reactions. Liver function and serum protein levels were also affected by a deficiency of Fucose. All these disorders, as well as many others, go back to immune function where fucose is showing to play a significant role.

Future Use
In other studies, Fucose proved that it can be incorporated into certain areas of the body where and when it is most needed. For instance, Fucose incorporated into the photoreceptor layer of the retina, may help with the biosynthesis of rod cell glycoproteins. In psoriasis, fucose may play a significant role in the disease process because of altered glycoprotein distribution. Normally, skin keratinocytes and non-psoriatic cells have most of their fucose on the plasma membrane, whereas psoriatic cells retain most of their fucose within the cytoplasm. The list is endless for connecting the reversal and prevention of disease and the use of Fucose and other essential sugars.
Out of the 400 or so species of intestinal microbes found in the human intestine, one has been studied as being of particular interest in its relation to Fucose – Bacteroides thetaiotaomicron. Present from birth, this bacterium survives in the lower part of the gut and feeds on Fucose. Cells lining the intestine manufacture it and post it on the surface of the cell. During weaning, Fucose production stops but begins again if B. thetaiotaomicron is present, leading researchers at Washington University School of Medicine to conclude that the bacterium is able to communicate to the intestine that it requires Fucose for its food. Understanding this communication between microbes and human cells may help provide treatment when friendly intestinal bacteria are destroyed after the use of antibiotics, for instance.

3. http://www.nutraingredients.com/news-by-health/productpresentation.asp?id=382&k=jinke-gingko-fucoidan
Fucoidan for a Healthy Life
04/1/06 - Jinke Group USA Inc, as the Subsidiary of Beijing Gingko Group announced a new product Ginnovay Fucoidan to the market. Ginnovay is the Trade Mark of BGG

BGG is leading the way to provide a potential natural non-toxic holistic healing product, Fucoidan, to support the body ability to forestall a lot of health problem, reported by Dr. Jay Lee in Jinke Group USA Inc.

Fucoidan is a type of glyconutrient as a new and more specialized type of nutraceutical. The main effective ingredient in Fucoidan is the fucose, one of the eight essential biological sugars. Since 1996, a total of four Nobel Prizes in medicine have been awarded for work in glycobiology. Unlike other nutritional supplements, Fucoidan provide special saccharide, biological sugars, which have recently been identified as being absolutely essential for cell-to-cell communication through glycoproteins and glycolipids.

Typically only glucose and galactose are in the foods we eat so we don’t consume Fucose and must produce over thirty-four different enzymatic reactions to generate intermediate molecules to make Fucose. During the conversion process if there is any problem in any step (due to toxins, stress etc) it will cause a severe and chronic disease. Now there are evidences that people in Japan who consume large quantities of these seaweeds (Fucoidan) have the longest lifespan.

Fucoidan produced by BGG is extracted from two brown seaweeds, Cladosiphon okamuranus grown in Japan and Ascophyllum nodosum from Norway.

4. http://limu.icthus.net/fucoidan.shtml
Excerpts from the book: Fucoidan
Fucoidan, The Ocean's Gift: Many people don’t fully understand the extreme importance of controlling free radical cellular damage in the body. A free radical is an unstable oxygen molecule that must find another electron to make itself complete. In order to do this, the free radical begins randomly bombarding the body’s cells, resulting in injury to the surrounding cell tissue.

The damage from free radicals can be countered by antioxidants. Antioxidants stop free radical damage by donating an electron without becoming a damaging free radical themselves. The problem in today’s society is that because of the lack of proper nutrition and moderate exercise, the number of free radicals in our bodies vastly outnumbers the number of antioxidants. This leads to premature aging and chronic disease.

The answer to this dilemma is to supplement our diets with plant-derived substances that contain antioxidants. However, not all supplements are made the same. Some supplements contain mostly filler or they contain impure plant products. Sometimes, the plants from which the supplements are made were grown in soil that lacks the necessary vitamins and minerals to create a plant rich in antioxidants. Again, Limu Moui does not suffer from soil deficiencies. It contains the antioxidants necessary to help prevent the negative effects sustained from free radical damage. Researchers in Madrid, Spain, showed that ingredients in brown seaweed exhibited great capacity as a natural antioxidant-even greater than extracts from green and red sea plants.

Fucoidan in Limu Moui
Limu Moui has been a vital source of food and commerce for many coastal peoples. Not surprisingly, some of these people credit the plant for their long lives. Many Tongans, for instance, stay robust, full of life and vigor, without suffering the effects of disease normally associated with aging. If you were to ask for their secret, chances are the Tongan people would direct you to Limu Moui as the reason for their good health.

In Japan, sea plant dishes like kombu and wakame are well known, but a lesser known dish call mozuku shares a common characteristic with Limu Moui. The people in the regions of Japan where mozuku is used enjoy longer lives and lower incidences of cancer when compared to counterparts in other parts of Japan.

Recent studies actually verify these phenomenona. Japanese scientists have isolated a substance in Limu Moui that promotes healthy living, seems to slow down the aging process, and fights a myriad of diseases. This substance is called fucoidan. A large number of recent scientific studies have shown fucoidan fights against cancer formation, development, and growth. Other research also indicates that fucoidan can be used for many other ailments common in today’s world.

5. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=186696
Appl Microbiol. 1974 August; 28(2): 251–257.
Nutritional Features of Bacteroides fragilis subsp. fragilis
Vincent H. Varel and Marvin P. Bryant
Departments of Dairy Science and Microbiology, University of Illinois, Urbana, Illinois 61801
Studies of three reference strains of Bacteroides fragilis subsp. fragilis showed that they grow well in a minimal defined medium containing glucose, hemin, vitamin B12, minerals, bicarbonate-carbon dioxide buffer, NH4Cl, and sulfide. The vitamin B12 requirement of 0.1 ng/ml was replaced with 7.5 µg of methionine. Cysteine or sulfide was an excellent source of sulfur, thioglycolate was a poor source, and thiosulfate, methionine, ß-mercaptoethanol, dithiothreitol, sulfate, or sulfite did not serve as sole sources of sulfur. Neither single amino acids, nitrate, urea, nor a complex mixture of L-amino acids or peptides effectively replaced ammonia as the nitrogen source. Comparative studies with a few strains of other subspecies of B. fragilis including B. fragilis subsp. vulgatus, B. fragilis subsp. thetaiotaomicron, and B. fragilis subsp. distasonis indicate that they exhibit similar growth responses in the minimal medium. A single strain of B. fragilis subsp. ovatus required other materials. The results indicate the great biosynthetic ability of these organisms and suggest that, in their ecological niche within the large intestine, many nutrients such as amino acids are in very low supply, whereas materials such as ammonia, heme, and vitamin B12, or related compounds, must be available during much of the time.

6. http://www.emerils.com/recipes/by_name/ammonia_cookies.html
AMMONIA COOKIES
from Cooking Section, September 2001

Ingredients needed:

1 cup milk
One-half ounce ammonium carbonate
One-half cup shortening
One and one-fourth cups sugar
1 egg, well beaten
One-half ounce oil of lemon or 1 ounce lemon extract
5 cups sifted enriched flour

Preheat the oven to 350°F.

Add the milk to the ammonium carbonate and let stand for 30 minutes, stirring frequently. Cream the shortening and the sugar; add the egg, lemon flavoring and the milk mixture. Stir in the flour. Chill. Roll the dough to one-fourth-inch-thick on a floured board. Cut into 3-inch squares. Prick with a floured fork. Bake on a greased baking sheets at 350 degrees for 15 minutes or until slightly browned.

Note: Ammonium carbonate is no longer readily available in stores. It can be special-ordered by many druggists, and sells for about $1.75 an ounce. Commercial bakeries use ammonium carbonate as a dry rising agent for various products, and may be willing to sell small batches to the public on request.

Makes three and one-half dozen.


Nerissa